severe sepsis

WordNet

1. very bad in degree or extent; "a severe worldwide depression"; "the house suffered severe damage"
2. unsparing and uncompromising in discipline or judgment; "a parent severe to the pitch of hostility"- H.G.Wells; "a hefty six-footer with a rather severe mien"; "a strict disciplinarian"; "a Spartan upbringing" (同)spartan
3. intensely or extremely bad or unpleasant in degree or quality; "severe pain"; "a severe case of flu"; "a terrible cough"; "under wicked fire from the enemys guns"; "a wicked cough" (同)terrible, wicked
4. set or keep apart; "sever a relationship" (同)break_up
5. the presence of pus-forming bacteria or their toxins in the blood or tissues
6. detached by cutting; "cut flowers"; "a severed head"; "an old tale of Anne Bolyn walking the castle walls with her poor cut-off head under her arm" (同)cut_off

PrepTutorEJDIC

1. (人・法律などが)『厳しい』,厳格な / (態度・表情が)厳粛な,いかめしい / (病気などが)『重い』,危険な / (様式・趣味などが)簡素な,じみな,飾りのない / (人の体に)厳しくこたえる,激しい / (試験などが)難しい,厳しい
2. (全体から)…‘を'切断する《+『名』+『from』+『名』》 / (いくつかの部分に)…‘を'分ける《+『名』+『in』(『into』)+『名』》 / 〈関係など〉‘を'断つ / 切れる,分かれる,分裂する
3. 敗血症

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/13 12:25:09」(JST)

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For the genus of flies of this name, see Sepsis (genus).

Sepsis
Blood culture bottles: orange label for anaerobes, green label for aerobes, and yellow label for blood samples from children
Classification and external resources
Pronunciation	/ˈsɛpsᵻs/
Specialty	Infectious disease
ICD-10	A40 – A41
ICD-9-CM	995.91
DiseasesDB	11960
MedlinePlus	000666
Patient UK	Sepsis
MeSH	D018805

Sepsis is a life-threatening condition that arises when the body's response to infection injures its own tissues and organs. Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection. In the very young, old, and people with a weakened immune system, there may be no symptoms of a specific infection and the body temperature may be low or normal rather than high. Severe sepsis is sepsis causing poor organ function or insufficient blood flow. Insufficient blood flow may be evident by low blood pressure, high blood lactate, or low urine output. Septic shock is low blood pressure due to sepsis that does not improve after reasonable amounts of intravenous fluids are given.

Sepsis is caused by an immune response triggered by an infection. The infection is most commonly bacterial, but it can also be from fungi, viruses, or parasites. Common locations for the primary infection include: lungs, brain, urinary tract, skin, and abdominal organs. Risk factors include young or old age, a weakened immune system from conditions such as cancer or diabetes, and major trauma or burns. Diagnosis is based on meeting at least two systemic inflammatory response syndrome (SIRS) criteria due to a presumed infection. Blood cultures are recommended preferably before antibiotics are started; however, infection of the blood is not required for the diagnosis. Medical imaging should be done to look for the possible location of infection. Other potential causes of similar signs and symptoms include: anaphylaxis, adrenal insufficiency, low blood volume, heart failure, and pulmonary embolism among others.

Sepsis is usually treated with intravenous fluids and antibiotics. Antibiotics are typically given as soon as possible. This is often done in an intensive care unit. If fluid replacement is not enough to maintain blood pressure, medications that raise blood pressure can be used. Mechanical ventilation and dialysis may be needed to support the function of the lungs and kidneys, respectively. To guide treatment, a central venous catheter and an arterial catheter may be placed for access to the bloodstream. Other measurements such as cardiac output and superior vena cava oxygen saturation may also be used. People with sepsis need preventive measures for deep vein thrombosis, stress ulcers and pressure ulcers, unless other conditions prevent such interventions. Some might benefit from tight control of blood sugar levels with insulin. The use of corticosteroids is controversial. Activated drotrecogin alfa, originally marketed for severe sepsis, has not been found to be helpful, and was withdrawn from sale in 2011.

