The Sepsis is caused when the body's immune responses against a life threatening condition infection harm's own tissues and organs. It is one of the most serious complications of infectious diseases caused by bacteria , viruses , fungi or parasites. The most common sources of infection in sepsis include pneumonia , infections of the gastrointestinal and urogenital tracts , as well as infections of skin and soft tissue, the central nervous system and so - called catheter-associated infections. Sepsis must be treated as an emergency.
Sepsis or a septic disease occurs when the body's own defense systems can no longer limit an infection and its consequences locally. There is an excessive defense reaction of the body, which damages its own tissue and organs. If the sepsis is not recognized and treated in time, this can lead to multiple organ failure and / or septic circulatory shock and can be fatal. Common symptoms are fever, mental changes, heavy, rapid breathing, high heart rate, and feeling very sick. However, newborns, the very elderly, and people with weakened immune systems may have sepsis without any obvious signs of infection, and body temperature may be normal or low. Premature babies and newborns, people of older age and people with a weakened immune system due to chronic diseases, diabetes mellitus, cancer or HIV have an increased risk of sepsis.
The intensive care , by temporary replacement or support of the organ functions ( breathing , renal replacement therapy , circulation therapy , coagulation therapy bridge critical phases). Nevertheless, about 25% of patients with sepsis and 45% of patients with severe sepsis die under maximum therapy. Starting therapy as early as possible is crucial for survival.
Sepsis is one of the most common and cost-intensive diseases in the inpatient sector. The World Health Organization (WHO) therefore declared the disease to be one of the leading priorities in the health systems of the member states in 2017 in order to improve the prevention, diagnosis, therapy, recording and aftercare of sepsis patients.
To the subject
The word "sepsis" comes from the ancient Greek σῆψις sēpsis ("putrefaction" or "fermentation"). The term septicemia , which was previously used synonymously, has not been used since 1991 due to the vague definition. The term bacteremia , which is sometimes used synonymously, is out of date and does not correspond to medical reality, since only about 30-40% of sepsis are associated with bacteremia. The term " blood poisoning " is not defined and is not used in technical terms.
According to an older definition (by Hugo Schottmüller and Konrad Bingold , 1925), sepsis occurs “if a focus has formed within the body from which pathogenic germs constantly or periodically enter the bloodstream in such a way that this invasion subjective and objective symptoms are triggered ”.
In 2015, 75,000 sepsis deaths were documented in Germany. That is more deaths than those from lung, colon, breast and prostate cancer combined. Sepsis was present in around 15% of the patients who died in hospital in Germany in 2015. However, these estimates are still rather underestimated: Recent studies show that less than 50% of patients with sepsis identified on the basis of patient records are in the official registers prescribed by the World Health Organization (WHO) ( International Classification of Diseases, ICD-10 ) documented to record the burden of disease.
The incidence of illness determined on the basis of hospital discharge diagnoses for Germany results in 370 cases of sepsis per 100,000 inhabitants for 2015, of which approx. 158 meet the criteria for severe sepsis. The extrapolations based on the entry in the medical records, however, result in significantly higher case numbers. In the US, this is 517 per 100,000 population. That equates to 1.67 million illnesses and 260,000 deaths in the United States. Extrapolation from the numbers from medical records-based surveys in Sweden suggests approximately 4 million illnesses and 678,000 deaths for Europe. Hospital mortality from severe sepsis is conspicuously high in Germany at 42% compared to Australia (18%), England (32%) and the USA (23%).
In 2017 there were around 49 million sepsis cases worldwide, of which around 11 million were fatal. More than 20 million people were affected by infants and children up to the age of 5 and around 5 million children and adolescents between the ages of 5 and 19. 3 million or 450,000 died of sepsis. Estimates so far have been based primarily on billing data from hospitalized adults in seven high-income countries and assume 19.4 million sepsis cases and 5.3 million sepsis-related deaths annually. In 2015, infectious diseases and sepsis in newborns and children under 5 years of age caused more than 50% of all deaths in Southeast Asia and sub-Saharan Africa.
