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Septic shock occurs when a body’s response to an infection (sepsis) leads to life-threatening low blood pressure.
- Compare and contrast the symptoms of: sepsis, severe sepsis, septic shock
- Sepsis results from certain bacterial infections, often acquired in a hospital. Having certain conditions, such as a weakened immune system, certain chronic disorders, an artificial joint, or heart valve increases the risk.
- Symptoms of sepsis include either fever or low body temperature, rapid breathing, chills and shaking, rapid heartbeat, decreased urine output, and confusion or delirium.
- Severe sepsis often causes extremely low blood pressure, which limits blood flow to the body and can result in organ failure and death. This is known as septic shock.
- Sepsis is treated with antibiotics, fluids, and medicines to support blood pressure and prevent organ damage.
- septic shock: A life-threatening condition caused by infection and sepsis, often after surgery or trauma.
- sepsis: A life-threatening medical condition caused by a severe inflammatory response of the human body triggered by the presence of an infectious agent.
- mortality rate: the number of deaths per given unit of population over a given period of time
Sepsis is a potentially deadly medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) that is triggered by an infection. Septic shock is a medical condition as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. Its most common victims are children, immuno-compromised individuals, and the elderly, as their immune systems cannot deal with the infection as effectively as those of healthy adults. Frequently, patients suffering from septic shock are cared for in intensive care units. The mortality rate from septic shock is approximately 25–50%.
Sepsis is an illness in which the body has a severe response to bacteria or other germs. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues. A popular term for sepsis is blood poisoning. Severe sepsis is the systemic inflammatory response, infection, and the presence of organ dysfunction.
A bacterial infection anywhere in the body may set off the response that leads to sepsis. Common places where an infection might start include:
- the bloodstream
- bones (common in children)
- the bowel (usually seen with peritonitis)
- the kidneys (upper urinary tract infection or pyelonephritis )
- the lining of the brain ( meningitis )
- the liver or gallbladder
- the lungs (bacterial pneumonia )
- the skin (cellulitis)
For patients in the hospital, common sites of infection include intravenous lines, surgical wounds, surgical drains, and sites of skin breakdown known as bedsores (decubitus ulcers).
The therapy of sepsis rests on intravenous fluids, antibiotics, surgical drainage of infected fluid collections, and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in pulmonary dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition—preferably by enteral feeding, but if necessary by parenteral nutrition—is important during prolonged illness.
In sepsis, blood pressure drops, resulting in septic shock. Major organs and body systems, including the kidneys, liver, lungs, and central nervous system, stop working properly because of poor blood flow.
Most cases of septic shock are caused by Gram-positive bacteria, followed by endotoxin-producing Gram-negative bacteria. Endotoxins are bacterial membrane lipopolysaccharides (LPS) consisting of a toxic fatty acid (lipid A) core common to all Gram-negative bacteria, and a complex polysaccharide coat (including O antigen) unique for each species. Analogous molecules in the walls of Gram-positive bacteria and fungi can also elicit septic shock. In Gram-negative sepsis, free LPS attaches to a circulating LPS-binding protein, and the complex then binds to a specific receptor (CD14) on monocytes, macrophages, and neutrophils.
If sepsis worsens to the point of end-organ dysfunction (renal failure, liver dysfunction, altered mental status, or heart damage) then the condition is called severe sepsis. Once severe sepsis worsens to the point where blood pressure can no longer be maintained with intravenous fluids alone, then the criteria have been met for septic shock. The precipitating infections which may lead to septic shock if severe enough include appendicitis, pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis, and necrotizing fasciitis.
Treatment primarily consists of the following:
- Volume resuscitation
- Early antibiotic administration
- Early goal directed thearpy
- Rapid source identification and control.
- Support of major organ dysfunction.
There are new drugs that act against the extreme inflammatory response seen in septic shock. These may help limit organ damage.
The mortality rate from sepsis is approximately 40% in adults, and 25% in children, and is significantly greater when left untreated for more than seven days.
What is sepsis?
Sepsis is the body&rsquos extreme response to an infection. It is a life-threatening medical emergency. Sepsis happens when an infection you already have triggers a chain reaction throughout your body. Without timely treatment, sepsis can rapidly lead to tissue damage, organ failure, and death.
Almost any type of infection can lead to sepsis. Infections that lead to sepsis most often start in the lung, urinary tract, skin, or gastrointestinal tract.
You can&rsquot spread sepsis to other people. However, an infection can lead to sepsis, and you can spread some infections to other people. Bacterial infections cause most cases of sepsis. Sepsis can also be a result of other infections, including viral infections, such as COVID-19 or influenza.
What causes sepsis?
When germs get into a person&rsquos body, they can cause an infection. If you don&rsquot stop that infection, it can cause sepsis.
Who is at risk?
Anyone can get an infection, and almost any infection can lead to sepsis. Some people are at higher risk:
People with chronic medical conditions, such as diabetes, lung disease, cancer, and kidney disease
Group A Streptococcus
Group A Streptococcus, also called group A strep, is a bacterium that can cause many different infections. These may cause sepsis. Sometimes incorrectly called blood poisoning, sepsis is the body’s often deadly response to infection. Sepsis kills and disables millions and requires early suspicion and treatment for survival.