Disease severity partly determines the outcome with the risk of death from sepsis being as high as 30%, severe sepsis as high as 50%, and septic shock as high as 80%. The total number of cases worldwide is unknown as there is little data from the developing world. Estimates suggest sepsis affects millions of people a year. In the developed world about 0.2 to 3 per 1000 people get sepsis yearly or about a million cases per year in the United States. Rates of disease have been increasing. Sepsis is more common among males than females. The terms septicemia and blood poisoning referred to the microorganisms or their toxins in the blood and are no longer commonly used. The condition has been described at least since the time of Hippocrates.

Signs and symptoms

Charlotte Cleverley-Bisman, with sepsis from a meningococcal bloodstream infection.

In addition to symptoms related to the provoking cause, sepsis is frequently associated with either fever or low body temperature, rapid breathing, elevated heart rate, confusion, and edema. Early signs are a fast heart rate, decreased urination, and high blood sugar. Signs of established sepsis include confusion, metabolic acidosis (which may be accompanied by faster breathing leading to a respiratory alkalosis), low blood pressure due to decreased systemic vascular resistance, higher cardiac output, and dysfunctions of blood coagulation (where clotting can lead to organ failure).

The drop in blood pressure seen in sepsis may lead to shock. This may result in light-headedness. Bruising or intense bleeding may also occur.

Cause

The most common primary sources of infection resulting in sepsis are the lungs, the abdomen, and the urinary tract. Typically, 50% of all sepsis cases start as an infection in the lungs. No definitive source is found in one third to one half of cases.

Infections leading to sepsis are usually bacterial but can also be fungal or viral. While gram-negative bacteria were previously the most common cause of sepsis, in the last decade 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 infection by Candida species of yeast.

Diagnosis

Systemic inflammatory response syndrome

Finding	Value
Temperature	<36 °C (96.8 °F) or >38 °C (100.4 °F)
Heart rate	>90/min
Respiratory rate	>20/min or PaCO2<32 mmHg (4.3 kPa)
WBC	<4x109/L (<4000/mm³), >12x109/L (>12,000/mm³), or 10% bands

Sepsis Steps. Training tool for teaching the progression of sepsis stages. This should not be used for the identification or treatment of any medical illness.

Early diagnosis is necessary to properly manage sepsis, as initiation of early goal directed therapy is key to reducing mortality from severe sepsis.

Within the first three hours of suspected sepsis, diagnostic studies should include WBCs, measuring serum lactate and obtaining appropriate cultures before starting antibiotics, so long as this does not delay their use by more than 45 minutes. To identify the causative organism(s), at least two sets of blood cultures using bottles with media for aerobic and anaerobic organisms should be obtained, with at least one drawn through the skin and one drawn through each vascular access device (such as an IV catheter) in place more than 48 hours. However, bacteria are present in the blood in only about 30% of cases. Another possible method of detection is by polymerase chain reaction. If other sources of infection are suspected, cultures of these sources, such as urine, cerebrospinal fluid, wounds, or respiratory secretions, should also be obtained, as long as this does not delay the use of antibiotics.

Within six hours, if blood pressure remains low despite initial fluid resuscitation of 30 ml/kg, or if initial lactate is ≥ 4 mmol/L (36 mg/dL), central venous pressure and central venous oxygen saturation should be measured. Lactate should be re-measured if the initial lactate was elevated. Within twelve hours, it is essential to diagnose or exclude any source of infection that would require emergent source control, such as necrotizing soft tissue infection, infection causing inflammation of the abdominal cavity lining, infection of the bile duct, or intestinal infarction. A pierced internal organ (free air on abdominal x-ray or CT scan); an abnormal chest x-ray consistent with pneumonia (with focal opacification); or petechiae, purpura, or purpura fulminans can also be evident of infection.

If the SIRS criteria are negative it is very unlikely the person has sepsis; if they are positive there is just a moderate probability that the person has sepsis.

Definitions

According to the American College of Chest Physicians and the Society of Critical Care Medicine, there are different levels of sepsis: sepsis, severe sepsis, and septic shock.