In the WHO Sepsis Resolution “Improving the Prevention, Diagnosis and Clinical Management of Sepsis” and the accompanying report it is made clear that sepsis is the common, often fatal end-line of most infectious diseases and bacteria, viruses, fungi and parasites (e.g. malaria pathogens) can cause sepsis. It is also made clear that
- Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , Escherichia coli , Salmonella spp. and Neisseria meningitidis are the most common bacterial pathogens,
- Sepsis or septic shock often by seasonal influenza / flu virus , dengue virus and other highly infectious notifiable pathogens such as avian and swine flu viruses , coronaviruses , and more recently Ebola and viruses yellow fever are caused and
- Sepsis often develops outside of the hospital setting as the worsening of common and preventable infections of the respiratory tract, urinary tract, abdomen, skin, and wounds. Infections of the brain, heart valves and infected implants such as vascular and joint prostheses as well as vascular catheters and indwelling venous catheters can also be the starting point for sepsis.
According to the definition updated in 2016:
"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection."
"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection."
Until 1992, the sepsis definition according to Hugo Schottmüller from 1914 was valid in Germany , for which detection of an infectious agent in the blood culture was a prerequisite for the diagnosis of sepsis:
"Sepsis is present when a focus has formed within the body from which pathogenic bacteria continuously or periodically enter the circulation in such a way that this invasion triggers subjective and objective symptoms."
In 1992, as part of a US consensus conference, sepsis was defined based on the detection or suspicion of an infection and the presence of at least two of four criteria for a so-called systemic inflammation reaction (SIRS) . The SIRS criteria are fever or low temperature, increased heart rate, increased respiratory rate and an increased or decreased number of leukocytes in the blood count. A distinction was made between sepsis without organ dysfunction, severe sepsis (i.e. sepsis with at least one organ dysfunction) and septic shock. These definitions, which were again insignificantly changed in 2009, were modified in a third consensus conference in 2016 so that the prerequisite for the definition of sepsis is no longer the existence of at least 2 of the 4 SIRS criteria. The prerequisite for sepsis is the presence of at least one organ dysfunction, the term severe sepsis has been abandoned and the term septic shock has been retained. Consequently, the terms bloodstream infection and septicemia have also been abandoned. This definition was also referred to in the WHO sepsis resolution “Improving the prevention, diagnosis and clinical management of sepsis”.
"Sepsis is the totality of life-threatening clinical symptoms and pathophysiological changes as a reaction to the action of pathogenic germs and their products that penetrate the bloodstream from a focus of infection, activate the large biological cascade systems and special cell systems and trigger the formation and release of humoral and cellular mediators . "
The pathophysiological reactions in sepsis are essentially determined by the type and virulence of the pathogen causing the infection and the immune status or the defense reactions of the body (host response) to the invading pathogen. In people with normal immune competence, the early phase is usually characterized by signs of hyperinflammation , which lead to the term systemic inflammation reaction. abbreviated SIRS - led. However, it very quickly became clear that this reaction in immunocompetent patients is accompanied by an immunomodulatory counterreaction in the early phase and has been referred to as " Compensatory Anti-inflammatory Response Syndrome " (CARS). In the first 24 hours after the onset of sepsis, hyperinflammation predominates, while in the following days an immune status characterized by immunosuppression can set in. The host response not only stimulates all factors of the innate and adaptive immune system, but also leads to a complex interaction between the immune system and the coagulation system , which leads to a stimulation of procoagulant and anticoagulant factors of the coagulation system and through the signs consumption coagulopathy with disseminated intravascular coagulation and endothelial dysfunction.
These reactions, also known as the sepsis cascade, within the framework of the host response are triggered by a series of microbial factors that are summarized as pathogen-associated molecular patterns (PAMPs). These include lipopolysaccharides and flagellin in Gram-negative bacteria and muramyl dipeptides from the cell wall of Gram-positive bacteria and also bacterial DNA . These PAMPs are recognized by the so-called pattern recognition receptors (PRRs) of the innate immune system. As a result, transcription factors such as nuclear factor-kappa B and activator protein-1 are stimulated , which lead to an increased upregulation of pro- and anti-inflammatory cytokines , the so-called cytokine storm .
