Multiple organ dysfunction syndrome

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Multiple organ dysfunction syndrome
Other namesTotal organ failure, multisystem organ failure, multiple organ failure
CausesInfection, injury, hypermetabolism
Prognosis Case fatality rate 30–100% depending on the number of organs that failed

Multiple organ dysfunction syndrome (MODS) is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis.

Contents

Although Irwin and Rippe cautioned in 2005 that the use of "multiple organ failure" or "multisystem organ failure" should be avoided, [1] both Harrison's (2015) and Cecil's (2012) medical textbooks still use the terms "multi-organ failure" and "multiple organ failure" in several chapters and do not use "multiple organ dysfunction syndrome" at all.

There are different stages of organ dysfunction for certain different organs, both in acute and in chronic onset, whether or not there are one or more organs affected. Each stage of dysfunction (whether it be the heart, lung, liver, or kidney) has defined parameters, in terms of laboratory values based on blood and other tests, as to what it is (each of these organs' levels of failure is divided into stage I, II, III, IV, and V). The word "failure" is commonly used to refer to the later stages, especially IV and V, when artificial support usually becomes necessary to sustain life; the damage may or may not be fully or partially reversible.

Signs and symptoms

Cause

The condition results from infection, injury (accident, surgery), hypoperfusion and hypermetabolism. The primary cause triggers an uncontrolled inflammatory response.[ citation needed ]

Sepsis is the most common cause of multiple organ dysfunction syndrome and may result in septic shock. In the absence of infection, a sepsis-like disorder is termed systemic inflammatory response syndrome (SIRS). Both SIRS and sepsis could ultimately progress to multiple organ dysfunction syndrome. In one-third of the patients, however, no primary focus can be found. [1] Multiple organ dysfunction syndrome is well established as the final stage of a continuum: SIRS + infection → sepsis → severe sepsis → Multiple organ dysfunction syndrome.[ citation needed ]

Currently, investigators are looking into genetic targets for possible gene therapy to prevent the progression to multiple organ dysfunction syndrome. Some authors have conjectured that the inactivation of the transcription factors NF-κB and AP-1 would be appropriate targets in preventing sepsis and SIRS. [2] These two genes are pro-inflammatory. They are essential components of a normal healthy immune response, however, so there is risk of increasing vulnerability to infection, which can also cause clinical deterioration.[ citation needed ]

Pathophysiology

A definite explanation has not been found. Local and systemic responses are initiated by tissue damage. Respiratory failure is common in the first 72 hours. Subsequently, one might see liver failure (5–7 days), gastrointestinal bleeding (10–15 days) and kidney failure (11–17 days). [1]

Gut hypothesis

The most popular hypothesis by Deitch to explain MODS in critically ill patients is the gut hypothesis. [3] Due to splanchnic hypoperfusion and the subsequent mucosal ischaemia there are structural changes and alterations in cellular function. This results in increased gut permeability, changed immune function of the gut and increased translocation of bacteria. Liver dysfunction leads to toxins escaping into the systemic circulation and activating an immune response. This results in tissue injury and organ dysfunction. [1]

Endotoxin macrophage hypothesis

Gram-negative infections in MODS patients are relatively common, hence endotoxins have been advanced as principal mediator in this disorder. It is thought that following the initial event cytokines are produced and released. The pro-inflammatory mediators are: tumor necrosis factor-alpha (TNF-α), interleukin-1, interleukin-6, thromboxane A2, prostacyclin, platelet activating factor, and nitric oxide. [1]

Tissue hypoxia-microvascular hypothesis

As a result of macro- and microvascular changes insufficient supply of oxygen occurs. Hypoxemia causes cell death and organ dysfunction. [1]

Mitochondrial DNA hypothesis

According to findings of Professor Zsolt Balogh and his team at the University of Newcastle (Australia), mitochondrial DNA is the leading cause of severe inflammation due to a massive amount of mitochondrial DNA that leaks into the bloodstream due to cell death of patients who survived major trauma.[ citation needed ]

Mitochondrial DNA resembles bacterial DNA. If bacteria triggers leukocytes, mitochondrial DNA may do the same. When confronted with bacteria, white blood cells, or neutrophil granulocytes, behave like predatory spiders. They spit out a web, or net, to trap the invaders, then hit them with a deadly oxidative blast, forming neutrophil extracellular traps (NETs).[ citation needed ]

This results in catastrophic immune response leading to multiple organ dysfunction syndrome. [4] [5]

Integrated hypothesis

Since in most cases no primary cause is found, the condition could be part of a compromised homeostasis involving the previous mechanisms. [1]

Diagnosis

The European Society of Intensive Care organized a consensus meeting in 1994 to create the "Sepsis-Related Organ Failure Assessment (SOFA)" score to describe and quantitate the degree of organ dysfunction in six organ systems. Using similar physiologic variables the Multiple Organ Dysfunction Score was developed. [1]

Four clinical phases have been suggested:[ citation needed ]

