Multiple organ dysfunction syndrome

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Multiple organ dysfunction syndrome
Other namesTotal organ failure, multisystem organ failure, multiple organ failure
Symptoms Include, but not limited to: confusion, loss of appetite, fatigue, fever, irregular heartbeat, tachypnea
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 immediate medical intervention. [1]

Contents

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

Multiple organ dysfunction syndrome can trigger a variety of symptoms throughout the body. Because MODS can impact any organ system, the specific symptoms experienced will depend on which organs are affected. Initially, these signs may be mild as the underlying illness progresses towards MODS. However, as the condition worsens, the symptoms can become more severe. [2]

These symptoms include low urine output, nausea, vomiting, and loss of appetite. Some patients experience mental symptoms like confusion and may feel fatigued. Symptoms like fever, chills, irregular heartbeat, and quick/shallow breathing are also common. Multiple cases of MODS also suffer chest and abdominal pain, and patients may even lose consciousness. [3]

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. [4] 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. [5] 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. [6] [7]

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 ]

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. [8] [9] [10] [11] [12]

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. [13]

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]

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.

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. The five cardinal signs are heat, pain, redness, swelling, and loss of function.

<span class="mw-page-title-main">Peritonitis</span> Inflammation of the inner wall of the abdomen (peritoneum)

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 response to 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">Lipopolysaccharide</span> Class of molecules found in the outer membrane of gram-negative bacteria

Lipopolysaccharide, now more commonly known as endotoxin, is a collective term for components of the outermost membrane of cell envelope of gram-negative bacteria, such as E. coli and Salmonella with a common structural architecture. Lipopolysaccharides (LPS) are large molecules consisting of three parts: an outer core polysaccharide termed the O-antigen, an inner core oligosaccharide and Lipid A, all covalently linked. In current terminology, the term endotoxin is often used synonymously with LPS, although there are a few endotoxins that are not related to LPS, such as the so-called delta endotoxin proteins produced by Bacillus thuringiensis.

<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">Acute respiratory distress syndrome</span> Respiratory failure due to widespread inflammation in the lungs

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common.

<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. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.

<span class="mw-page-title-main">Systemic inflammatory response syndrome</span> Inflammation affecting the whole body

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

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<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">Hypoalbuminemia</span> Abnormally low levels of albumin in the blood

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.

Felty's syndrome (FS), also called Felty syndrome, is a rare autoimmune disease characterized by the triad of rheumatoid arthritis, enlargement of the spleen and low neutrophil count. The condition is more common in those aged 50–70 years, specifically more prevalent in females than males, and more so in Caucasians than those of African descent. It is a deforming disease that causes many complications for the individual.

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<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.

Autoinflammatory diseases (AIDs) are a group of rare disorders caused by dysfunction of the innate immune system. These responses are characterized by periodic or chronic systemic inflammation, usually without the involvement of adaptive immunity.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 Irwin, Richard S.; Rippe, James M. (2003). Irwin and Rippe's Intensive Care Medicine. Lippincott Williams & Wilkins. ISBN   978-0-7817-3548-3.[ page needed ]
  2. ↑ "Multiple Organ Dysfunction Syndrome". Cleveland Clinic. 20 November 2023. Retrieved 7 July 2024.
  3. ↑ "Shock: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2024-07-07.
  4. ↑ Matsuda, Naoyuki; Hattori, Yuichi (2006). "Systemic Inflammatory Response Syndrome (SIRS): Molecular Pathophysiology and Gene Therapy". Journal of Pharmacological Sciences. 101 (3): 189–198. doi: 10.1254/jphs.crj06010x . PMID   16823257.
  5. ↑ Deitch, Edwin A. (1 June 1989). "Simple Intestinal Obstruction Causes Bacterial Translocation in Man". Archives of Surgery. 124 (6): 699–701. doi:10.1001/archsurg.1989.01410060065013. PMID   2730322.
  6. ↑ McIlroy, Daniel J.; Jarnicki, Andrew G.; Au, Gough G.; Lott, Natalie; Smith, Doug W.; Hansbro, Philip M.; Balogh, Zsolt J. (December 2014). "Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery". Journal of Critical Care. 29 (6): 1133.e1–1133.e5. doi: 10.1016/j.jcrc.2014.07.013 . hdl: 10453/146723 . PMID   25128442.
  7. ↑ "MULTIPLE ORGAN FAILURE". ABC Australia. 7 August 2014.
  8. ↑ Watson, R. Scott; Crow, Sheri S.; Hartman, Mary E.; Lacroix, Jacques; Odetola, Folafoluwa O. (2017). "Epidemiology and outcomes of pediatric multiple organ dysfunction syndrome (MODS)". Pediatric Critical Care Medicine. 18 (3 Suppl 1): S4–S16. doi:10.1097/PCC.0000000000001047. PMC   5334773 . PMID   28248829.
  9. ↑ van Wessem, Karlijn J.P.; Leenen, Luke P.H. (1 January 2018). "Reduction in Mortality Rates of Postinjury Multiple Organ Dysfunction Syndrome: A Shifting Paradigm? A Prospective Population-Based Cohort Study". Shock: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches. 49 (1): 33–38. doi:10.1097/SHK.0000000000000938. PMID   28682941. S2CID   206062912.
  10. ↑ Liu, Xiaoli; Hu, Pan; Mao, Zhi; Kuo, Po-Chih; Li, Peiyao; Liu, Chao; Hu, Jie; Li, Deyu; Cao, Desen; Mark, Roger G.; Celi, Leo Anthony; Zhang, Zhengbo; Zhou, Feihu (28 January 2020). "Interpretable Machine Learning Model for Early Prediction of Mortality in Elderly Patients with Multiple Organ Dysfunction Syndrome (MODS): a Multicenter Retrospective Study and Cross Validation". arXiv: 2001.10977 .{{cite journal}}: Cite journal requires |journal= (help)
  11. ↑ van Breugel, Johanna M. M.; Niemeyer, Menco J. S.; Houwert, Roderick M.; Groenwold, Rolf H. H.; Leenen, Luke P. H.; van Wessem, Karlijn J. P. (December 2020). "Global changes in mortality rates in polytrauma patients admitted to the ICU—a systematic review". World Journal of Emergency Surgery. 15 (1): 55. doi: 10.1186/s13017-020-00330-3 . PMC   7526208 . PMID   32998744.
  12. ↑ Sapan, Heber Bombang; Paturusi, Idrus; Jusuf, Irawan; Patellongi, Ilhamjaya; Massi, Muh Nasrum; Pusponegoro, Aryono Djuned; Arief, Syafrie Kamsul; Labeda, Ibrahim; Islam, Andi Asadul; Rendy, Leo; Hatta, Mochammad (1 June 2016). "Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma". International Journal of Burns and Trauma. 6 (2): 37–43. PMC   4913232 . PMID   27335696.
  13. ↑ Zeng, Ling; Du, Juan; Gu, Wei; Zhang, An-qiang; Wang, Hai-yan; Wen, Da-lin; Qiu, Lin; Yang, Xue-tao; Sun, Jian-hui; Zhang, Mao; Hao, Jiang; Jiang, Jian-xin (2015). "Rs1800625 in the receptor for advanced glycation end products gene predisposes to sepsis and multiple organ dysfunction syndrome in patients with major trauma". Critical Care. 19 (1): 6. doi: 10.1186/s13054-014-0727-2 . PMC   4310192 . PMID   25572180.

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