• Systemic inflammatory response syndrome (SIRS) is the presence of two or more of the following: abnormal body temperature, heart rate, respiratory rate or blood gas, and white blood cell count.
• Sepsis is defined as SIRS in response to an infectious process.
• Severe sepsis is defined as sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion (manifesting as hypotension, elevated lactate, or decreased urine output).
• Septic shock is severe sepsis plus persistently low blood pressure despite the administration of intravenous fluids.

End-organ dysfunction

Examples of end-organ dysfunction include the following:

• Lungs: acute respiratory distress syndrome (ARDS) (PaO₂/FiO₂ < 300)
• Brain: encephalopathy symptoms including agitation, confusion, coma; causes may include ischemia, hemorrhage, formation of blood clots in small blood vessels, microabscesses, multifocal necrotizing leukoencephalopathy
• Liver: disruption of protein synthetic function manifests acutely as progressive disruption of blood clotting due to an inability to synthesize clotting factors and disruption of metabolic functions leads to impaired bilirubin metabolism, resulting in elevated unconjugated serum bilirubin levels
• Kidney: low urine output or no urine output, electrolyte abnormalities, or volume overload
• Heart: systolic and diastolic heart failure, likely due to chemical signals that depress myocyte function, cellular damage, manifest as a troponin leak (although not necessarily ischemic in nature)

More specific definitions of end-organ dysfunction exist for SIRS in pediatrics.

• Cardiovascular dysfunction (after fluid resuscitation with at least 40 ml/kg of crystalloid)
  • hypotension with blood pressure < 5th percentile for age or systolic blood pressure < 2 standard deviations below normal for age, OR
  • vasopressor requirement, OR
  • two of the following criteria:
    • unexplained metabolic acidosis with base deficit > 5 mEq/L
    • lactic acidosis: serum lactate 2 times the upper limit of normal
    • oliguria (urine output < 0.5 ml/kg/h)
    • prolonged capillary refill > 5 seconds
    • core to peripheral temperature difference > 3 °C
• Respiratory dysfunction (in the absence of cyanotic heart disease or known chronic lung disease)
  • the ratio of the arterial partial-pressure of oxygen to the fraction of oxygen in the gases inspired (PaO₂/FiO₂) < 300 (the definition of acute lung injury), OR
  • arterial partial-pressure of carbon dioxide (PaCO₂) > 65 torr (20 mmHg) over baseline PaCO₂ (evidence of hypercapnic respiratory failure), OR
  • supplemental oxygen requirement of greater than FiO₂ 0.5 to maintain oxygen saturation ≥ 92%
• Neurologic dysfunction
  • Glasgow Coma Score (GCS) ≤ 11, OR
  • altered mental status with drop in GCS of 3 or more points in a patient with developmental delay/intellectual disability
• Hematologic dysfunction
  • platelet count < 80,000/mm³ or 50% drop from maximum in chronically thrombocytopenic patients, OR
  • international normalized ratio (INR) > 2
  • Disseminated intravascular coagulation
• Kidney dysfunction
  • serum creatinine ≥ 2 times the upper limit of normal for age or 2-fold increase in baseline creatinine in patients with chronic kidney disease
• Liver dysfunction (only applicable to infants > 1 month)
  • total serum bilirubin ≥ 4 mg/dl, OR
  • alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal

Consensus definitions, however, continue to evolve, with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience.

Biomarkers

A 2013 systematic review and meta-analysis concluded moderate-quality evidence exists to support use of the procalcitonin level as a method to distinguish sepsis from non-infectious causes of SIRS. The same review found the test's sensitivity to be 77% and the specificity to be 79%. The authors suggested procalcitonin may serve as a helpful diagnostic marker for sepsis, but cautioned that its level alone cannot definitively make the diagnosis. 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. However, this same review concluded that SuPAR has prognostic value as higher SuPAR levels are associated with an increased rate of death in those with sepsis.

Differential diagnosis

The differential diagnosis for sepsis is broad and has to look at (to exclude) the noninfectious conditions that can cause the systemic signs of SIRS: alcohol withdrawal, acute pancreatitis, burns, pulmonary embolus, thyrotoxicosis, anaphylaxis, adrenal insufficiency, and neurogenic shock.