Sepsis and septic shock can result from an infection anywhere in the body, such as pneumonia, influenza, or urinary tract infections. Worldwide, one-third of people who develop sepsis die. Many who do survive are left with life-changing effects, such as post-traumatic stress disorder (PTSD), chronic pain and fatigue, organ dysfunction (organs don’t work properly), and/or amputations.
Infections caused by group A strep
Group A bacteria cause several types of infections, most commonly:
How group A strep is spread
Group A strep bacteria live in your nose and throat, so they are spread through droplets that become airborne from coughing or sneezing or by direct contact with the mucus. You might breathe droplets in if you’re close enough when an infected person coughs or sneezes. As well, the droplets may land on a solid object that you touch later. This type of contact may also occur if people who are infected blow their nose and touch an object before washing their hands. Either way, if the bacteria are transferred to your hand or fingers and you put your hand to your face, you can become infected.
If the skin is infected, as with cellulitis or impetigo, the bacteria must come in contact with a spot of skin that had an open area, such as a cut, scrape, or bite. The opening may be so tiny that you didn’t notice anything beforehand. Impetigo is common among young children as they share toys and play together.
Invasive group A strep disease
While it’s common for group A strep to exist in your throat and nose, and on your skin, it is not common inside your body. When these bacteria enter your body, they can cause infections such as necrotizing fasciitis (often called “flesh eating disease”) and toxic shock syndrome. These are called invasive group A strep infections.
The symptoms of a group A strep infection depend on what part of the body is infected but the common symptoms include pain in the affected area, redness, and swelling. If the infection progresses or is a systemic infection, such as scarlet fever or toxic shock syndrome, you would develop fever, muscle aches, and flu-like symptoms.
Treatment for the infections include appropriate antibiotics. Sepsis caused by group A strep should be treated urgently with both antibiotics and IV fluids. For people with necrotizing fasciitis, surgery may likely be needed to remove the affected tissue.
If you suspect sepsis, call 9-1-1 or go to a hospital and tell your medical professional, “I AM CONCERNED ABOUT SEPSIS.”
Would you like to share your story about sepsis or read about others who have had sepsis? Please visit Faces of Sepsis, where you will find hundreds of stories from survivors and tributes to those who died from sepsis.
The Centers for Disease Control and Prevention also has group A strep information for the public.
DIC and DIT in hemostasis and sepsis
To embrace the genuine characters between “DIC” and DIT, the pathophysiological mechanism of true DIC, “DIC” and DIT occurring as hemostasis should be clearly established. Indeed, through the better understanding of sepsis-associated coagulopathy, this has become possible to construct “two-path unifying theory” of hemostasis derived from the insights of endothelial pathogenesis that leads to microthrombogenesis and TTP-like syndrome. This novel theory, which is simple and easily understandable, was proposed and published  and updated in Fig. 2. This effort has allowed us to use the term disseminated intravascular microthrombosis (DIT) instead of “DIC” and endotheliopathy-associated vascular microthrombotic disease (EA-VMTD/DIT) as a distinct disease entity that is associated with TTP-like syndrome [1,2,3,4, 19, 20]. This new identity of “DIC” could provide a paradigm shift in the management of sepsis by utilizing targeted therapies to improve the outcome. In addition, this thesis along with “two-activation theory of the endothelium” (Fig. 3) identifies the true character of “DIC” [1,2,3,4, 20] as well as the mechanisms of thrombogenesis  and different phenotypes of the thrombotic disorder [3, 4, 20].
Three different paths of thrombogenesis that can occur within normal hemostasis. (Reproduced and updated with permission from Chang JC. Blood Coagul Fibrinoplysis. 2018 29:573–84). Two different thrombotic paths, microthrombotic (ULVWF) and fibrinogenic (TF), are initiated in normal hemostasis, but later the two paths must unify to conclude normal hemostasis with passive role of NETs it stops the bleeding in external bodily injury and produce the thrombosis in intravascular injury. However, in the different level (depth) of intravascular injury, thrombogenesis takes two different paths. If the level of intravascular injury is confined to the endothelium, lone ULVWF path become activated and causes microthrombosis (i.e., VMTD) because TF path is not activated. On the other hand, if the level of intravascular injury extends from the endothelium to SET/EVT, TF path becomes also activated and causes macrothrombosis (e.g., DVT). In one theoretical situation, if only SET/EVT is injured, available TF is supposed to activate TF path, but in reality this injury does not cause thrombosis without breached endothelium. However, in pathologic hemostasis, aberrant TF activation occurs and produces fibrin clots (i.e., true DIC) in APL due to TF expression in intravascular space from leukemic promyelocytes. APL is a consumption coagulopathy due to lone activation of TF path. This logic is based on “two-path unifying theory”. Please see Figure 2, showing 3 different thrombosis disorders via microthrombogenesis, fibrinogenesis, macrothrombogenesis, which are annotated in bold face. Each thrombognesis occurs when ULVWF path, TF path or combined paths are activated depending upon the levels of damage in intravascular injury (endothelium and SET/EVT). The characters of microthrombi, fibrin clots and macrothrombus from different paths are very different and produce distinctly different clinical thrombotic disorders . Abbreviations: APL acute promyelocytic leukemia, DIC disseminated intravascular coagulation, DVT deep vein thrombosis, EVT extravascular tissue, NET neutrophil extracellular traps, SET subendothelial tissue, TF tissue factor, ULVWF unusually large von Willebrand factor multimers, VMTD vascular microthrombotic disease