This host response leads to the multiple organ failure characteristic of sepsis through the following mechanisms: The endothelial dysfunction contributes to the escape of fluid into the alveoli of the lungs via an increased permeability of the pulmonary capillary vessels and leads to pulmonary edema or Acute Respiratory Distress Syndrome (ARDS). The impairment of the liver's cellular utilization of oxygen and the impairment of the transporter systems for the excretion of bile salts lead to acute liver failure and the associated yellowing of the skin. The disturbances in the oxygen supply to the tubular cells of the kidneys lead to acute kidney failure . The vasodilation of the venous and arterial vessels and the intravascular fluid loss due to the increased permeability of the microcirculation lead to a decrease in the pumping capacity of the heart and a drop in blood pressure. The negative inotropic effects of some cytokines, the disturbance of calcium transport with impairment of the production of adenosine triphosphate (ATP) lead to the weakening of the function of the heart muscle and can cause heart failure. In the gastrointestinal tract, the increased permeability of the intestinal mucosa can lead to changes in the intestinal flora and mucosal bleeding as well as paralytic ileus . In the central nervous system, there is direct damage to the brain cells and disorders of the neurotransmitters that trigger the mental changes.
As part of the new definition of sepsis, the proposal to quantify sepsis-related organ dysfunction was also made. For this purpose, the so-called Sequential [Sepsis-related] Organ Failure Assessment Score - SOFA for short - is suggested for use in the intensive care unit or for clinical sepsis research . For each organ system, up to 4 points can be awarded for the functional restriction of the following organ systems:
- Respiration ( Horovitz quotient , PaO2 / FiO2)
- Clotting ( platelet count )
- Liver ( bilirubin level )
- Cardiovascular system ( blood pressure or catecholamine requirement )
- Brain ( Glasgow Coma Scale )
- Kidney ( creatinine level or amount of urine)
Sepsis is diagnosed when there is an acute increase of two or more points on the above scale with a confirmed or suspected infection. In addition, a simplified quick SOFA score ( qSOFA ) with only three clinical signs of organ dysfunction was proposed, which is intended to help identify patients outside of intensive care units. The criteria for the qSOFA are:
- Acute changes in consciousness
- Respiratory rate ≥ 22 / min
- systolic blood pressure ≤ 100 mmHg.
For a suspected diagnosis of sepsis, according to the new definition of sepsis, in the case of confirmed or suspected infection, the presence of one of the 3 symptoms is sufficient as a clear warning for sepsis. If two or all three of these symptoms exist, the patient is at particularly high risk and immediate medical treatment is urgently required.
The evaluation of this score showed that the score is superior to the so-called SIRS criteria for prognosis, but is too unspecific for early identification. The SIRS criteria and / or the so-called National Early Warning Score (NEWS) , as used in the United Kingdom and other Anglo-Saxon countries, are more suitable for the early detection of a severe infection or early sepsis .
There is no single specific key symptom for sepsis, therefore the suspicion of sepsis has to be made on the basis of a combination of individual clinical symptoms, which can vary in severity and frequency.
|in adults (at least 2 of the following symptoms)||in children (at least 2 of the following symptoms)||in infants / young children under 5 years of age|
|Fever, chills||Rapid heavy breathing||Do not drink / eat|
|Acute change in personality / confusion||High fever, convulsions, or an epileptic fit||Repeated vomiting|
|Shortness of breath, rapid breathing||Blotchy, bluish, or very pale skin||Has not passed urine for 12 hours|
|Rapid pulse, drop in blood pressure||Has a rash that cannot be “pushed away” with your finger|
|Never known severe feeling of illness||Sleepy or very difficult to wake up|
|Blotchy skin or bluish discoloration of the skin||Feels unnaturally cold|
|Hardly any urine output for a whole day|
Few people know that sepsis is a life-threatening emergency like heart attack and stroke that requires immediate treatment.
The suspected diagnosis of sepsis must be confirmed by a medical, clinical examination of the patient and an attempt must be made to identify the source of the infection with the support of imaging procedures such as ultrasound, X-rays, computed tomography (CT) or magnetic resonance imaging (MRT). In addition, it is of great importance to use microbiological methods to find the causative infectious agent. Other important measures to clarify the presence of an infection are laboratory blood tests to determine inflammation parameters and laboratory parameters that indicate organ dysfunction. Of the more than one hundred proposed biomarkers of sepsis, only a few have been adequately investigated and have so far found their way into everyday clinical practice. These include C-reactive protein , procalcitonin, and the cytokines IL-6 and IL-8 .