Neonatal sepsis

In common clinical usage, neonatal sepsis refers to a bacterial blood stream infection in the first month of life, such as meningitis, pneumonia, pyelonephritis, or gastroenteritis, but neonatal sepsis can also be due to infection with fungi, viruses, or parasites. Criteria with regard to hemodynamic compromise or respiratory failure are not useful because they present too late for intervention.

Pathophysiology

Sepsis is caused by a combination of factors related to the particular invading pathogen(s) and to the status of the host's immune system. The early phase of sepsis characterized by excessive inflammation (which can sometimes result in a cytokine storm) can be followed by a prolonged period of decreased functioning of the immune system. Either of these phases can prove fatal.

Microbial factors

Bacterial virulence factors such as glycocalyx and various adhesins allow colonization, immune evasion, and establishment of disease in the host. Sepsis caused by gram-negative bacteria is thought to be largely due to the host's response to the lipid A component of lipopolysaccharide, also called endotoxin. Sepsis caused by gram-positive bacteria can result from an immunological response to cell wall lipoteichoic acid. Bacterial exotoxins that act as superantigens can also cause sepsis. Superantigens simultaneously bind major histocompatibility complex and T-cell receptors in the absence of antigen presentation. This forced receptor interaction induces the production of pro-inflammatory chemical signals (cytokines) by T-cells.

There are a number of microbial factors which can cause the typical septic inflammatory cascade. An invading pathogen is recognized by its pathogen-associated molecular patterns (PAMPs). Examples of PAMPs include lipopolysaccharides and flagellin in gram-negative bacteria, muramyl dipeptide in the peptidoglycan of the gram-positive bacterial cell wall, and CpG bacterial DNA. These PAMPs are recognized by the innate immune system's pattern recognition receptors (PRRs), which can be membrane-bound or cytosolic. There are four families of PRRs: the toll-like receptors, the C-type lectin receptors, the NOD-like receptors and the RIG-I-like receptors. The association of a PAMP and a PRR will invariably cause a series of intracellular signalling cascades. Consequentially, transcription factors like nuclear factor-kappa B and activator protein-1 will up-regulate the expression of pro-inflammatory and anti-inflammatory cytokines.

Host factors

Cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6 can 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 can lead to intravascular clotting, the formation of blood clots in small blood vessels, and multiple organ failure.

A systemic inflammatory response syndrome can also occur in patients without the presence of infection, for example in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis. 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, and 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.

Management

Early recognition and focused management can improve the outcomes in sepsis. Current professional recommendations include a number of actions ("bundles") to be taken 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 time 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 it was initially raised. A related bundle, the "sepsis six", is in widespread use in the United Kingdom; this requires the administration of antibiotics within an hour of recognition, blood cultures, lactate and hemoglobin determination, urine output monitoring, high-flow oxygen, and intravenous fluids.

Apart from the timely administration of fluids and antibiotics, the management of sepsis also involves surgical drainage of infected fluid collections, and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in lung 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 those with high blood sugar levels, insulin to bring it down to 7.8-10 mmol/L (140–180 mg/dL) is recommended with lower levels potentially worsening outcomes. Medication to prevent deep vein thrombosis and gastric ulcers may also be used.

Antibiotics

In severe sepsis and septic shock, broad-spectrum antibiotics (usually two or a β-lactam antibiotic with broad coverage) are recommended. Some recommend they be given within 1 hour of making the diagnosis stating that for every hour delay in the administration of antibiotics, there is an associated 6% rise in mortality. Others did not find a benefit with early administration. Two sets of blood cultures should be obtained before starting antibiotics if this can be done without delaying the administration of antibiotics.

Several factors determine the most appropriate choice for the initial antibiotic regimen. These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a hospital or community-acquired infection, and which organ systems are thought to be infected. Antibiotic regimens should be reassessed daily and narrowed if appropriate. Treatment duration is typically 7–10 days with the type of antibiotic used directed by the results of cultures.

