Sepsis

In addition to symptoms related to the actual cause, people with sepsis may have a fever, low body temperature, rapid breathing, a fast heart rate, confusion, and edema. Diastolic blood pressure falls during the early stages of sepsis, causing a widening/increasing of pulse pressure, which is the difference between the systolic and diastolic blood pressures. If sepsis becomes severe and hemodynamic compromise advances, the systolic pressure also decreases, causing a narrowing/decreasing of pulse pressure. A pulse pressure of over 70 mmHg in patients with sepsis is correlated with an increased chance of survival. == Cause ==

of a German hospital (2015) with severe sepsis caused by a chain reaction of incidental negative events after a prior surgery of the abdomen. After an emergency surgery, he received antibiotics, parenteral nutrition, and pain killers via automated injection employing infusion pumps (background right). Hemodialysis via the machine on the left became necessary due to kidney malfunction and multiple organ dysfunction syndrome. After three months in the hospital, the patient recovered within a month and has since then fully recovered (as of 2023). Infections leading to sepsis are usually bacterial but may be fungal, parasitic, or viral. Gram-positive bacteria were the primary cause of sepsis before the introduction of antibiotics in the 1950s. After the introduction of antibiotics, gram-negative bacteria became the predominant cause of sepsis from the 1960s to the 1980s. After the 1980s, gram-positive bacteria, most commonly staphylococci, are thought to cause more than 50% of cases of sepsis. Other commonly implicated bacteria include Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella species. Fungal sepsis accounts for approximately 5% of severe sepsis and septic shock cases; the most common cause of fungal sepsis is an infection by Candida species of yeast, a frequent hospital-acquired infection. The most common causes for parasitic sepsis are Plasmodium (which leads to malaria), Schistosoma and Echinococcus. The most common sites of infection resulting in severe sepsis are the lungs, the abdomen, and the urinary tract. 40–60% of infections causing sepsis originate in the lungs, 15–30% are abdominal infections, and 15–30% are bladder, kidney, skin, or soft tissue infections. But the site of infection, as well as the causative infectious pathogen, varies depending on geographic location and region. == Pathophysiology ==

Sepsis is caused by a combination of factors related to the particular invading pathogen(s) and the status of the immune system of the host. Systemic inflammation, endothelial injury, and dysregulated coagulation activate platelets in the early phases of the condition. Host factors Upon detection of microbial antigens, the host systemic immune system is activated. Immune cells not only recognise pathogen-associated molecular patterns but also damage-associated molecular patterns from damaged tissues. An uncontrolled immune response is then activated because leukocytes are not recruited to the specific site of infection, but instead, they are recruited all over the body. Then, an immunosuppression state ensues when the proinflammatory T helper cell 1 (TH1) is shifted to TH2, mediated by interleukin 10, which is known as "compensatory anti-inflammatory response syndrome". The apoptosis (cell death) of lymphocytes further worsens the immunosuppression. Neutrophils, monocytes, macrophages, dendritic cells, CD4+ T cells, and B cells all undergo apoptosis, whereas regulatory T cells are more apoptosis-resistant. Subsequently, multiple organ failure ensues because tissues are unable to use oxygen efficiently due to inhibition of cytochrome c oxidase, possibly as part of a "cell hibernation" mechanism, to conserve oxygen. Inflammatory responses cause multiple organ dysfunction syndrome through various mechanisms as described below. Increased permeability of the lung vessels causes leaking of fluids into alveoli, which results in pulmonary edema and acute respiratory distress syndrome (ARDS). Impaired utilization of oxygen in the liver impairs bile salt transport, causing jaundice (yellowish discoloration of the skin). In the kidneys, inadequate oxygenation results in tubular epithelial cell injury (of the cells lining the kidney tubules), and thus causes acute kidney injury (AKI). Meanwhile, in the heart, impaired calcium transport and low production of adenosine triphosphate (ATP) can cause myocardial depression, reducing cardiac contractility and causing heart failure. In the gastrointestinal tract, increased permeability of the mucosa alters the microflora, causing mucosal bleeding and paralytic ileus. In the central nervous system, direct damage of the brain cells and disturbances of neurotransmissions causes altered mental status. Cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6 may activate procoagulation factors in the cells lining blood vessels, leading to endothelial damage. The damaged endothelial surface inhibits anticoagulant properties as well as increases antifibrinolysis, which may lead to intravascular clotting, the formation of blood clots in small blood vessels, and multiple organ failure. The low blood pressure seen in those with sepsis is the result of various processes, including: • Excessive production of chemicals that dilate blood vessels such as nitric oxide. • A deficiency of chemicals that constrict blood vessels such as vasopressin. • Activation of ATP-sensitive potassium channels. In those with severe sepsis and septic shock, this sequence of events leads to a type of circulatory shock known as distributive shock. == Diagnosis ==

Early diagnosis is necessary to properly manage sepsis, as the initiation of rapid therapy is key to reducing deaths from severe sepsis. Within the first three hours of suspected sepsis, diagnostic studies should include white blood cell counts, measuring serum lactate, and obtaining appropriate cultures before starting antibiotics, so long as this does not delay their use by more than 45 minutes. Some advantages of the qSOFA score are that it can be administered quickly and does not require labs. A 2013 review concluded moderate-quality evidence exists to support the use of the procalcitonin level as a method to distinguish sepsis from non-infectious causes of SIRS. A 2012 systematic review found that soluble urokinase-type plasminogen activator receptor (SuPAR) is a nonspecific marker of inflammation and does not accurately diagnose sepsis. == Treatment ==