Endothelial molecular pathogenesis and microthrombogenesis in sepsis. (Based on “two-activation theory of the endothelium”). (Reproduced and modified from Thrombosis Journal 201816:20). Endothelial molecular pathogenesis is succinctly illustrated. Endotheliopathy activates two main pathways. Activation of inflammatory pathway produces cytokines, which main function is the modulation of inflammation, including fever and myalgia. Activation of microthrombotic pathway causes much more deadly septic syndromes via generalized EA-VMTD/DIT. Abbreviations: CNSD central nervous system dysfunction, DIC disseminated intravascular coagulation, DIT disseminated intravascular microthrombosis, EA-VMTD endotheliopathy-associated VMTD, FHF fulminant hepatic failure, MAHA microangiopathic hemolytic anemia, SIRS systemic inflammatory response syndrome, TCIP thrombocytopenia in critically ill patients, TTP thrombotic thrombocytopenic purpura, ULVWF unusually large von Willebrand factor multimers, * cell-mediated immune cells are T lymphocyte, macrophage, monocyte, neutrophil, and dendritic cell
The hemostasis in sepsis-induced endotheliopathy has been poorly understood even though research scientists have known that endothelial injury plays a prominent role in sepsis and many other critical illnesses such as trauma, pregnancy, autoimmune disease, cancer and drug/toxin, leading to poorly defined but serious coagulopathy. The frequently noticed early hematologic manifestation is occurrence of unexplained “thrombocytopenia in critically ill patients” (TCIP), which until recently has been a clinical mystery [1, 2]. Now, it has become evident that thrombocytopenia develops due to contribution of platelets in microthrombogenesis and their consumption. Microthrombogenesis is the process of forming microthrombi composed of platelet-unusually large von Willebrand factor (ULVWF) complexes following platelet activation and endothelial exocytosis of ULVWF as a result of endotheliopathy [1,2,3].
EA-VMTD/DIT in sepsis is a unique hemostatic disorder developing via lone activation of ULVWF path without simultaneous activation of TF path according to “two-path unifying theory of hemostasis” [4, 20]. In this article, the pathophysiological mechanism promoting EA-VMTD/DIT in sepsis will be reviewed the molecular pathogenesis of endotheliopathy and hemostasis will be discussed and the clinical phenotypes of various septic syndromes be analyzed. Finally, we should be able to recognize that EA-VMTD/DIT is the underlying clinical disease associated with sepsis-associated coagulopathy and oftentimes presents with hematologic phenotype of TTP-like syndrome.
Pathophysiology of sepsis
There has been a marked evolution in our understanding of the molecular pathobiology and immunology of sepsis. Previously it was felt that hemodynamic manifestations of sepsis were primarily related to the hyperimmune host response to a particular pathogen. 8 However, a large body of work on the molecular basis of sepsis has revealed a far more nuanced and complex interplay between the infectious agent and host that together produce the heterogeneous manifestations of sepsis.
Innate immunity and inflammatory mediators
The first step in the initiation of the host response to the pathogen is the activation of innate immune cells, constituted primarily by macrophages, monocytes, neutrophils, and natural killer cells. 9 This occurs via the binding of pathogen-associated molecular patterns (PAMPs), such as bacterial endotoxins and fungal β-glucans to specific pattern recognition receptors, on these cells. Another source of such interaction are damage-associated molecular patterns (DAMPs) that may be intracellular material or molecules released from dead or damaged host cells, such as ATP and mitochondrial DNA. These bind to specific receptors on monocytes and macrophages such as toll-like receptors (TLRs), C-type leptin receptors, NOD-like receptors (nucleotide-binding oligomerization domain) and RIG-1 like receptors (retinoic acid inducible gene 1). This results in the activation of intracellular signal transduction pathways that cause the transcription and release of proinflammatory cytokines like TNFα, IL-1, and IL-6. In addition, some of the pattern recognition receptors, such as the NOD-like receptor group, can aggregate into larger protein complexes called inflammasomes that are involved in the production of crucial cytokines, such as IL-1β and IL-18 as well as caspases, which are involved in programmed cell death. Proinflammatory cytokines cause activation and proliferation of leukocytes, activation of the complement system, upregulation of endothelial adhesion molecules and chemokine expression, tissue factor production, and induction of hepatic acute phase reactants. In sepsis, there is an exaggeration of the above immune response resulting in collateral damage and death of host cells and tissues.
Dysregulation of hemostasis
In sepsis, there is an intersection between the inflammatory and hemostatic pathways, with the simultaneous activation of both the inflammatory and the coagulation cascades. The spectrum of this interaction can vary from mild thrombocytopenia to fulminant disseminated intravascular coagulation (DIC). The etiology of the dysregulation of coagulation in sepsis is multifactorial. The hypercoagulability of sepsis is thought to be driven by the release of tissue factor from disrupted endothelial cells (other sources include monocytes and polymorphonuclear cells). 10 In fact, in vitro experimental models of endotoxemia and bacteremia have shown a complete inhibition of inflammation-induced thrombin production with the blockade of tissue factor. 11 Tissue factor then causes the systemic activation of the coagulation cascade resulting in the production of thrombin, activation of platelets, and formation of platelet𠄿ibrin clots. These microthrombi can cause local perfusion defects resulting in tissue hypoxia and organ dysfunction.