Intravenous fluids

Intravenous fluids are titrated (measured and adjusted) in response to heart rate, blood pressure, and urine output; restoring large fluid deficits can require 6 to 10 liters of crystalloids in adults. In children an initial amount of 20mL/Kg is reasonable in shock. In cases of severe sepsis and septic shock where a central venous catheter is used to measure blood pressures dynamically, fluids should be administered until the central venous pressure (CVP) reaches 8–12mmHg. Once these goals are met, the central venous oxygen saturation (ScvO2), i.e., the oxygen saturation of venous blood as it returns to the heart as measured at the vena cava, is optimized. If the ScvO2 is less than 70%, blood may be given to reach a hemoglobin of 10 g/dL and then inotropes are added until the ScvO2 is optimized. In those with acute respiratory distress syndrome (ARDS) and sufficient tissue blood fluid, more fluids should be given carefully.

Crystalloid solutions are recommended initially. Crystalloid solutions and albumin are better than other fluids (such as hydroxyethyl starch) in terms of risk of death. Starches also carry an increased risk of acute kidney injury, and need for blood transfusion. Various colloid solutions (such as modified gelatin) carry no advantage over crystalloid. Albumin also appears to be of no benefit over crystalloids. Packed red blood cells are recommended to keep the hemoglobin levels between 70 and 90 g/L. A 2014 trial; however, found no difference between a target hemoglobin of 70 or 90 g/L.

Vasopressors

If the person has been sufficiently fluid resuscitated but the mean arterial pressure is not greater than 65 mmHg, vasopressors are recommended. Norepinephrine (noradrenaline) is recommended as the initial choice. If a single vasopressor is not enough to raise the blood pressure, epinephrine (adrenaline) or vasopressin may be added. Dopamine is typically not recommended. Dobutamine may be used if heart function is poor or blood flow is insufficient despite sufficient fluid volumes and blood pressure.

Ventilation

Etomidate is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death. The small amount of evidence there is, however, has not found a change in the risk of death with etomidate.

It is recommended that the head of the bed be raised if possible to improve ventilation. Paralytic agents should be avoided unless ARDS is suspected.

Steroids

The use of steroids in sepsis is controversial. Studies do not give a clear picture as to whether and when glucocorticoids should be used. The 2012 Surviving Sepsis Campaign recommends against their use in those with septic shock if intravenous fluids and vasopressors stabilize the person's cardiovascular function. While a 2015 Cochrane review found low quality evidence of benefit.

During critical illness, a state of adrenal insufficiency and tissue resistance to corticosteroids may occur. This has been termed critical illness–related corticosteroid insufficiency. Treatment with corticosteroids might be most beneficial in those with septic shock and early severe ARDS, whereas its role in others such as those with pancreatitis or severe pneumonia is unclear. However, the exact way of determining corticosteroid insufficiency remains problematic. It should be suspected in those poorly responding to resuscitation with fluids and vasopressors. ACTH stimulation testing is not recommended to confirm the diagnosis. The method of stopping glucocorticoid drugs is variable, and it is unclear whether they should be slowly decreased or simply abruptly stopped.

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. It is a step-wise approach, with the physiologic goal of optimizing cardiac preload, afterload, and contractility. It includes giving early antibiotics. It involves monitoring of hemodynamic parameters and specific interventions to achieve key resuscitation targets which include maintaining a central venous pressure between 8-12 mmHg, a mean arterial pressure of between 65-90 mmHg, a central venous oxygen saturation (ScvO₂) greater than 70% and a urine output of greater than 0.5 ml/kg/hour. The goal is to optimize oxygen delivery to tissues and achieve a balance between systemic oxygen delivery and demand. An appropriate decrease in serum lactate may be equivalent to ScvO₂ and easier to obtain.

In the original trial, early goal directed therapy was found to reduce mortality from 46.5% to 30.5% in those with sepsis, and the Surviving Sepsis Campaign has been recommending its use. However, three more recent large randomized control trials (ProCESS, ARISE, and ProMISe), did not demonstrate a 90-day mortality benefit of early goal directed therapy versus the standard therapy in severe sepsis. It is likely that some parts of EGDT are more important than others. Following these trials the use of EGDT is still considered reasonable.

Newborns

Neonatal sepsis can be difficult to diagnose as newborns may be asymptomatic. If a newborn shows signs and symptoms suggestive of sepsis, antibiotics are immediately started and are either changed to target a specific organism identified by diagnostic testing or discontinued after an infectious cause for the symptoms has been ruled out.

