Multiple organ dysfunction syndrome
856149
224732116
2008-07-10T04:36:31Z
Leonard^Bloom
5620165
Reverted edits by [[Special:Contributions/71.182.120.9|71.182.120.9]] to last version by DOI bot (using [[WP:HG|Huggle]])
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ICD9 = {{ICD9|995.92}} |
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eMedicineSubj = med |
eMedicineTopic = 3372 |
MeshID = D009102 |
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'''Multiple organ dysfunction syndrome''' '''(MODS)''', previously known as '''multiple organ failure (MOF)''', is altered [[organ (anatomy)|organ]] function in an acutely ill patient requiring [[medicine|medical]] intervention to achieve [[homeostasis]]. The use of "multiple organ failure" should be avoided since that term was based upon physiologic parameters to determine whether or not a particular organ was failing.<ref name="Irwin-Rippe">[http://www.lww.com/product/?0-7817-3548-3 Intensive Care Medicine] by Irwin and Rippe</ref>
==Origin==
Originally patients were classified as having ''[[sepsis]]'' or the ''sepsis syndrome''. This resulted in two concepts: the [[systemic inflammatory response syndrome]] (SIRS) and multiple organ dysfunction syndrome (MODS).<ref name="Irwin-Rippe"/>
==Definition==
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.<ref name="Irwin-Rippe"/>
==Etiology==
The condition usually results from infection, injury (accident, surgery), hypoperfusion and hypermetabolism. The primary cause triggers an uncontrolled [[inflammation|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.<ref name="Irwin-Rippe"/>
[[Multiple organ dysfunction syndrome]] is well established as the final stage of a continuum [[Systemic inflammatory response syndrome]] -> [[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]]. <ref> {{cite journal |author=Matsuda N, Hattori Y |title=Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy |journal=J. Pharmacol. Sci. |volume=101 |issue=3 |pages=189–98 |year=2006 |pmid=16823257 |doi=10.1254/jphs.CRJ06010X}}</ref> 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). <ref>{{cite journal |author=Kabay B, Kocaefe C, Baykal A, ''et al'' |title=Interleukin-10 gene transfer: prevention of multiple organ injury in a murine cecal ligation and puncture model of sepsis |journal=World J Surg |volume=31 |issue=1 |pages=105–15 |year=2007 |pmid=17171483 |doi=10.1007/s00268-006-0066-9}}</ref> 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.
==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 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)<ref name="Irwin-Rippe"/>
===Gut hypothesis===
The most popular theory 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.<ref name="Irwin-Rippe"/>
===Endotoxin macrophage theory===
[[Gram-negative]] infections in MODS patients are relatively common, hence [[endotoxin]]s have been advanced as principal mediator in this disorder. It is thought that following the initial event [[cytokine]]s 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]].<ref name="Irwin-Rippe"/>
===Tissue hypoxia-microvascular hypothesis===
As a result of macro- and microvascular changes insufficient supply of oxygen occurs. [[Hypoxia (medical)|Hypoxemia]] causes organ dysfunction and cell death.<ref name="Irwin-Rippe"/>
===Integrated hypothesis===
Since in most cases no primary cause is found, the condition could be part of a compromised homeostasis involving the previous mechanisms.<ref name="Irwin-Rippe"/>
==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.<ref name="Irwin-Rippe"/>
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]], [[hypocapnia|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.
==Management==
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. <ref name="Irwin-Rippe"/>
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]]<ref name="pmid12712239">{{cite journal |author=Dhainaut JF, Laterre PF, Janes JM, ''et al'' |title=Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial |journal=Intensive Care Med |volume=29 |issue=6 |pages=894–903 |year=2003 |pmid=12712239 |doi=10.1007/s00134-003-1731-1}}</ref>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 ([[number needed to treat]] = 13.5). [http://medinformatics.uthscsa.edu/calculator/calc.shtml?calc_rx_rates.shtml?eer=26.5&cer=33.9 Click here] to adjust these results for patients at higher or lower risk of 28-day mortality.
==Prognosis==
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.<ref name="Irwin-Rippe"/>
==See also==
*[[Acute renal failure]]
*[[Acute respiratory distress syndrome]]
*[[Heart failure]]
*[[Intensive care]]
*[[Liver failure]]
*[[Respiratory insufficiency]]
*[[Shock (medical)|Shock]]
*[[systemic inflammatory response syndrome]]
==References==
{{reflist}}
==Sources==
*[http://www.lww.com/product/?0-7817-3548-3 Intensive Care Medicine by Irwin and Rippe]
*[http://www.lww.com/product/?0-683-05565-8 The ICU Book by Marino]
*[http://www.cecilmedicine.com/buy.cfm?book=goldman Cecil Textbook of Medicine]
*[http://www.oup.com/us/catalog/general/subject/Medicine/PrimaryCare/?ci=0192629220&view=usa The Oxford Textbook of Medicine]
*[http://books.mcgraw-hill.com/medical/harrisons/ Harrison's Principles of Internal Medicine]
[[Category:Intensive care medicine]]
[[Category:Organ failure| ]]
[[Category:Causes of death]]
[[de:Multiorganversagen]]
[[pl:Niewydolność wielonarządowa]]
[[pt:Síndrome de disfunção múltipla de órgãos]]
[[vi:Hội chứng rối loạn chức năng đa cơ quan]]
[[zh:器官衰竭]]