In addition to the procoagulant effect described above, there is a depression of the anticoagulant effects of protein C and antithrombin that would normally temper the coagulation cascade. Protein C is converted to its active form (activated protein C) by thrombomodulin which itself is activated by thrombin. Activated protein C then exerts an anticoagulant effect by degradation of factors Va and VIIIa acting in concert with activated protein S. It is also known to have potent anti-inflammatory effects via the inhibition of TNFα, IL-1β, and IL-6 and limiting of neutrophil and monocyte adhesion to endothelium. In patients with severe systemic inflammation, such as in sepsis, there are decreased plasma levels of protein C, downregulation of thrombomodulin, and low levels of protein S thus allowing for the unregulated propagation of the coagulation cascade. 12
In addition to the hypercoagulability described above, a reduction of fibrinolysis is also observed as a result of sepsis. 13 As TNFα and IL-1β levels increase, tissue plasminogen activators are released from vascular endothelial cells. The resultant increase in activation of plasmin is blunted by the sustained increase in plasminogen activator inhibitor type 1 (PAI-1). The net effect is diminished fibrinolysis and fibrin removal, which contributes to the perpetuation of microvascular thrombosis.
Interestingly, the initial proinflammatory state of sepsis is often superseded by a prolonged state of immunosuppression. There is a decrease in the number of T cells (helper and cytotoxic) as a result of apoptosis and a decreased response to inflammatory cytokines. 14 Postmortem studies of ICU patients who died of sepsis demonstrated a global depletion of CD4+ and CD8+ T cells, most notably found in the lymphoid organs such as the spleen. Studies have also demonstrated decreased production of crucial cytokines such as IL-6 and TNF in response to endotoxin. 15,16 In septic patients, neutrophils were found to have expressed fewer chemokine receptors, and there was diminished chemotaxis in response to IL-8. 17
The above findings suggest that the immune system in a septic individual is unable to stage an effective immune response to secondary bacterial, viral, or fungal infections. Based on a study that showed that a low lymphocyte count early in sepsis (day 4 of diagnosis) is predictive of both 28-day and 1-year mortality, it has been postulated that early lymphopenia can serve as a biomarker for immunosuppression in sepsis. 18
Cellular, tissue, and organ dysfunction
The underlying mechanism behind tissue and organ dysfunction in sepsis is the decreased delivery to and utilization of oxygen by cells as a result of hypoperfusion. Hypoperfusion occurs due to the cardiovascular dysfunction that is seen in sepsis. 19 The incidence of septic cardiomyopathy varies from 18% to 60% in various studies. It is thought to be related to circulating cytokines, such as TNFα and IL-1β among others, which can cause depression of cardiac myocytes and an interference with their mitochondrial function. The most important feature of septic cardiomyopathy is that it is acute in onset and reversible. Second, the low left ventricular ejection fraction is accompanied by normal or low left ventricular filling pressures (unlike in cardiogenic shock) with increased left ventricular compliance. 20 Multiple studies have shown both systolic and diastolic dysfunction with decreased stroke volumes and increased end-diastolic and end-systolic volumes in sepsis. 21,22 A definite effect on mortality as a result of myocardial depression, however, has not yet been established. In addition, because of the arterial and venous dilation (induced by inflammatory mediators) and consequent reduced venous return, a state of hypotension and distributive shock is produced by sepsis. There is dilation of all three components of the microvasculature𠅊rterioles, venules, and capillaries. This is exacerbated by the leakage of intravascular fluid into the interstitial space as a result of loss of endothelial barrier function induced by alterations in endothelial cadherin and tight junctions. All the above changes in the body’s hemodynamics in conjunction with microvascular thrombosis (described earlier) can result in hypoperfusion of tissues and organs. Consequently, there is increased anaerobic glycolysis in cells resulting in the production of lactic acid. In addition, the reactive oxygen species (ROS) produced by the inflammatory response cause dysfunction of mitochondria and a drop in ATP levels. These mechanisms cause damage at the cellular level. The broader alterations described below that occur in the tissue and organs collectively and cumulatively contribute to much of the morbidity and mortality of sepsis.
There are significant alterations to the endothelium with disruption of its barrier function, vasodilation, increased leukocyte adhesion, and the creation of a procoagulant state. This results in accumulation of edema fluid in the interstitial spaces, body cavities, and subcutaneous tissue. In the lungs, there is disruption of the alveolar𠄾ndothelial barrier with accumulation of protein-rich fluid in the interstitial lung spaces and alveoli. This can cause a ventilation–perfusion mismatch, hypoxia, and decreased lung compliance producing acute respiratory distress syndrome (ARDS) in extreme cases. In the kidneys, a combination of reduced renal perfusion, acute tubular necrosis, and more subtle defects in the microvasculature and tubules together produce varying degrees of acute kidney injury. In the gastrointestinal tract, the increased permeability of the mucosal lining results both in bacterial translocation across the bowel well and autodigestion of the bowel by luminal enzymes. In the liver, there is a suppression of bilirubin clearance producing cholestasis. Altered mentation is commonly noted in sepsis and is indicative of CNS dysfunction. The endothelial changes described above undermine the blood𠄻rain barrier, causing the entry of toxins, inflammatory cells, and cytokines. The ensuing changes of cerebral edema, neurotransmitter disruption, oxidative stress, and white matter damage give rise to a clinical spectrum of septic encephalopathy that varies from mild confusion to delirium and coma. Sepsis is known to produce a catabolic state. There is a rapid and significant breakdown of muscle to produce amino acids for gluconeogenesis that will fuel the immune cells. In addition, increased insulin resistance can result in a state of hyperglycemia.