Despite advances in molecular diagnostic techniques, the classic incubation of blood culture and materials from other body compartments is still the gold standard for identifying pathogens in sepsis and infections. The main disadvantage of this process is its slowness; pathogen identification usually takes significantly longer than 24 hours. However, a number of methods are in development and clinical evaluation that promise to make pathogen diagnostics, which is an important prerequisite for effective sepsis therapy, faster and more sensitive and, moreover, to accelerate the testing of the pathogen's sensitivity to microbial substances.
Of the sepsis markers currently used in the clinic, procalcitonin has been evaluated most comprehensively. It has been shown that it helps to reduce the use of antibiotics and that this can be accompanied by an improvement in the chances of survival.
Timely diagnosis and therapy increase the chances of survival. Current international and national treatment guidelines recommend a number of core measures that should be carried out as quickly as possible or within an hour of the diagnosis. The most important elements of this bundling strategy are:
- Blood sampling for blood cultures prior to the administration of antibiotics and for the determination of lactate in the blood
- Calculated therapy with a broad spectrum antibiotic
- Intravenous administration of crystalloid fluid if there are signs of a lack of volume or insufficient blood supply to the tissues
- Give oxygen if there are signs of a lack of oxygen
In addition to antibiotic and fluid therapy, the treatment of sepsis - if indicated - includes drainage of abscesses and infected fluid accumulations, the removal of infected catheters and implants and surgical focal treatment such as B. the removal of an inflamed gallbladder or the appendix and a support or replacement of failed organ systems. These include kidney replacement procedures for kidney failure, artificial respiration for lung failure and, if necessary, the administration of blood or blood products and adequate nutrition - preferably via a gastric tube and, if necessary, intravenously.
In the case of severe septic shock, based on current studies and meta-analyzes, accompanying therapy with hydrocortisone is also recommended, as this reduces the need for catecholamines to stabilize the circulation and can help reduce the duration of ventilation and stay in the intensive care unit. There is no scientifically reliable evidence for the effectiveness of a large number of other so-called adjunctive, immunomodulatory therapy methods. This also applies to processes for the elimination of endotoxin or cytokines by endotoxin filters, hemoadsorption processes with cytokine adsorption filters and early hemodialysis. Older procedures such as Early Goal-Directed Therapy are obsolete.
HAT therapy has recently been recommended ( hydrocortisone , ascorbic acid , thiamine ), as clinical studies have shown the synergistic effectiveness. Randomized studies to prove its effectiveness are currently ongoing.
Secondary diseases and long-term consequences
After discharge from the hospital, about half of the patients with sepsis do not suffer any serious consequences. Around a third dies in the following year and around a sixth sustains severe, long-lasting damage to health (e.g. functional, cognitive and psychological impairments such as anxiety disorders, depression or post-traumatic stress disorders). About 40% of patients are re-admitted within 90 days of discharge. In addition, the risk of re-infection, acute kidney failure and cardiovascular events is increased in sepsis survivors.
Post-sepsis complications pose a major challenge to national health systems. In addition, the everyday skills and quality of life of those affected can be significantly restricted by the consequences of sepsis. Due to the lack of knowledge about the consequences of sepsis, there is also a lack of concrete, sepsis-specific rehabilitation offers. If sepsis survivors are treated in rehab facilities, this is usually done in facilities that specialize in the treatment of special organ systems and the consequences of diseases such as: B. specialize in heart attack, stroke or severe trauma.
Sepsis is one of the most common and cost-intensive diseases in the inpatient sector. Cost factors are the frequent re-admissions and the long-lasting consequences of illness such as long-term ventilation and dialysis, but also long-term inability to work and early retirement. With an annual cost of $ 24 billion, sepsis ranks number one in hospital care costs in the United States. In Germany, the direct treatment costs for sepsis in the outpatient and inpatient sector were estimated at 7.5 billion euros in 2013. The cost of the long-term consequences of sepsis is likely to be significantly higher. However, no calculations are currently available for Germany.