Definition

Multiple dysfunction syndrome is the presence of altered organ function in acutely ill patients such that homeostasis cannot be maintained without intervention. It usually involves two or more organ systems. It calls for an immediate intervention. [1]

Management

At present, there is no drug or device that can reverse organ failure that has been judged by the health care team to be medically and/or surgically irreversible (organ function can recover, at least to a degree, in patients whose organs are very dysfunctional, where the patient has not died;[ citation needed ] and some organs, like the liver or the skin, can regenerate better than others),- with the possible exception of single or multiple organ transplants or the use of artificial organs or organ parts, in certain candidates in specific situations. Therapy, therefore, is usually mostly limited to supportive care, i.e. safeguarding hemodynamics, and respiration. Maintaining adequate tissue oxygenation is a principal target. Starting enteral nutrition within 36 hours of admission to an intensive care unit has reduced infectious complications. [1]

Prognosis

Mortality, though it has lessened to a limited degree, at least in developed countries with timely access to initial and tertiary care, varies where the chance of survival is diminished as the number of organs involved increases. Mortality in MODS from septic shock (which itself has a high mortality of 25–50%), and from multiple traumas, especially if not rapidly treated, appear to be especially severe. If more than one organ system is affected, the mortality rate is still higher, and this is especially the case when five or more systems or organs are affected. Old age is a risk factor in and of itself, and immunocompromised patients, such as with cancer or AIDS or a transplant, are at risk. Prognosis must take into account any co-morbidities the patient may have, their past and current health status, any genetic or environmental vulnerabilities they have, the nature and type of the illness or injury (as an example, data from COVID-19 is still being analyzed, whereas other cases from long-existing illnesses are much better understood), and any resistance to drugs used to treat microbial infections or any hospital-acquired co-infection. Earlier and aggressive treatment, the use of experimental treatments, or at least modern tools such as ventilators, ECMO, dialysis, bypass, and transplantation, especially at a trauma center, may improve outcomes in certain cases, but this depends in part on speedy and affordable access to high-quality care, which many areas lack. Measurements of lactate, cytokines, albumin and other proteins, urea, blood oxygen and carbon dioxide levels, insulin, and blood sugar, adequate hydration, constant monitoring of vital signs, good communication within and between facilities and staff, and adequate staffing, training, and charting are important in MODS, as in any serious illness. [6] [7] [8] [9] [10]

In patients with sepsis, septic shock, or multiple organ dysfunction syndrome that is due to major trauma, the rs1800625 polymorphism is a functional single nucleotide polymorphism, a part of the receptor for advanced glycation end products (RAGE) transmembrane receptor gene (of the immunoglobulin superfamily) and confers host susceptibility to sepsis and MODS in these patients. [11]

History

For many years, some patients were loosely classified as having sepsis or the sepsis syndrome. In more recent years, these concepts have been refined – so that there are specific definitions of sepsis – and two new concepts have been developed: the SIRS and MODS. [1]

Related Research Articles

<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair.

<span class="mw-page-title-main">Peritonitis</span> Medical condition

Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part or the entire abdomen may be tender. Complications may include shock and acute respiratory distress syndrome.

<span class="mw-page-title-main">Shock (circulatory)</span> Medical condition of insufficient blood flow

Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thirst. This may be followed by confusion, unconsciousness, or cardiac arrest, as complications worsen.

<span class="mw-page-title-main">Sepsis</span> Life-threatening organ dysfunction triggered by infection

Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs.

<span class="mw-page-title-main">Septic shock</span> 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%.

<span class="mw-page-title-main">Alcoholic hepatitis</span> Medical condition

Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8-10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severe cases may be treated with glucocorticoids. The condition often comes on suddenly and may progress in severity very rapidly.

<span class="mw-page-title-main">Procalcitonin</span> Precursor of the peptide hormone calcitonin

Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It arises once preprocalcitonin is cleaved by endopeptidase. It was first identified by Leonard J. Deftos and Bernard A. Roos in the 1970s. It is composed of 116 amino acids and is produced by parafollicular cells of the thyroid and by the neuroendocrine cells of the lung and the intestine.

In immunology, systemic inflammatory response syndrome (SIRS) is an inflammatory state affecting the whole body. It is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, it actually has pro- and anti-inflammatory components.

<span class="mw-page-title-main">Acute liver failure</span> Medical condition

Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease, and indicates that the liver has sustained severe damage. The complications are hepatic encephalopathy and impaired protein synthesis. The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.

A cytokine storm, also called hypercytokinemia, is a pathological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Cytokines are a normal part of the body's immune response to infection, but their sudden release in large quantities may cause multisystem organ failure and death.

Distributive shock is a medical condition in which abnormal distribution of blood flow in the smallest blood vessels results in inadequate supply of blood to the body's tissues and organs. It is one of four categories of shock, a condition where there is not enough oxygen-carrying blood to meet the metabolic needs of the cells which make up the body's tissues and organs. Distributive shock is different from the other three categories of shock in that it occurs even though the output of the heart is at or above a normal level. The most common cause is sepsis leading to a type of distributive shock called septic shock, a condition that can be fatal.