Other

Monoclonal and polyclonal preparations of intravenous immunoglobulin (IVIG) do not lower the rate of death in newborns and adults with sepsis. Evidence for the use of IgM-enriched polyclonal preparations of IVIG is inconsistent. A 2012 Cochrane review concluded that N-acetylcysteine does not reduce mortality in those with SIRS or sepsis and may even be harmful.

Recombinant activated protein C (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high APACHE II score), where it was thought to confer a survival benefit. However, subsequent studies showed that it increased adverse events—bleeding risk in particular—and did not decrease mortality. It was removed from sale in 2011. Another medication known as eritoran also has not shown benefit.

Prognosis

Approximately 20–35% of people with severe sepsis and 30–70% of people with septic shock die. Lactate is a useful method of determining prognosis with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L have a mortality of less than 15%.

There are a number of prognostic stratification systems such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the person's age, underlying condition, and various physiologic variables to yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler and useful in the emergency department environment.

Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most sepsis patients makes the incidence of this difficult to quantify or to study.

Epidemiology

Sepsis causes millions of deaths globally each year and is the most common cause of death in people who have been hospitalized. The worldwide incidence of sepsis 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. Due to it rarely being reported as a primary diagnosis (often being a complication of cancer or other illness), the incidence, mortality, and morbidity rates of sepsis are likely underestimated. A study by the Agency for Healthcare Research and Quality (AHRQ) of selected States found that there were 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) patients, 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 U.S. patients 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 Medicare patients in 2011, septicemia was the second most common principal reason for readmission within 30 days.

Several medical conditions increase a person's susceptibility to infection and developing 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.

History

Personification of septicaemia, carrying a spray can marked 'Poison'.

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. In the eleventh century, Avicenna used the term "blood rot" for diseases linked to severe purulent process. Though severe systemic toxicity had already been observed, it was only in the 19th century that the specific term – sepsis – was used for this condition.

By the end of the 19th century, it was widely believed that microbes produced substances that could injure the mammalian host and that soluble toxins released during infection caused the fever and shock that were commonplace during severe infections. Pfeiffer coined the term endotoxin at the beginning of the 20th century to denote the pyrogenic principle associated with Vibrio cholerae. It was soon realised that endotoxins were expressed by most and perhaps all gram-negative bacteria. The lipopolysaccharide character of enteric endotoxins was elucidated in 1944 by Shear. The molecular character of this material was determined by Luderitz et al. in 1973.

It was discovered in 1965 that a strain of C3H/HeJ mice were immune to the endotoxin-induced shock. The genetic locus for this effect was dubbed Lps. These mice were also found to be hypersusceptible to infection by gram-negative bacteria. These observations were finally linked in 1998 by the discovery of the toll-like receptor gene 4 (TLR 4). Genetic mapping work, performed over a period of five years, showed that TLR4 was the sole candidate locus within the Lps critical region; this strongly implied that a mutation within TLR4 must account for the lipopolysaccharide resistance phenotype. The defect in the TLR4 gene that led to the endotoxin resistant phenotype was discovered to be due to a mutation in the cytoplasm.

Society and culture

Economics

Sepsis was the most expensive condition treated in U.S. hospital stays in 2011, at an aggregate cost of $20.3 billion for nearly 1.1 million hospitalizations. Costs for sepsis hospital stays more than quadrupled since 1997 with an 11.5 percent annual increase. By payer, it was the most costly condition billed to Medicare, the second-most costly billed to Medicaid and the uninsured, and the fourth-most costly billed to private insurance.

Education

A large international collaboration entitled the "Surviving Sepsis Campaign" was established in 2002 to educate people about sepsis and to improve patient outcomes with sepsis. The Campaign has published an evidence-based review of management strategies for severe sepsis, with the aim to publish a complete set of guidelines in subsequent years.

Sepsis Alliance is a charitable organization run by a team of dedicated laypeople and healthcare professionals who share a strong commitment to battling sepsis. The organization was created to raise sepsis awareness among both the general public and healthcare professionals.

