Жұқпалы инфекция салдарынан қан қысымының қауіпті түрде төмендеуі

Dangerously low blood pressure due to damage from an organ infection

Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis 3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by requiring a vasopressor to maintain a mean arterial pressure of 65 mm Hg or greater and having serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. The primary infection is most commonly caused by bacteria, but also may be by fungi, viruses or parasites. It may be located in any part of the body, but most commonly in the lungs, brain, urinary tract, skin or abdominal organs. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and death.

Septic shock is a result of a systemic response to infection or multiple infectious causes. The precipitating infections that may lead to septic shock if severe enough include but are not limited to appendicitis, pneumonia, bacteremia, diverticulitis, pyelonephritis, meningitis, pancreatitis, necrotizing fasciitis, MRSA and mesenteric ischemia. According to the earlier definitions of sepsis updated in 2001, sepsis is a constellation of symptoms secondary to an infection that manifests as disruptions in heart rate, respiratory rate, temperature, and white blood cell count. If sepsis worsens to the point of end organ dysfunction (kidney 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 criterion has been met for septic shock.

The pathophysiology of septic shock is not entirely understood, but it is known that a key role in the development of severe sepsis is played by an immune and coagulation response to an infection. Both pro inflammatory and anti inflammatory responses play a role in septic shock. Septic shock involves a widespread inflammatory response that produces a hypermetabolic effect. This is manifested by increased cellular respiration, protein catabolism, and metabolic acidosis with a compensatory respiratory alkalosis. followed by endotoxin producing gram negative bacteria, although fungal infections are an increasingly prevalent cause of septic shock. Toxins produced by pathogens cause an immune response; in gram negative bacteria these are endotoxins, which are bacterial membrane lipopolysaccharides (LPS).

In gram positive bacteria, these are exotoxins or enterotoxins, which may vary depending on the species of bacteria. These are divided into three types. Type I, cell surface active toxins, disrupt cells without entering, and include superantigens and heat stable enterotoxins. Type II, membrane damaging toxins, destroy cell membranes in order to enter and include hemolysins and phospholipases. Type III, intracellular toxins or A/B toxins interfere with internal cell function and include shiga toxin, cholera toxin, and anthrax lethal toxin. (note that Shigella and Vibrio cholerae are Gram negative organisms).

In gram negative sepsis, free LPS attaches to a circulating LPS binding protein, and the complex then binds to the CD14 receptor 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). This signaling results in the activation of nuclear factor kappaB (NF κB), which leads to transcription of a number of genes that trigger a proinflammatory response. It was the result of significant activation of mononuclear cells and synthesis of effector cytokines. It also results in profound activation of mononuclear cells and the 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. There, they 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. In response to inflammation, a compensatory reaction of production of anti inflammatory substances such as IL 4, IL 10 antagonists, IL 1 receptor, and cortisol occurs. This is called compensatory anti inflammatory response syndrome (CARS). Both the inflammatory and anti inflammatory reactions are responsible for the course of sepsis and are described as MARS (Mixed Antagonist Response Syndrome). The aim of these processes is to keep inflammation at an appropriate level. CARS often leads to suppression of the immune system, which leaves patients vulnerable to secondary infection. Unless the underlying infection (and LPS overload) is rapidly brought under control, the patient usually dies. The ability of TLR4 to respond to a distinct LPS species are clinically important. Pathogenic bacteria may employ LPS with low biological activity to evade proper recognition by the TLR4/MD 2 system, dampening the host immune response and increasing the risk of bacterial dissemination. On the other hand, such LPS would not be able to induce septic shock in susceptible patients, rendering septic complications more manageable. Yet, defining and understanding how even the smallest structural differences between the very similar LPS species may affect the activation of the immune response may provide the mechanism for the fine tuning of the latter and new insights to immunomodulatory processes.

Treatment guidelines call for the administration of broad spectrum antibiotics within the first hour following recognition of septic shock. Prompt antimicrobial therapy is important, as risk of dying increases by approximately 10% for every hour of delay in receiving antibiotics. Norepinephrine is the preferred vasopressor, while epinephrine may be added to norepinephrine when needed. Low dose vasopressin also may be used as an addition to norepinephrine, but is not recommended as a first line treatment. Dopamine may cause rapid heart rate and arrhythmias, and is only recommended in combination with norepinephrine in those with slow heart rate and low risk of arrhythmia. In the initial treatment of low blood pressure in septic shock, the goal of vasopressor treatment is a mean arterial pressure (MAP) of 65 mm Hg.

Methylene blue has been found to be useful for this condition. Although use of methylene blue has mostly been in adults it has also been shown to work in children. Its mechanism of action is thought to be via the inhibition of the nitric oxide cyclic guanosine monophosphate pathway. This pathway is excessively activated in septic shock. Methylene blue has been found to work in cases resistant to the usual agents. This effect was first reported in the early 1990s.

While there is tentative evidence for β Blocker therapy to help control heart rate, evidence is not significant enough for its routine use. There is tentative evidence that steroids may be useful in improving outcomes. Tentative evidence exists that Polymyxin B immobilized fiber column hemoperfusion may be beneficial in treatment of septic shock. Trials are ongoing and it is currently being used in Japan and Western Europe. Recombinant activated protein C (drotrecogin alpha) in a 2011 Cochrane review was found not to decrease mortality and to increase bleeding, and thus, was not recommended for use. Drotrecogin alfa (Xigris), was withdrawn from the market in October 2011.

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 U. S. Centers for Disease Control, septic shock is the thirteenth leading cause of death in the United States and the most frequent cause of death 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 may 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 fungemia; sepsis, severe sepsis or sepsis syndrome; septic shock, refractory septic shock, multiple organ dysfunction syndrome, and death. 35% of septic shock cases derive from urinary tract infections, 15% from the respiratory tract, 15% from skin catheters (such as IVs), and more than 30% of all cases are idiopathic in origin. The mortality rate from sepsis, especially if it is not treated rapidly with the needed medications in a hospital, is approximately 40% in adults and 25% in children. It is significantly greater when sepsis is left untreated for more than seven days.