Diagnosis, screening and prevention
No single diagnostic test is (and will ever be) available that establishes the diagnosis of sepsis or septic shock. Sepsis and septic shock are clinical syndromes defined by a constellation of signs, symptoms, laboratory abnormalities and characteristic pathophysiological derangements. Clinicians often use these terms in an imprecise manner, which adds to the confusion when describing what is meant by the term sepsis. The 1991 SIRS criteria (Box 1), which include parameters on temperature, heart rate and white blood cell count, have proven to be rather difficult to translate into clinical practice or even use effectively as entry criteria for clinical trials of sepsis. Using the SIRS criteria plus infection as the definition of sepsis could be applied to a large percentage of patients who are admitted with uncomplicated infections for whom the label of ‘sepsis’ seemed out of place or irrelevant. For example, most children with middle ear infections will often have two or three SIRS criteria (fever, tachycardia and leukocytosis) to consider them as ‘septic’ based on the SIRS criteria makes no clinical sense, especially when most are prescribed oral antibiotics for treatment at home. Similarly, in a large number of patients, especially those in whom antibiotics have been started empirically, the detection of bacteria in the blood or bodily fluids is often problematic. In as many as 30% of the cases of presumed sepsis, no pathogen is ever identified. In many cases, evidence of infection is inferred radiologically or from haematological measurements 93 .
The aforementioned proposed 2015 approach to the diagnosis of sepsis and septic shock is based on clinical realities and easily obtainable physiological and laboratory parameters 4 (Box 2). What distinguishes sepsis from an otherwise localized microbial infection is that the host response is dysfunctional, generalized and contributes to multiple organ dysfunction and potentially septic shock 94 . Furthermore, sepsis is characterized by organ dysfunction in tissues that are not directly involved with the infectious process itself. A quick bedside assessment of organ injury has been proposed using readily available clinical measurements 95 . Indeed, early evidence of septic shock is manifested by hypoperfusion of tissues with resultant dysfunction and eventually by organ failure that occurs simultaneously or closely following the inflammatory event 96 .
Defining septic shock
Conceptually, septicaemia refers to sepsis with positive blood cultures, although it is an archaic term that is generally avoided. Blood cultures are not commonly positive, in part because bacteria do not need to circulate in the bloodstream to induce sepsis, and in part because some patients are being treated empirically with antibiotics at the time of testing and before the diagnosis. Thus, the term septicaemia has been abandoned. The term ‘septic shock’ remains current and is defined as a state in which sepsis is associated with cardiovascular dysfunction manifested by persistant hypotension despite an adequate fluid (volume) resuscitation to exclude the possibility of volume depletion as a cause of hypotension. Hypotension is operationally defined as the requirement for vasopressor therapy to maintain a mean arterial pressure of >65 mmHg and a plasma lactate level of >2 mmol per l. An increased level of serum lactate is a hallmark of tissue hypoperfusion and septic shock, and is helpful in early diagnosis. The usual cut-off value for an abnormally high lactate level is ≥2 mmol per l, but Casserly et al. 97 have recommended the use of a lactate level of ≥4 mmol per l for inclusion in sepsis clinical trials.
The ability of biomarkers to identify the presence and severity of sepsis has generally been limited. Many biomarkers based on the magnitude of the inflammatory response, such as IL-6, IL-10, CCL2, CXCL10 and HMGB1, have shown good correlation with the severity of sepsis and clinical outcome in population-based studies, but have proven less useful for individual patients — in large part because of the lack of specificity of the biomarkers and the commonality of the early inflammatory response. Our ability to distinguish sepsis from non-infectious critical illness and to prognosticate outcome is very limited.
The one exception is in the use of procalcitonin to distinguish sepsis from non-infectious critical illness and to guide the use of antibiotic therapy 98 . Procalcitonin is a peptide precursor of the hormone calcitonin that is produced by parafollicular cells of the thyroid and by the neuroendocrine cells of the lung and the intestine. In healthy individuals, procalcitonin levels are nearly undetectable. Initially, there was considerable enthusiasm that procalcitonin concentrations could distinguish sepsis from non-septic critical illness and to predict clinical outcomes better than inflammatory cytokines or clinical criteria. Although controversial, the general consensus to date is that procalcitonin is not an effective diagnostic measurement to rule-in or rule-out sepsis or bacterial infection, or for prognostication, in the absence of additional clinical data 98,99 . However, this notion has been challenged by the findings of a recent multicentre study in >1,500 critically ill patients with presumed bacterial infections and sepsis. In this study, the duration of antibiotic treatment, 28-day mortality and 1-year mortality were significantly lower in the procalcitonin-guided group than in patients who were managed without the procalcitonin measurement 100 . Furthermore, two recent large meta-analyses of data from patients with respiratory infections showed that procalcitonin to guide antibiotic treatment in patients with respiratory infections was not associated with higher mortality rates or treatment failure 101,102 . Antibiotic use was significantly reduced across different clinical settings and diagnoses.
Prevention of sepsis and septic shock is based on good clinical practices to reduce the incidence of infections, particularly in high-risk populations. In the community setting, prevention is centred on vaccination for at-risk populations, such as for pneumococcal pneumonia in the elderly and meningococcal infections in adolescents and young adults. Other high-risk populations include those with advanced-stage cancer, type I diabetes, end-stage renal disease, congestive heart failure and chronic obstructive pulmonary disease (Box 3). Prevention in this group of individuals entails good hygiene, maintaining mobility and reducing frailty, preserving nutritional status and adequately treating local wound infections.
Hospitalized patients pose a much greater challenge to sepsis prevention because of their concordant illness and an environment rich in pathogens. In this case, reducing primary length of stay and minimizing the frequency and duration of invasive procedures that disrupt natural barriers are often some of the most effective tools. Simple hand washing, use of devices containing antimicrobials and frequent changing of catheters can reduce incidence 103 . Equally important in the hospital setting is constant surveillance and immediate intervention to prevent sepsis and its progression to septic shock and multiple organ failure.
The US Agency for Healthcare Research and Quality has identified sepsis to be the most expensive condition treated in hospitals in the United States, with annual costs exceeding US$20 billion. Moreover, the US Centers for Medicare and Medicaid Services has imposed substantial financial penalties to hospitals and institutions that fail to adequately recognize and treat sepsis early. Most major academic hospitals use early warning systems to detect early infections and their systemic manifestations. These measures often include evaluation of haemodynamics, urine output, body temperature and mental function — often on an hourly basis. For suspicion of sepsis, early intervention by adequately trained health care providers using broad-spectrum antibiotics and fluid support, often necessitating a transfer to an intensive care unit (ICU), have been shown to result in significant reductions in mortality 14,15 .
What is Septic Shock?
Definition of Septic Shock:
Septic shock is a life-threatening infection in which sepsis progresses to such an extent that your blood pressure drops dangerously low to a systolic blood pressure of less than 90mm/Hg. Septic shock also results in very abnormal circulation and cell metabolism. Septic shock is very dangerous and has a death rate of 50%.
Symptoms include low blood pressure (hypotension) cold, pale and clammy skin nausea, diarrhea, and vomiting and mental confusion. Urine output may also be decreased.
Diagnosis and causes:
Septic shock is indicated by the presence of a systolic blood pressure of less than 90mm/Hg. Septic shock is caused by severe sepsis that has not been treated or is not responding to treatment.
Risk factors and complications:
The main risk factor for septic shock is sepsis that is severe and associated with severe infection and injury. Being very sick in the hospital is a risk factor for sepsis and therefore for septic shock. Complications include respiratory failure, kidney failure, cardiac failure, and ultimately death.
Fluid resuscitation is important and is done to increase the blood pressure. Broad-spectrum intravenous antibiotics are given to treat the infection. Vasopressor medications are administered to raise blood pressure. Oxygen may be given and surgery may sometimes be needed.
In Fig. 1, we show the mortality rate as a function of baseline serum lactate level recorded in patients with severe sepsis with (Septic shock, n = 1098) or without shock (Severe sepsis, n = 643) according to the ALBIOS definition. As shown, mortality increased with increasing baseline lactate, both in patients with septic shock (p < 0.0001) and in patients with severe sepsis without shock (p = 0.008). In the same figure, we show the Shock-3 population, which includes only patients with baseline serum lactate above 2 mmol/L. As shown, 377 patients (34%) previously classified as having septic shock, no longer met the criteria for shock - based on the lactate criterion (Shock-3 definition). The change in the inclusion criteria increased the group of patients with severe sepsis without shock from 643 to 1020 patients. In Fig. 2a we show the probability of survival according to the Sepsis-2 and Sepsis-3 definitions. Of note, at 90 days, survival was significantly lower in the subgroup of patients with septic shock and higher lactate (Shock-3) than in patients with shock that had been defined according to Sepsis 2 criteria (Shock-2) independent from the lactate level (chi-square test p = 0.031).
Mortality according to baseline lactate levels in patients with severe sepsis (light bars) or septic shock (dark bars). Chi-square test: sepsis, p = 0.008 septic shock, p < 0.0001
Probability of survival from randomization to day 90. a Kaplan–Meier estimates for the probability of survival among patients classified by Sepsis-2 versus Shock-2. Mean survival time 66.7 (95% CI 64.1–69.2) vs 56.4 (95% CI54.1–58.7) days. Log rank test p < 0.001. Absolute 90-day mortality 34.1% vs 46.7%, respectively. Chi-square test p < 0.001. b Kaplan–Meier estimates of Sepsis-3 vs Shock-3. Mean survival time 66.3 (95% CI 64.2–68.4) vs 51.6 (95% CI 48.7–54.5) days. Log rank test p < 0.001. Absolute 90-day mortality 35.0% vs 51.9%, respectively. Chi-square p < 0.001). c Kaplan–Meier estimates for the probability of survival in patients defined by Shock-2, treated with albumin versus crystalloids. Mean survival time 57.9 (95% CI 54.7–61.1) vs 54.9 (95% CI 51.7–58.2). Log rank test p = 0.082. Absolute 90-day mortality 43.5% vs 49.9% (absolute risk reduction 6.3%, risk ratio 0.89, 95% CI 0.79–0.99). Chi-square test p = 0.04. d Kaplan–Meier estimates for the probability of survival in patients defined by Shock-3, treated with albumin versus crystalloids. Mean survival time: 52.9 (95% CI 48.6–57.1) vs 50.4 (95% CI 46.4–54.4). Log rank test p = 0.246. Absolute 90-day mortality 48.7% vs 54.9% (absolute risk reduction 6.2%, risk ratio 0.88, 95% CI 0.75–1.02). Chi-square test p = 0.11
Patients with septic shock
In Table 2, we compare several baseline physiological and clinical variables recorded following the Shock-2 versus Shock-3 definition. The application of the new classification decreased the population with septic shock by about 34% and increased its severity. Indeed, besides the higher serum lactate levels dictated by the definition criteria, patients defined by Shock-3 had a significantly higher mortality rate (absolute mortality difference of 5.2%), higher SOFA scores and higher Simplified Acute Physiology (SAPS)-II scores. In addition, they had a significantly lower platelet count, a more positive fluid balance at 6 h and received a larger amount of fluid resuscitation in the first 24 h.