Notes

References

External links

Media related to Sepsis at Wikimedia Commons

• Sepsis at DMOZ
• SIRS, Sepsis, and Septic Shock Criteria

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 成人における重症敗血症および敗血症性ショックの評価およびマネージメント evaluation and management of severe sepsis and septic shock in adults
• 2. 敗血症および全身性炎症反応症候群：定義、疫学、および予後 sepsis and the systemic inflammatory response syndrome definitions epidemiology and prognosis
• 3. Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock
• 4. 敗血症の病態生理 pathophysiology of sepsis
• 5. 敗血症に対する治験剤および無効剤 investigational and ineffective therapies for sepsis

English Journal

• Myrrh inhibits LPS-induced inflammatory response and protects from cecal ligation and puncture-induced sepsis.

• Kim MS, Bae GS, Park KC, Koo BS, Kim BJ, Lee HJ, Seo SW, Shin YK, Jung WS, Cho JH, Kim YC, Kim TH, Song HJ, Park SJ.SourceDepartment of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, Republic of Korea.
• Evidence-based complementary and alternative medicine : eCAM.Evid Based Complement Alternat Med.2012;2012:278718. Epub 2011 Aug 2.
• Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of m
• PMID 21826187

Japanese Journal

• 肺炎におけるステロイド療法の功罪 (特集 呼吸器疾患とステロイド療法)

• 山本 洋,横山 俊樹,久保 惠嗣
• 呼吸器内科 19(2), 112-118, 2011-02
• NAID 40018778307

Related Links

• Severe Sepsis and Septic Shock — NEJM - The New ...

Outcome Before the introduction of modern intensive care with the ability to provide vital-organ support, severe sepsis and septic shock were typically lethal. Even with intensive care, rates of in-hospital death from septic shock were ...

• Surviving Sepsis Campaign | Guidelines

The third edition of "Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 " appeared in the February 2013 issues of Critical Care Medicine and Intensive Care Medicine. ...

Related Pictures

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★リンクテーブル★

リンク元	「敗血症」「重症敗血症」
関連記事	「severe」「sever」

「敗血症」

　　[★]

英

sepsis, (昔の概念→)septicemia

関

定義

• 感染症による全身性炎症反応症候群(SIRS)をセプシス(sepsis, 広義の敗血症？)とする
• 感染症の病原体は、一般細菌(グラム陽性菌・陰性菌)、真菌、寄生虫、ウイルスなど
• 皮膚や粘膜の傷とか、種々の臓器にある感染巣から、細菌がリンパ流から血中に入り、全身に播種されて、新たに転移性の感染巣をつくり、重篤な全身症状を引き起こす。

全身性炎症反応症候群の診断基準

• 下記項目のうち2項目以上が当てはまる

• 1. 体温>38℃ or 体温<36℃
• 2. 心拍数>90bpm
• 3. 呼吸数>20回/min or PaCO2<32mmHg
• 4. (白血球数>12,000/ul or 白血球数<4,000/ul) or ( 幼若好中球>10% )　←　ここでいう幼若好中球とは桿状好中球のことである。

敗血症の周辺疾患概念

• 1. 全身性炎症反応症候群 systemic inflammatory response syndrome SIRS

• 発熱や白血球増加などの全身の炎症の徴候によって特徴づけられる病態(SIRSの診断基準に合致する病態)

• 2. 敗血症 sepsis

• SIRSが感染の結果である場合

• 3. 重症敗血症 severe sepsis

• 主要臓器障害を伴う敗血症

• 4. 敗血症性ショック septic shock

• 輸液投与に不応性の低血圧を伴う重症敗血症

• 5. 多臓器機能障害症候群 multiorgan dysfunction syndrome MODS

• 2つ以上の主要臓器の機能異常

• 6. 多臓器不全 multiorgan failure MOF

• 2つ以上の主要臓器の不全状態

病態生理

• LPS

• LPSが血液凝固を促進→血小板、フィブリノゲン、凝固因子消費　→　血栓形成　→　プラスミノゲンを消費して血栓溶解 (FDP産生)　→

→出血傾向　→　皮下出血、歯肉出血、顕微鏡的血尿(出血性敗血症)

