|Classification and external resources|
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. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and death. Its most common victims are children, immunocompromised 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%.
In humans, septic shock has a specific definition requiring several conditions to be met for diagnosis:
- Traditionally, SIRS (systemic inflammatory response syndrome) must first be diagnosed by finding at least any two of the following:
- Tachypnea (high respiratory rate) > 20 breaths per minute, or on blood gas, a PCO2 less than 32 mmHg signifying hyperventilation.
- White blood cell count either significantly low, < 4000 cells/mm3 or elevated > 12000 cells/mm3.
- Heart rate > 90 beats per minute
- Temperature: Fever > 38.0 °C (100.4 °F) or hypothermia < 36.0 °C (96.8 °F)
- However, according to current guidelines, all that is required are "systemic manifestations of infection," broadening the definition beyond the above four.
- Second, there must be sepsis and not an alternative form cause of SIRS. Sepsis requires evidence of infection, which may include positive blood culture, signs of pneumonia on chest x-ray, or other radiologic or laboratory evidence of infection.
- Third, signs of end-organ dysfunction are required such as renal failure, liver dysfunction, changes in mental status, or elevated serum lactate.
- Finally, septic shock is diagnosed if there is refractory hypotension (low blood pressure that does not respond to treatment). This signifies that intravenous fluid administration alone is insufficient to maintain a patient's blood pressure from becoming hypotensive.
A subclass of distributive shock, septic shock refers specifically to decreased tissue perfusion resulting in ischemia and organ dysfunction. Cytokines released in a large scale inflammatory response results in massive vasodilation, increased capillary permeability, decreased systemic vascular resistance, and hypotension. Hypotension reduces tissue perfusion pressure causing tissue hypoxia. Finally, in an attempt to offset decreased blood pressure, ventricular dilatation and myocardial dysfunction will occur.
When bacteria or viruses are present in the bloodstream, the condition is known as bacteremia or viremia. Sepsis is a constellation of symptoms secondary to infection that manifest as disruptions in heart rate, respiratory rate, temperature and white blood cell count. 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, but are not limited to, appendicitis, pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis, and necrotizing fasciitis.
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. Engagement of CD14 (even at doses as minute as 10 pg/mL) results in intracellular signaling via an associated "Toll-like receptor" protein 4 (TLR-4), resulting in profound activation of mononuclear cells and production of potent effector cytokines such as IL-1, IL-6, and TNF-α. TLR-mediated activation helps to trigger the innate immune system to efficiently eradicate invading microbes, but the cytokines they produce also act on endothelial cells and have a variety of effects, including reduced synthesis of anticoagulation factors such as tissue factor pathway inhibitor and thrombomodulin. The effects of the cytokines may be amplified by TLR-4 engagement on endothelial cells.
At high levels of LPS, the syndrome of septic shock supervenes; the same cytokine and secondary mediators, now at high levels, result in systemic vasodilation (hypotension), diminished myocardial contractility, widespread endothelial injury and activation, causing systemic leukocyte adhesion and diffuse alveolar capillary damage in the lung activation of the coagulation system, culminating in disseminated intravascular coagulation (DIC). The hypoperfusion resulting from the combined effects of widespread vasodilation, myocardial pump failure, and DIC causes multiorgan system failure that affects the liver, kidneys, and central nervous system, among others. Severe damage to liver ultrastructure has been recently noticed by treatment with cell-free toxins of Salmonella. Unless the underlying infection (and LPS overload) is rapidly brought under control, the patient usually dies.
Treatment primarily consists of the following.
- Volume resuscitation
- Early antibiotic administration
- Early goal directed therapy
- Rapid source identification and control.
- Support of major organ dysfunction.
- Sequestration of lipopolysaccharides.
Antimediator agents may be of some limited use in severe clinical situations however are controversial:
- Low dose steroids (hydrocortisone) for 5 – 7 days led to improved outcomes.
- Recombinant activated protein C (drotrecogin alpha) in a 2011 Cochrane review was found not to decrease mortality and thus was not recommended for use. Other reviews however comment that it may be effective in those with very severe disease. The first and only activated protein C drug, drotrecogin alfa (Xigris), was voluntarily withdrawn in October 2011 after it failed to show a benefit in patients with septic shock, including the more severe disease subgroups.
A technique that has shown success and is currently used in Japan, if not elsewhere, involves sequestering the lipopolysacharides that effectively cause septic shock. The antibiotic toraymyxin coincidentally does this, but is also too toxic to be administered. The Japanese technique binds this toraymixin to an immobile material like polystyrene, and pass the blood over it, but this isn't always practical. Recent peer-reviewed research has found a substance derived from the very same spermine found in semen, to bind to lipopolysaccharids which, so far, seems to be non-toxic as well.
Sepsis has a worldwide incidence of more than 20 million cases a year, with mortality due to septic shock reaching up to 50 percent even in industrialized countries.
According to the US CDC, septic shock is the 13th leading cause of death in the United States, and the #1 cause of deaths in intensive care units. There has been an increase in the rate of septic shock deaths in recent decades, which is attributed to an increase in invasive medical devices and procedures, increases in immunocompromised patients, and an overall increase in elderly patients. Tertiary care centers (such as hospice care facilities) have 2-4 times the rate of bacteremia than primary care centers, 75% of which are hospital-acquired infections.
The process of infection by bacteria or fungi can result in systemic signs and symptoms that are variously described. Approximately 70% of septic shock cases were once traceable to gram-negative bacteria that produce endotoxins; however, with the emergence of MRSA and the increased use of arterial and venous catheters, gram-positive bacteria are implicated approximately as commonly as bacilli. In rough order of increasing severity, these are bacteremia or fungemic; septicemia; sepsis, severe sepsis or sepsis syndrome; septic shock; refractory septic shock; multiple organ dysfunction syndrome, and death.
The mortality rate from sepsis is approximately 40% in adults, and 25% in children, and is significantly greater when left untreated for more than 7 days.
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