Patients without shock
The reclassification of 377 patients from the “septic shock” to the “severe sepsis without shock” group increased the size of the latter by nearly 60%. Besides the differences linked to the new criteria (e.g., all 377 patients transferred had, by definition, norepinephrine infusion), all the other statistically significant differences that we found do not appear clinically relevant (mean arterial pressure difference 2 mmHg, central venous pressure difference 0.5 mmHg, lactate difference 0.5 mmol/L and pH difference 0.01, results not shown). Mortality was also similar between the subgroup of patients with sepsis based on the Sepsis-2 and Sepsis-3 definitions (34.7% vs 35.5%).
Sepsis and albumin
The results of the ALBIOS study indicated that the use of albumin in addition to crystalloids, as compared with the use of crystalloids alone, in patients with severe sepsis or septic shock during their stay in the ICU did not provide a survival benefit at 90 days, despite improvements in hemodynamic variables.
Patients defined by Shock-2
In Fig. 2a, b, we compare the survival probability of patients defined by Shock-2 and Shock-3 relative to patients defined by Sepsis-2 and Sepsis-3. As shown, in both cases, survival was significantly higher in patients with sepsis compared to patients with shock. In Fig. 2c, we compare the effect of albumin versus crystalloids in patients defined by Shock-2 and Shock-3. As shown, in the population defined by Shock-2, the mean survival days are not significantly different between albumin and control treated patients (log rank test p = 0.08) however, the absolute mortality rate at 90 days is significantly different (43.5% vs 49.9%, absolute risk reduction 6.3%, risk ratio 0.89, 95% CI 0.79–0.99, Chi-square test p = 0.04). In patients defined by Shock-3, the mortality rate was 48.7% in the albumin group and 54.9% in the control group (absolute risk reduction 6.2%, risk ratio 0.88, 95% CI 0.75–1.02). The mortality difference, however, was not statistically significant (p = 0.11), nor was the mean number of survival days (p = 0.246).
- Structure of an ICU: Physician Roles, Procedures, & Cardiopulmonary Resuscitation (CPR)
- Medical Decision-Making & Establishing Goals of Care
- Sepsis, Severe Sepsis, and Septic Shock
- Breathing Support for Respiratory Failure
- Sedation and Pain Management & Weaning
- Daily Exercise and Rehabilitation
- After the ICU: Long-Term Care & Life After Surviving Critical Illness
- Additional Resources
Sepsis describes a syndrome that occurs when severe infection results in critical illness and affects 750,000 Americans annually. Sepsis occurs when a bacterial, viral, or fungal infection causes a significant response from the body’s immune system, causing a high heart rate, fever, or fast breathing. Severe sepsis develops when the infection causes organ damage. Septic shock is the most severe form in which the infection causes low blood pressure, resulting in damage to multiple organs. About three in every 10 patients with severe sepsis, and half of those with septic shock, die in the hospital.
Consider asking the following questions:
“Does my loved one have sepsis or septic shock?”
“Do we know what organism is causing the infection in my loved one?”
“Do we know where the infection came from?”
“How well are my loved one’s organs working?”
Antibiotics and intravenous (IV) fluids are two of the most important treatments for sepsis. Studies have shown that delays in receiving the right antibiotics can double the risk of death. Patients are usually started on antibiotics that treat many different types of bacteria—“broad-spectrum antibiotics”—until test results are available to help physicians select antibiotics that treat the specific bacteria causing the
illness—“narrowing antibiotics”. These tests are often referred to as “cultures”, where bodily fluids such as blood, urine, and phlegm, are sent to the laboratory to identify disease-causing bacteria. Preliminary results from cultures may be available within 24 to 48 hours final results from these tests often take several days.
Patients with sepsis often require many liters of IV fluids. In patients with septic shock, however, IV fluids may not be enough to keep their blood pressure in a safe range. In those cases, patients may need a central venous catheter in order to receive specific medicines to increase blood pressure.
This Intensive Care Unit (ICU) guide for patients and families is intended to provide general information about adult ICUs. The guide is for informational purposes only and is not a substitute for the advice or counsel of one’s personal healthcare provider.
The American Thoracic Society improves global health by advancing research, patient care, and public health in pulmonary disease, critical illness, and sleep disorders. Founded in 1905 to combat TB, the ATS has grown to tackle asthma, COPD, lung cancer, sepsis, acute respiratory distress, and sleep apnea, among other diseases.
AMERICAN THORACIC SOCIETY
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The Link Between Septicemia, Sepsis, And E.Coli: How Can Escherichia Coli Cause A Blood Infection?
Whenever anyone has to stay in the hospital for a long time, the potential of hospital-acquired infections will be on the medical staff's radar.