<span class="mw-page-title-main">Complement component 5a</span> Protein fragment

C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b fragments. C5b is important in late events of the complement cascade, an orderly series of reactions which coordinates several basic defense mechanisms, including formation of the membrane attack complex (MAC), one of the most basic weapons of the innate immune system, formed as an automatic response to intrusions from foreign particles and microbial invaders. It essentially pokes microscopic pinholes in these foreign objects, causing loss of water and sometimes death. C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of the MAC, attraction of innate immune cells, and histamine release involved in allergic responses. The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of C5a. C5a is a chemotactic agent and an anaphylatoxin; it is essential in the innate immunity but it is also linked with the adaptive immunity. The increased production of C5a is connected with a number of inflammatory diseases.

<span class="mw-page-title-main">Hypoalbuminemia</span> Medical condition

Hypoalbuminemia is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or abnormal distribution between body compartments. Patients often present with hypoalbuminemia as a result of another disease process such as malnutrition as a result of severe anorexia nervosa, sepsis, cirrhosis in the liver, nephrotic syndrome in the kidneys, or protein-losing enteropathy in the gastrointestinal tract. One of the roles of albumin is being the major driver of oncotic pressure in the bloodstream and the body. Thus, hypoalbuminemia leads to abnormal distributions of fluids within the body and its compartments. As a result, associated symptoms include edema in the lower legs, ascites in the abdomen, and effusions around internal organs. Laboratory tests aimed at assessing liver function diagnose hypoalbuminemia. Once identified, it is a poor prognostic indicator for patients with a variety of different diseases. Yet, it is only treated in very specific indications in patients with cirrhosis and nephrotic syndrome. Treatment instead focuses on the underlying cause of the hypoalbuminemia. Albumin is an acute negative phase respondent and not a reliable indicator of nutrition status.

Immune reconstitution inflammatory syndrome (IRIS) is a condition seen in some cases of HIV/AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.

<span class="mw-page-title-main">SOFA score</span> Medical assessment

The sequential organ failure assessment score, previously known as the sepsis-related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems.

End organ damage is severe impairment of major body organs due to high blood pressure or states of low blood pressure or low blood volume. This can present as a heart attack or heart failure, pulmonary edema, neurologic deficits including a stroke, or acute kidney failure.

Capillary leak syndrome, or vascular leak syndrome, is characterized by the escape of blood plasma through capillary walls, from the blood circulatory system to surrounding tissues, muscle compartments, organs or body cavities. It is a phenomenon most commonly witnessed in sepsis, and less frequently in autoimmune diseases, differentiation syndrome, engraftment syndrome, hemophagocytic lymphohistiocytosis, the ovarian hyperstimulation syndrome, viral hemorrhagic fevers, and snakebite and ricin poisoning. Pharmaceuticals, including the chemotherapy medications gemcitabine and denileukin diftitox, as well as certain interleukins and monoclonal antibodies, can also cause capillary leaks. These conditions and factors are sources of secondary capillary leak syndrome.

Ulinastatin, is a glycoprotein that is isolated from healthy human urine or synthetically produced and has molecular weight of 25 - 40kDa. It acts as a urinary trypsin inhibitor (UTI). Highly purified ulinastatin has been clinically used for the treatment of acute pancreatitis, chronic pancreatitis, Stevens–Johnson syndrome, burns, septic shock, and toxic epidermal necrolysis (TEN).

Abdominal compartment syndrome (ACS) occurs when the abdomen becomes subject to increased pressure reaching past the point of intra-abdominal hypertension (IAH). ACS is present when intra-abdominal pressure rises and is sustained at > 20 mmHg and there is new organ dysfunction or failure. ACS is classified into three groups: Primary, secondary and recurrent ACS. It is not a disease and as such it occurs in conjunction with many disease processes, either due to the primary illness or in association with treatment interventions. Specific cause of abdominal compartment syndrome is not known, although some causes can be sepsis and severe abdominal trauma. Increasing pressure reduces blood flow to abdominal organs and impairs pulmonary, cardiovascular, renal, and gastro-intestinal (GI) function, causing obstructive shock, multiple organ dysfunction syndrome and death.

<span class="mw-page-title-main">Pathophysiology of acute respiratory distress syndrome</span>

The pathophysiology of acute respiratory distress syndrome involves fluid accumulation in the lungs not explained by heart failure. It is typically provoked by an acute injury to the lungs that results in flooding of the lungs' microscopic air sacs responsible for the exchange of gases such as oxygen and carbon dioxide with capillaries in the lungs. Additional common findings in ARDS include partial collapse of the lungs (atelectasis) and low levels of oxygen in the blood (hypoxemia). The clinical syndrome is associated with pathological findings including pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of chemical signals and other inflammatory mediators secreted by local epithelial and endothelial cells.

References

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Further reading