- Multiple organ dysfunction syndrome
Multiple organ dysfunction syndrome Classification and external resources ICD-9 995.92 eMedicine med/3372 MeSH D009102
Multiple organ dysfunction syndrome (MODS), previously known as multiple organ failure (MOF) or multisystem organ failure (MSOF), is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis. The use of "multiple organ failure" or "multisystem organ failure" should be avoided since that term was based upon physiologic parameters to determine whether or not a particular organ was failing.
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 also been developed: the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS).
Multiple organ 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.
The condition usually results from infection, injury (accident, surgery), hypoperfusion and hypermetabolism. The primary cause triggers an uncontrolled inflammatory response. In operative and non-operative patients sepsis is the most common cause. Sepsis 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. Multiple organ dysfunction syndrome is well established as the final stage of a continuum Systemic inflammatory response syndrome + 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 Systemic inflammatory response syndrome. 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.
Some have developed a mouse model sepsis via cecal ligation and puncture (CLP). Male Balb/c mice subjected to CLP were given an IL-10-carrying vector or an empty control vector. Lung, Liver and kidney tissue destruction were measured by assessing myeloperoxidase and malonialdehyde activity. These last two are endogenous oxidizing compounds produced during tissue inflammation. The authors assessed the level neutrophil infiltration in lung and liver tissue. IL-10 protein expression was measured using immunohistochemistry. The expression of Tumor necrosis factor-alpha mRNA was measured at 3,8, and 24 hours after CLP using reverse transcription polymerase chain reaction. Their results show significantly reduced organ damage by IL-10 gene transfer, as quantified by reduced myeloperoxidase activity in the lung, liver, and kidney. The malonialdehyde level was not affected by the transfer into the liver. The livers of the mice infected with the adenoviral vector showed reduced neutrophil activity. The lung and kidney samples in mice carrying the gene showed lower expression of Tumor necrosis factor-alpha mRNA. The investigators concluded that increased IL-10 expression significantly reduced sepsis-induced Multiple organ injury.
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 after the original insult. Following this one might see hepatic failure (5–7 days), gastrointestinal bleeding (10–15 days), and renal failure (11–17 days)
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. Hepatic 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
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.
Tissue hypoxia-microvascular hypothesis
Since in most cases no primary cause is found, the condition could be part of a compromised homeostasis involving the previous mechanisms.
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.
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.
- Stage 2 the patient is tachypneic, hypocapnic and hypoxemic. Moderate liver dysfunction and possible hematologic abnormalities.
- Stage 3 the patient develops shock with azotemia and acid-base disturbances. Significant coagulation abnormalities.
- Stage 4 the patient is vasopressor dependent and oliguric or anuric. Ischemic colitis and lactic acidosis follow.
At present there is no agent that can reverse the established organ failure. Therapy therefore is 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.
Human recombinant activated protein C(activated drotrecogin alfa) can reduce 28-day mortality among patients with multiple organ dysfunction syndrome according to a randomized controlled trial. The relative risk reduction was 21.8%. For patients at similar risk to those in this study (33.9% had 28-day mortality), this leads to an absolute risk reduction of 7.4%. 13.5 patients must be treated for one to benefit.
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.
- Acute renal failure
- Acute respiratory distress syndrome
- Heart failure
- Intensive care
- Liver failure
- Respiratory insufficiency
- systemic inflammatory response syndrome
- ^ a b c d e f g h i j k l Intensive Care Medicine by Irwin and Rippe
- ^ 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.
- ^ Kabay B, Kocaefe C, Baykal A, et al. (2007). "Interleukin-10 gene transfer: prevention of multiple organ injury in a murine cecal ligation and puncture model of sepsis". World J Surg 31 (1): 105–15. doi:10.1007/s00268-006-0066-9. PMID 17171483.
- ^ Deitch EA. Simple intestinal obstruction causes bacterial translocation in man. Arch Surg 1989; 124: 699-701.
- ^ Dhainaut JF, Laterre PF, Janes JM, et al. (2003). "Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial". Intensive Care Med 29 (6): 894–903. doi:10.1007/s00134-003-1731-1. PMID 12712239.
- The ICU Book by Marino
- Cecil Textbook of Medicine
- The Oxford Textbook of Medicine
- Harrison's Principles of Internal Medicine
Health science · Medicine · Medical specialities · Intensive care medicine / Critical care medicine and Respiratory therapy General terms ConditionsOrgan system failureComplications Diagnosis Life supporting treatments Drugs ICU scoring systems Organisations Related specialties Organ failure General MultipleMultiple organ dysfunction syndrome
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