These infections, also called nosocomial infections, are basically what their name suggests — any infection specifically acquired at a hospital. Sometimes, hospital-acquired infections are caused by bacteria that primarily spread in healthcare settings, while other bugs could be picked up anywhere. Some of the more dramatic infections that you have probably already heard of would be MRSA (methicillin-resistant Staphylococcus aureas), or sepsis. These are both common occurrences in the hospital. The longer your stay at a hospital, the more likely you are to catch one of these nasty bugs.
It is important you for you to realize, as a patient, that a hospital is not a place where you want to stay for longer than your doctor sees fit. Many patients do not mind staying in the hospital because they may worry about going home to care for themselves after a complication surgical procedure, but after reading this article, hopefully you will be more aware of the dangers and see that the risks are not worth the reward. In turn, you'll be itching to go home as soon as possible.
What exactly are septicemia and sepsis?
Normally, our blood is housed in a mostly closed environment within our arteries and veins. I say "mostly" closed here, simply because the body does have some areas where the walls are thinner to allow blood to pass through the vessel walls and give tissues the vital nutrients they need to survive. In your biology classes, you may remember these junctions are referred to as capillaries.
This physiological adaption is a very important reason we are alive, but these sites are also a gateway for a number of bacteria that can enter the blood stream. Bacteria are able to enter the blood in a number of different ways. Any common injury that you may sustain, like scraping your knee after a fall or cutting yourself accidentally with a knife, could be a vector for bacteria to enter your bloodstream.
In all likelihood, however, you were able to avoid a trip to the hospital in those circumstances. This is because upon damage along the blood musculature, the blood vessels and immune system launch their own defense against any foreign particles like bacteria or viruses that may enter your blood and prevent the infection from traveling further throughout your body.
When the entry point is opened for a prolonged period of time for whatever reason, the risk of an opportunistic infection that enters the bloodstream and migrates to different parts of your body rises significantly.
Some of the most common reasons behind this increased risk of infection for patients occupying hospital beds would be intravenous lines (IVs) or Foley catheters. Even if hospitals have strict measures in place to limit the amount of time a patient is able to have an open IV access line or how long they are able to leave a catheter in place before needing to remove it, our bodies are unable to adequately defend against all possible infections in some cases — and then, a patient will develop sepsis.
If the causative bacteria are able to penetrate through the first line of defense, the body will still be able to launch an attack against the microbes, but the responses will be much more dramatic. The sympathetic nervous system will be activated, the one responsible for “fight” or “flight” responses, and your body will go into a biological war against these bacteria.
As the sepsis progresses, the level of consciousness could soon be affected and the number of white blood cells will either be very high or very low. This stage, which is called septic shock, demands very significant medical intervention, because without continuously monitoring vital signs like blood pressure, heart rate, and saturation levels and without antibiotics, the patient will likely die.
Now that I may have fully terrified you about the next time you go to the hospital, I’ll bring you some better news in this next section. True, there is always a chance that you could develop sepsis, but doctors are trained to monitor for early signs of sepsis and intervene as the earliest signs to prevent life-threatening complications from developing. We may not always be successful, but most patients are able to enter and leave the hospital without incident.
Is E. Coli something to worry about?
You have almost certainly already heard of E. Coli before, in the news or online. The most likely news story about E. Coli (full name Escherichia coli) would involve some type of contaminated food that an unfortunate customer ingested — but you may not actually be aware of where else E. coli could be found.
E. Coli is a common bacterium that is normally found within the human intestines, as well as those of other warm-blooded organisms. There are a few different strains of E. coli but most of them are completely harmless. A few of strains of E. Coli are able to cause more severe food poisoning incidents.
E. coli is also one of the most abundant organisms within our intestines you may not have known, for instance, that up to 70 percent of the bacteria naturally found within our intestines are E. Coli. These microorganisms are also likely to be found on our skin. The fact that E. Coli is so very common is also why E. Coli can be considered to be one of the most likely causative organisms that could lead to sepsis.
An IV line or catheter could become infected with this bacterium for a number of different reasons.
- Such an infection could be from poor hygiene on the part of the medical staff. It is recommended that doctors, nurses and physiotherapists change gloves every time they meet with a new patient, but that may not always be possible. Even when it is, you will always find those who do not follow protocol.
- Patients could also potentially infect themselves by touching the tubes or even trying to remove them, including while they are sleeping.
- Bed sheets or medical instruments are also a potential source of these infections, whether they are touched by someone else, you, or simply not cleaned frequently enough.
Doctors and other medical professionals try to prevent these opportunistic hospital infections from occurring by limiting the amount of time a patient requires the types of medical interventions that increase the risk of hospital-acquired infections. Time limits on IV lines and catheters are recommended and bed sheets and bandages should be changed routinely to make sure everything stays as sterile as possible.
Even if ideal protocols are followed, however, there is no guarantee that a person could still not end up with septicemia or sepsis during a hospital stay.
If it is suspected that you may have developed sepsis, the most important thing to do is to begin medical treatment as quickly as possible. Antibiotics must be given in an IV line to be as strong and fast-acting as possible. Patients should also be given fluids and their blood should be tested to try to identify the organism causing the infection. This will allow doctors to use specific antibiotics designed to be most effective against that organism.
Most patients will be able to make a full recovery from a mild case of sepsis, but if the sepsis is a very severe, a patient could suffer from septic shock. This is when they may lose consciousness and fall into a coma. If this true medical emergency were to occur, the mortality rate is close to 40 percent.