Multiple organ dysfunction syndrome is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis. Although Irwin-Rippe cautions in 2005 that the use of "multiple organ failure" or "multisystem organ failure" should be avoided, both Harrison's and Cecil's 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.
Cause
The condition usually results from infection, injury, 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. 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. 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 factorsNF-κB and AP-1 would be appropriate targets in preventing sepsis and SIRS. These two genes are pro-inflammatory. However, they are essential components of a normal healthy immune response, so there is risk of increasing vulnerability to infection, which can also cause clinical deterioration.
The most popular hypothesis by Deitch to explain MODS in critically ill patients is the gut hypothesis. 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.
Endotoxin macrophage hypothesis
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, interleukin-1, interleukin-6, thromboxane A2, prostacyclin, platelet activating factor, and nitric oxide.
Tissue hypoxia-microvascular hypothesis
As a result of macro- and microvascular changes insufficient supply of oxygen occurs. Hypoxemia causes cell death and organ dysfunction.
According to findings of Professor Zsolt Balogh and his team at University of Newcastle, 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. This results in catastrophic immune response leading to multiple organ dysfunction syndrome.
Integrated hypothesis
Since in most cases no primary cause is found, the condition could be part of a compromised homeostasis involving the previous mechanisms.
Diagnosis
The European Society of Intensive Care organized a consensus meeting in 1994 to create the "Sepsis-Related Organ Failure Assessment " 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. Four clinical phases have been suggested:
Stage 1 the patient has increased volume requirements and mild respiratory alkalosis which is accompanied by oliguria, hyperglycemia and increased insulin requirements.
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.
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,- 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.
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.