Sepsis requires immediate treatment in a hospital as it can quickly worsen. Current professional recommendations include several actions ("bundles") to be followed as soon as possible after diagnosis. Within the first three hours, someone with sepsis should have received antibiotics and intravenous fluids if there is evidence of either low blood pressure or other evidence for inadequate blood supply to organs (as evidenced by a raised level of lactate); blood cultures should also be obtained within this period. After six hours, the blood pressure should be adequate, close monitoring of blood pressure and blood supply to organs should be in place, and the lactate should be measured again if initially it was raised. Norepinephrine is often used as a first-line treatment for hypotensive septic shock because evidence shows that there is a relative deficiency of vasopressin when shock continues for 24 to 48 hours. Early goal-directed therapy Early goal directed therapy (EGDT) is an approach to the management of severe sepsis during the initial 6 hours after diagnosis. Reviews mention that an intake of 3.0 g/day, which requires intravenous administration, may be needed to maintain normal plasma concentrations in people with sepsis or severe burn injury. == Prognosis ==

Sepsis proves fatal for approximately 24.4% of people, and septic shock proves fatal for 34.7% of people within 30 days (with fatality rates for sepsis and septic shock being 32.2% and 38.5% after 90 days, respectively). == Epidemiology ==

Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized. The number of new cases of sepsis worldwide is estimated to be 18 million cases per year. In the United States, sepsis affects approximately 3 in 1,000 people, and severe sepsis contributes to more than 200,000 deaths per year. Sepsis occurs in 1–2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization. As it is rarely reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are probably underestimated. A study of U.S. states found approximately 651 hospital stays per 100,000 population with a sepsis diagnosis in 2010. It is the second-leading cause of death in non-coronary intensive care unit (ICU) and the tenth-most-common cause of death overall (the first being heart disease). Children under 12 months of age and elderly people have the highest incidence of severe sepsis. Among people from the U.S. who had multiple sepsis hospital admissions in 2010, those who were discharged to a skilled nursing facility or long-term care following the initial hospitalization were more likely to be readmitted than those discharged to another form of care. A study of 18 U.S. states found that amongst people with Medicare in 2011, sepsis was the second most common principal reason for readmission within 30 days. Several medical conditions increase a person's susceptibility to infection and the development of sepsis. Common sepsis risk factors include age (especially the very young and old); conditions that weaken the immune system such as cancer, diabetes, or the absence of a spleen; and major trauma and burns. From 1979 to 2000, data from the United States National Hospital Discharge Survey showed that the incidence of sepsis increased fourfold, to 240 cases per 100,000 population, with a higher incidence in men when compared to women. However, the global prevalence of sepsis has been estimated to be higher in women. During the same time frame, the in-hospital case fatality rate was reduced from 28% to 18%. However, according to the nationwide inpatient sample from the United States, the incidence of severe sepsis increased from 200 per 10,000 population in 2003 to 300 cases in 2007 for a population aged more than 18 years. The incidence rate is particularly high among infants, with an incidence of 500 cases per 100,000 population. Mortality related to sepsis increases with age, from less than 10% in the age group of 3 to 5 years to 60% by the sixth decade of life. The increase in the average age of the population, alongside the presence of more people with chronic diseases or on immunosuppressive medications, and also the increase in the number of invasive procedures being performed, has led to an increased rate of sepsis. == History ==

" The term "σήψις" (sepsis) was introduced by Hippocrates in the fourth century BC, and it meant the process of decay or decomposition of organic matter. The current terms are dependent on the microorganism that is present: bacteremia if bacteria are present in the blood at abnormal levels and are the causative issue, viremia for viruses, and fungemia for a fungus. and more careful design of preclinical studies. One approach is to rely more on studying biopsies and clinical data from people who have had sepsis, to try to identify biomarkers and drug targets for intervention. == Society and culture ==

Economics Sepsis was the most expensive condition treated in United States' hospital stays in 2013, at an aggregate cost of $23.6 billion for nearly 1.3 million hospitalizations. and again in 2021. Awareness Sepsis Alliance is a charitable organization based in the United States that was created to raise sepsis awareness among both the general public and healthcare professionals. ==Research==

Some authors suggest that initiating sepsis by the normally mutualistic (or neutral) members of the microbiome may not always be an accidental side effect of the deteriorating host immune system. Rather, it is often an adaptive microbial response to a sudden decline of host survival chances. Under this scenario, the microbe species provoking sepsis benefit from monopolizing the future cadaver, utilizing its biomass as decomposers, and then transmitting through soil or water to establish mutualistic relations with new individuals. The bacteria Streptococcus pneumoniae, Escherichia coli, Proteus spp., Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella spp., Clostridium spp., Lactobacillus spp., Bacteroides spp. and the fungi Candida spp. are all capable of such a high level of phenotypic plasticity. Not all cases of sepsis arise through such adaptive microbial strategy switches. A systematic review of trials in 2021 found that the claimed benefits of the protocol could not be confirmed. Overall, the evidence for any role of vitamin C in the treatment of sepsis remains unclear . == See also ==