原因となる病原体

• 細菌：グラム陽性球菌(ブドウ球菌、レンサ球菌)、グラム陰性桿菌(大腸菌、緑膿菌、肺炎桿菌、プロテウス)
• 真菌：Candida albicans

症状

• 悪寒、戦慄を伴う発熱、頻脈、頻呼吸、全身倦怠感、呼吸困難、意識障害、ショック、乏尿
• 敗血症による多臓器不全で障害を受けやすい臓器：肺、腎臓、心血管系、中枢神経系

• 重症敗血症の40%に急性呼吸促迫症候群を合併

検査

血液検査

• 白血球：12,000/ul以上のことが多い(SIRSの定義)

左方移動、重症例では白血球減少

• 血小板数：血管内凝固に伴い低下
• CRP：基準値以上
• 凝固系・線溶系：凝固能低下、線溶系亢進

培養

• 血液培養
• カテーテルの先端(留置カテーテルがある場合)

治療 (ICU.644)

酸素投与

敗血症における組織の酸素化

• 敗血症では細胞の酸素摂取能が損なわれている　→　重症敗血症患者の組織酸素濃度がなぜ健常者よりも高くなる　(ICU.645)
• 重症敗血症や敗血症性ショックにおいては

敗血症における酸素摂取量(ICU.645)

• 敗血症における酸素摂取量(VO2)の増加は、好中球の活性化の過程(呼吸バースト)で酸素が消費された結果。

初期蘇生

• 重症敗血症や敗血症性ショックの患者に対する最初の6時間の管理目標

• 1.中心静脈庄8-12mmHg
• 2.平均動脈庄≧65mmHg
• 3.尿量≧0.5 mL/kg/h
• 4.SVO2≧70% or SCVO2≧70%

SVO2：混合静脈血酸素飽和度、肺動脈血酸素飽和度

SCVO2：中心静脈血酸素飽和度、上大静脈血酸素飽和度

輸液負荷

• 循環血液量減少が明らかであるか疑われる場合：

• 1. 500-1,000mLの晶質液 or 300-500mLの膠質液を30分かけて投与
• 2. 初期蘇生の目標値に達するまで、または輸液過多寸前になるまで1)を行う。

昇圧薬(ICU.646)

• 1. 輸液負荷を行っても低血圧が持続する場合、ドパミン or ノルアドレナリンを投与

ドパミン：5-20 ug/kg/min：心拍出量増加：腹腔内蔵機の血流減少

ノルアドレナリン：0.2-1.3 ug/kg/min：心拍出量不変、血管収縮

• 2. 1. に不応の場合、パソプレシン

パソプレシン：0.01-0.04 U/min：血管収縮薬：心拍出量減少→心不全の既往で慎重

経験的抗菌薬治療(ICU.646)

• 重症敗血症や敗血症性ショックと診断したら1時間以内に抗菌薬を静脈内投与する
• 抗菌薬投与前に少なくとも2セットの血液検体を採取　→　血液培養＆感受性検査のため
• イミペネム/メロペネムの単剤
• MRSAのリスクリスク有り：イミペネム/メロペネム + バンコマイシン/リネゾリド

コルチコステロイド(ICU.646)

• 昇庄薬を必要とするすべての敗血症性ショック患者に推奨
• ヒドロコルチゾン：200-300mg用を2-3回に分割して静脈内投与もしくは経口投与、7日間継続
• 副腎不全の改善

「重症敗血症」

　　[★]

英

severe sepsis

関

敗血症

「severe」

　　[★]

• adj.

• 重篤な、重症の、重度の、激しい、苛酷な

• 1.

• 厳しい、厳格な。厳密な(⇔mild)。容赦しない、血も涙もない、痛烈な
• ひどい、猛烈な。骨の折れる。過酷な

• 2

• 簡素な、地味な、渋い。厳粛な

関

critically ill、grave、heavily、intense、life-threatening、rampant、serious、seriously、severe disease、severely、strenuous、severeness

　 　 　 　

「sever」

　　[★]

• v.

• 切断する

関

ablate、ablation、amputate、amputation、break、breakage、cleavage、cleave、scission、transection、truncate、truncation