Critical Care Clinics

Volume 16 • Number 2 • April 2000
Copyright © 2000 W. B. Saunders Company


Robert A. Balk MD
-------------------------------------------------------------------------------Department of Internal Medicine, Section of Pulmonary and Critical Care Medicine, Rush
Medical College and Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois
-------------------------------------------------------------------------------Address reprint requests to
Robert A. Balk, MD
Section of Pulmonary and Critical Care Medicine
Rush-Presbyterian-St. Luke's Medical Center
1753 West Congress Parkway
Chicago, IL 60612

Improvements in initial resuscitation efforts coupled with advancements in technological
support and knowledge of disease process have improved the survival of critically ill patients
and resulted in a relatively new disorder, multiple organ dysfunction/failure. [2] [6] [13]
These advances in supportive care coupled with longer survival time allow the critically ill
patient to develop later stages of their illness and become susceptible to the common
complications of critical illness. [6] In prior years, patients would have died much earlier in
their disease course, long before they would develop the evidence of organ dysfunction that
we now refer to as multiple organ dysfunction syndrome (MODS) or multiple organ failure
(MOF). The initial reports of MOF were in 1969. [13] It was evident that survival was
dependent on factors other than the initial disease process for which the patient was
admitted. Multiple organ dysfunction/failure is now regarded as the most common cause of
death among patients in the noncoronary critical care unit and also is a frequent cause of
morbidity, prolonged hospitalization, and increased cost of care. [2]

Unfortunately, there is not a uniformly accepted definition for MODS/MOF. [42] In addition,
there is no agreement as to the exact definition of specific organ system dysfunction or
failure. More importantly there are no data to guide the clinician in ascertaining when organ
dysfunction is reversible or when it is irreversible. In an attempt to eliminate some of the
confusion and to bring a degree of uniformity to the definitions for MODS/MOF, a Consensus
Conference was held by the American College of Chest Physicians (ACCP) and the Society of
Critical Care Medicine (SCCM). [45] The consensus conference put forward an operational

2. or > 10% immature (band) forms. Hypoperfusion and perfusion abnormalities may include. Patients receiving inotropic or vasopressor agents may no longer be hypotensive by the time they manifest hypoperfusion abnormalities or organ dysfunction. ACCP/SCCM Consensus Conference Definitions Systemic Inflammatory Response Syndrome (SIRS) The systemic inflammatory response to a wide variety of severe clinical insults. 2. or an acute alteration in mental status. .000/mm3 . • Severe Sepsis/SIRS. 4. Presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention. The clinical manifestations would include two or more of the following conditions as a result of a documented infection: 1. [45] MODS was defined as the presence of altered organ function in an acutely ill patient such that homeostasis could not be maintained without intervention. It should be determined whether they are a direct systemic response to the presence of an infectious process and represent an acute alteration from baseline in the absence of other known causes for such abnormalities.definition for multiple organ failure/dysfunction and proposed the acronym MODS for the multiple organ dysfunction syndrome. • • Multiple Organ Dysfunction Syndrome (MODS). [45] The consensus statement also reaffirmed the belief that the dysfunction could be absolute or relative and recognized that there is a continuum of change from dysfunction to failure (see Display Box 1 ). hypoperfusion. or hypotension. 4. yet they would still be considered to have septic (SIRS) shock.000/mm3 . manifested by two or more of the following conditions: 1. Sepsis The systemic inflammatory response to infection. oliguria. < 4000/mm3 . Display Box 1. Septic Shock/SIRS Shock. manifestations of sepsis are the same as those previously defined for SIRS. but are not limited to. Box 1. Sepsis (SIRS) associated with organ dysfunction. Sepsis (SIRS) Induced Hypotension. A systolic blood pressure < 90 mm Hg or a reduction of 40 mm Hg from baseline in the absence of other causes for hypotension. 3. or an acute alteration in mental status. but are not limited to. In association with infection. Temperature > 38/C or < 36/C Heart rate > 90 beats/min Respiratory rate > 20 breaths/min or Pa CO2 < 32 mm Hg WBC count > 12. or > 10% immature (band) forms. lactic acidosis. