Septic shock is a potentially fatal medical condition that occurs when

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

, which is organ injury or damage in response to

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

, 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 An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication, that tends to raise low blood pressure. Some antihypotensive drugs act as vasoconstrictors to i ...

to maintain a mean arterial pressure of 65 mm Hg or greater and having serum

lactate Lactate may refer to: * Lactation, the secretion of milk from the mammary glands * Lactate, the conjugate base of lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with w ...

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 Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

, but also may be by

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...

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 The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the to ...

. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and

death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

. Frequently, people with septic shock are cared for in

intensive care units 220px, Intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensi ...

. It most commonly affects children, immunocompromised individuals, and the elderly, as their

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

s cannot deal with infection as effectively as those of healthy adults. The

mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...

from septic shock is approximately 25–50%.

Causes

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 Appendicitis is inflammation of the appendix. Symptoms commonly include right lower abdominal pain, nausea, vomiting, and decreased appetite. However, approximately 40% of people do not have these typical symptoms. Severe complications of a r ...

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...

bacteremia Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the blood. Blood is normally a sterile environment, so the detection of microbe ...

diverticulitis Diverticulitis, specifically colonic diverticulitis, is a gastrointestinal disease characterized by inflammation of abnormal pouches— diverticula—which can develop in the wall of the large intestine. Symptoms typically include lower abdomi ...

pyelonephritis Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications ...

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic p ...

, 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.

Pathophysiology

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 Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism ...

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. Most cases of septic shock are caused by gram-positive bacteria, 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

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O- antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the out ...

s (LPS).

Gram-positive

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

hemolysin Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acq ...

s and phospholipases. Type III, intracellular toxins or A/B toxins interfere with internal cell function and include

shiga toxin Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origi ...

, cholera toxin, and anthrax lethal toxin. (note that ''Shigella'' and ''Vibrio cholerae'' are Gram negative organisms).

Gram-negative

In gram-negative sepsis, free LPS attaches to a circulating LPS-binding protein, and the complex then binds to the

CD14 CD14 (cluster of differentiation 14) is a human protein made mostly by macrophages as part of the innate immune system. It helps to detect bacteria in the body by binding lipopolysaccharide (LPS), a pathogen-associated molecular pattern (PAMP). ...

receptor on

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

s, and

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

s. 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 Toll-like receptor 4 is a protein that in humans is encoded by the ''TLR4'' gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an ...

). 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 The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

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 Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the '' zona fasciculata'' of the adrenal cortex in the adrenal g ...

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. It was once thought that SIRS or CARS could predominate in a septic individual, and it was proposed that CARS follows SIRS in a two-wave process. It is now believed that the systemic inflammatory response and the compensatory anti-inflammatory response occur simultaneously. 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, activation causing systemic leukocyte adhesion and diffuse alveolar capillary damage in the lung, and activation of the coagulation system culminating in

disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...

(DIC). The hypoperfusion 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 other organ systems. Recently, severe damage to liver ultrastructure has been noticed from treatment with cell-free toxins of

Salmonella ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are '' Salmonella enterica'' and '' Salmonella bongori''. ''S. enterica'' is the type species and is ...

. 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 An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which coul ...

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

may provide the mechanism for the fine tuning of the latter and new insights to immunomodulatory processes.

Diagnosis

According to current guidelines, requirements for diagnosis with sepsis are "the presence (probable or documented) of infection together with systemic manifestations of infection". These manifestations may include: *

Tachypnea Tachypnea, also spelt tachypnoea, is a respiratory rate greater than normal, resulting in abnormally rapid and shallow breathing. In adult humans at rest, any respiratory rate of 1220 per minute is considered clinically normal, with tachypnea b ...

(fast rate of breathing), which is defined as more than 20 breaths per minute, or when testing blood gas, a less than 32 mm Hg, which signifies hyperventilation * White blood cell count either significantly low (< 4000 cells/mm³), or elevated (> 12000 cells/mm³) *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

(rapid heart rate), which in sepsis is defined as a rate greater than 90 beats per minute * Altered body

temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer. Thermometers are calibrated in various temperature scales that historically have relied o ...

Fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

> or hypothermia < Documented evidence of infection, may include positive

blood culture A blood culture is a medical laboratory test used to detect bacteria or fungi in a person's blood. Under normal conditions, the blood does not contain microorganisms: their presence can indicate a bloodstream infection such as bacteremia ...

, signs of

on chest x-ray, or other radiologic or laboratory evidence of infection. Signs of end-organ dysfunction are present in septic shock, including

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, liver dysfunction, changes in mental status, or elevated serum

. Septic shock is diagnosed if there is low blood pressure (BP) that does not respond to treatment. This means that intravenous fluid administration alone is not enough to maintain a patient's BP. Diagnosis of septic shock is made when systolic blood pressure is less than 90 mm Hg, a

mean arterial pressure In medicine, the mean arterial pressure (MAP) is an average blood pressure in an individual during a single cardiac cycle. MAP is altered by cardiac output and systemic vascular resistance. Testing Mean arterial pressure can be measured direc ...

(MAP) is less than 70 mm Hg, or a systolic BP decrease of 40 mm Hg or more without other causes for low BP.

Definition

Septic shock is a subclass of distributive shock, a condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate blood supply to the body tissues, resulting in

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...

and organ dysfunction. Septic shock refers specifically to distributive shock due to

as a result of infection. Septic shock may be defined as sepsis-induced low blood pressure that persists despite treatment with intravenous fluids. Low blood pressure reduces tissue

perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...

pressure, causing the

tissue hypoxia Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either '' generalized'', affecting the whole body, or ''local'', affecting a region of the bo ...

that is characteristic of shock.

Cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

released in a large scale inflammatory response result in massive vasodilation, increased

capillary permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells (lymph ...

, decreased

systemic vascular resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be c ...

, and low blood pressure. Finally, in an attempt to offset decreased blood pressure, ventricular dilatation and myocardial dysfunction occur. Septic shock may be regarded as a stage of SIRS (Systemic Inflammatory Response Syndrome), in which sepsis, severe sepsis and multiple organ dysfunction syndrome (MODS) represent different stages of a pathophysiological process. If an organism cannot cope with an infection, it may lead to a systemic response - sepsis, which may further progress to severe sepsis, septic shock, organ failure, and eventually, result in death.

Treatment

Treatment primarily consists of the following: # Giving

intravenous fluids Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...

# Early antibiotic administration # Early goal directed therapy # Rapid source identification and control # Support of major organ dysfunction

Fluids

Because lowered blood pressure in septic shock contributes to poor perfusion, fluid resuscitation is an initial treatment to increase blood volume. Patients demonstrating sepsis-induced hypoperfusion should be initially resuscitated with at least 30 ml/kg of intravenous crystalloid within the first three hours. Crystalloids such as

normal saline Saline (also known as saline solution) is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By injection into a vein ...

and

lactated Ringer's solution Ringer's lactate solution (RL), also known as sodium lactate solution, Lactated Ringer’s, and Hartmann's solution, is a mixture of sodium chloride, sodium lactate, potassium chloride, and calcium chloride in water. It is used for replacing f ...

are recommended as the initial fluid of choice, while the use of colloid solutions such as

hydroxyethyl starch Hydroxyethyl starch (HES/HAES), sold under the brand name Voluven among others, is a nonionic starch derivative, used as a volume expander in intravenous therapy. The use of HES on critically ill patients is associated with an increased risk of ...

have not shown any advantage or decrease in mortality. When large quantities of fluids are given, administering

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...

has shown some benefit. However, too high of a rate of fluid infusion can be more risky; the particular type of fluid's flow rate must be closely monitored, along with the patient's condition and vital signs.

Antibiotics

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. Time constraints do not allow the culture, identification, and testing for antibiotic sensitivity of the specific microorganism responsible for the infection. Therefore, combination antimicrobial therapy, which covers a wide range of potential causative organisms, is tied to better outcomes. Antibiotics should be continued for 7–10 days in most patients, though treatment duration may be shorter or longer depending on clinical response.

Vasopressors

Among the choices for vasopressors,

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

is superior to

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

in septic shock. 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 Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

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

(MAP) of 65 mm Hg. In 2017, the FDA approved

angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...

injection for intravenous infusion to increase blood pressure in adults with septic or other distributive shock.

Methylene blue

Methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...

has been found to be useful for this condition.Jang DH, Nelson LS, Hoffman RS (2013) Methylene blue for distributive shock: a potential new use of an old antidote. J Med Toxicol 9(3):242-249Baldo CF, Silva LM, Arcencio L, Albuquerque AAS, Celotto AC, Basile-Filho A, Evora PRB (2018) Why Methylene Blue have to be always present in the tocking of emergency antidotes. Curr Drug Targets 19(13):1550-1559McCartney SL, Duce L, Ghadimi K (2018) Intraoperative vasoplegia: methylene blue to the rescue! Curr Opin Anaesthesiol. 31(1):43-49Booth AT, Melmer PD, Tribble B, Mehaffey JH, Tribble C (2017) Methylene blue for vasoplegic syndrome. Heart Surg Forum 20(5):E234-E238 Although use of methylene blue has mostly been in adults it has also been shown to work in children.Rutledge C, Brown B, Benner K, Prabhakaran P, Hayes L (2015) A novel use of methylene blue in the pediatric ICU. Pediatrics 136(4):e1030-4Volpon LC, Evora PRB, Teixeira GD, Godinho M, Scarpelini S, Carmona F, Carlotti APCP (2018) Methylene blue for refractory shock in polytraumatized patient: A case report. J Emerg Med 55(4):553-558 Its mechanism of action is thought to be via the inhibition of the

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ...

cyclic guanosine monophosphate Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases ...

pathway.Da Silva PS, Furtado P (2018) Methylene blue to treat refractory latex-induced anaphylactic shock: a case report. A A Pract 10(3):57-60 This pathway is excessively activated in septic shock. Methylene blue has been found to work in cases resistant to the usual agents.Lo JC, Darracq MA, Clark RF (2014) A review of methylene blue treatment for cardiovascular collapse. J Emerg Med 46(5):670-679 This effect was first reported in the early 1990s.Schneider F, Lutun P, Hasselmann M, Stoclet JC, Tempé JD (1992) Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations. Intensive Care Med 18(5):309-11Preiser JC, Lejeune P, Roman A, Carlier E, De Backer D, Leeman M, Kahn RJ, Vincent JL (1995) Methylene blue administration in septic shock: a clinical trial. Crit Care Med 23(2):259-264

Other

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 Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...

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.

Epidemiology

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 Hospice care is a type of health care that focuses on the palliation of a terminally ill patient's pain and symptoms and attending to their emotional and spiritual needs at the end of life. Hospice care prioritizes comfort and quality of life b ...

care facilities) have 2-4 times the rate of bacteremia than primary care centers, 75% of which are

hospital-acquired infections A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is ...

. 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 Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

), 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.

References

External links

{{DEFAULTSORT:Septic Shock Medical emergencies Intensive care medicine Causes of death Sepsis