Multiple organ dysfunction syndrome

  (Redirected from Multi-organ failure)

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

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

Although Irwin-Rippe cautions 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.


The condition usually results from infection, injury (accident, surgery), hypoperfusion and hypermetabolism. The primary cause triggers an uncontrolled inflammatory response. 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. However, in one-third of the patients 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. 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. However, they are essential components of a normal healthy immune response, so there is risk of decreasing vulnerability to infection, which can also cause clinical deterioration.


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 hypothesisEdit

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 hypothesisEdit

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 hypothesisEdit

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

Mitochondrial DNA hypothesisEdit

According to findings of Professor Zsolt Balogh and his team at 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 that survived major trauma.

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).

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

Integrated hypothesisEdit

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


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:


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]


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]


Mortality varies from 30% to 100% where the chance of survival is diminished as the number of organs involved increases. Since the 1980s the mortality rate has not changed.[1][dubious ] 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.[6]


The historical origin of the concept of MODS is as follows. 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]


  1. ^ a b c d e f g h i j k l Irwin & Rippe. Intensive Care Medicine. Archived from the original on November 7, 2005.
  2. ^ Matsuda N, Hattori Y (2006). "Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy". J. Pharmacol. Sci. 101 (3): 189–98. doi:10.1254/jphs.CRJ06010X. PMID 16823257.
  3. ^ Deitch EA. Simple intestinal obstruction causes bacterial translocation in man. Arch Surg 1989; 124: 699-701. PMID 2730322
  4. ^ McIlroy DJ; et al. (2014). "Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery". Journal of Critical Care. 29 (6): 1133.e1–5. doi:10.1016/j.jcrc.2014.07.013. PMID 25128442.
  5. ^ "MULTIPLE ORGAN FAILURE". ABC Australia. 7 August 2014.
  6. ^ Zeng, Ling; et al. (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 (6): 6. doi:10.1186/s13054-014-0727-2. PMC 4310192. PMID 25572180.

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