Importance of prevention and risk factors
In the sepsis resolution, the WHO assumes that the majority of sepsis-related deaths are preventable. The essential elements here are the avoidance of infections through vaccination and strict observance of the hygiene rules in hospitals and all treatment and care facilities in the health sector and in home care. In more resource-limited countries, this requires access to clean water and the existence of minimum sanitary standards. It applies to all regions of the world that early sepsis detection and treatment as well as access to suitable treatment facilities can significantly reduce sepsis mortality.
In Germany there is little knowledge about the prevention and early detection of sepsis. A representative survey of people over 60 years of age in 2017 showed that 88% were familiar with the term sepsis, but the causes and symptoms of the disease are largely unknown. Only 17% of German citizens know that sepsis is triggered by infections against which one can protect oneself against, for example, vaccinations against pneumococci and influenza. This partly explains the significantly lower vaccination rate against pneumococci in Germany (31.4%) compared to the USA (63.6%), England (69.8%) and Australia (56.0%). The vaccination rate against influenza is also lower in Germany at 31.4% than in the USA (69.1%), England (71.1%) and Australia (74.6%). The Standing Vaccination Commission (STIKO) at the RKI has specific vaccination recommendations, especially for risk groups of sepsis, to which about 34.5 million German citizens can be assigned .
Risk factors for sepsis include old age, chronic diseases of the lungs, heart, liver, kidneys, diabetes mellitus , alcoholism , treatment with immunosuppressive drugs, and splenic disease . Cancer and HIV patients also have a significantly increased risk of infection and sepsis.
The occurrence and course of the disease are determined by the patient's defenses and the aggressiveness (virulence) of the causative pathogen. Chronic diseases - such as chronic obstructive pulmonary disease, cancer, liver cirrhosis, AIDS and other diseases of the immune system - bring with them an increased risk of sepsis. Demographic and social factors - such as (male) gender, diet, lifestyle (for example tobacco and alcohol consumption) and poverty - also increase susceptibility to infections and sepsis.
The WHO Sepsis Resolution
In 2017 the World Health Organization (WHO) passed the resolution "Improving the prevention, diagnosis and clinical management of sepsis". The reasons for this were the enormous sepsis-related disease burden and the knowledge that the majority of deaths can be avoided. At the global level, WHO has given this resolution a high priority. It urges its 194 member states to integrate these demands into their national health strategies.
Requirements of the WHO Sepsis Resolution:
- Improving early detection through the use of the word sepsis, increasing awareness and providing information about the early symptoms of sepsis in all medical and social areas
- Increase in vaccination rates for groups at risk against seasonal flu (influenza), pneumococci and other infections that can lead to sepsis
- Avoidance of nosocomial infections in hospitals, care facilities and outpatient settings by improving preventive measures
- Optimization of antibiotic therapy through targeted, timely use
- Reducing antibiotic resistance by avoiding improper prescriptions
- Development of effective strategies for dealing with patients infected with multi-resistant germs and effective management of outbreaks of multi-resistant germs
- Further develop effective prevention and containment strategies for pandemics and epidemics
- Use and improvement of the ICD classification system to track the development of sepsis incidence and mortality and antibiotic resistance
- Promotion of sepsis research and development of innovative, effective diagnostics and therapeutics
- Creation of suitable care structures for sepsis survivors
World Sepsis Day / World Sepsis Day
World Sepsis Day has been taking place on September 13th every year since 2012 to draw attention to the disease and its serious consequences. Numerous international campaigns and a web-based World Sepsis Congress on the subject of sepsis take place every two years. World Sepsis Day is coordinated by the Global Sepsis Alliance.
Global Sepsis Alliance
The Global Sepsis Alliance (GSA) brings together the members of the global sepsis community, in which over 100 organizations for affected people and medical societies from numerous specialist areas have come together to fight sepsis. It was the driving force behind the WHO Sepsis Resolution.
Under the umbrella of the GSA, the African Sepsis Alliance (ASA) and the European Sepsis Alliance (ESA) were founded, each made up of the members of the region / continent.
Since 15,000–20,000 patients are considered avoidable annually in Germany, a broad alliance of over 30 medical societies, professional associations, specialist experts and patient organizations is calling for a national sepsis plan under the direction of the Sepsis Foundation and under the auspices of the Patient Safety Action Group (APS) . In June 2018, the Joint Conference of Health Ministers (GMK) asked the Federal Ministry of Health (BMG) to set up an expert commission at the Robert Koch Institute to discuss the implementation of the requirements of the WHO resolution. However, no concrete steps have yet been taken.
Since the sepsis mortality rate in Germany is high compared to other high-income countries and there is scientific evidence of the effectiveness of quality improvement measures at the state and hospital level, in 2017 the patient representatives in the Federal Joint Committee (G-BA) submitted an application for introduced better quality assurance to the G-BA. In the meantime, the Institute for Quality Assurance and Transparency in Health Care (IQTIG) has been commissioned by the G-BA to develop measures to develop a quality assurance procedure for the treatment of sepsis.
Patient organizations, specialist societies and research associations
In Germany, people who are or were affected by sepsis came together for the first time in 2005, from which the Deutsche Sepsis-Hilfe e. V. formed. In 2012, the Sepsis Foundation was founded as a non-profit organization in Jena with the goal of "sustainably reducing deaths from sepsis". To this end, she is committed to research and science as well as to education and prevention. The founding members of the Sepsis Foundation were the German Sepsis Society and the Jena University Hospital. The former competence network for clinical sepsis research "SepNet" works as an independent study group under the umbrella of the Sepsis Foundation. The sepsis aid e. V. is represented on the Board of Trustees of the Sepsis Foundation. The German Sepsis Society (DSG) is a medical society that has set itself the goal of "building and sharpening the understanding of the clinical picture of sepsis both in the public and in the medical community". The DSG was founded in 2001 and holds the Weimar Sepsis Update Congress every two years. The Sepsis Help e. V., the Sepsis Foundation and the German Sepsis Society are member organizations of the Global Sepsis Alliance.
Although sepsis is a relevant problem for many specialist groups, sepsis is not seen as a priority by any medical discipline.
Research associations and specialist societies
- Center for Sepsis Control and Care (CSCC)
- Central German Sepsis Cohort (MSC)
- German Quality Alliance Sepsis (DQS)
- German Sepsis Society (DSG)
- European Society for Intensive Care Medicine (ESICM)
- International Sepsis Forum (ISF)
- Research area “Infections and Sepsis” in the genome research network
- Austrian Sepsis Society / Sepsis Network Austria
Other organizations and associations at international level
- National Health Service , which, in close cooperation with organizations for those affected, informs laypeople and schoolchildren about prevention options and early symptoms of sepsis
- Centers for Disease Control and Prevention (CDC)
- UK Sepsis Trust
- Sepsis Alliance
- Rory Staunton Foundation
In Austria, " invasive bacterial diseases ( meningitis and sepsis)" [z. B. by meningococci , pneumococci , Haemophilus influenzae ] according to paragraph 1 number 2 Epidemic Act 1950 in case of illness and death notifiable . Doctors and laboratories, among others, are obliged to report this ( Epidemics Act).
Sepsis should also be considered when investigating the following diseases (or syndromes):
- Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , pp. 36-40.
- Deutsche Sepsis-Hilfe - The international first and to date only contact point for sepsis sufferers, relatives and survivors. The non-profit association provides layperson-friendly information on all questions regarding / after sepsis. An information telephone has also been set up for those seeking help.
- German Sepsis Society - The medical society aims at a better understanding in the public and in medicine. She published u. a. the guidelines on sepsis , organizes further training courses as well as the International Sepsis Congress in Weimar and provides information about the symptoms of sepsis.
- SepNet Study Group - The study group can be seen as a continuation of the Sepsis Competence Network (SepNet). She conducts medical studies to diagnose and treat sepsis.
- Center for Sepsis Control and Care (CSCC) The integrated research and treatment center for sepsis, which is funded by the Federal Ministry of Education and Research (BMBF).
- Sepsis Foundation
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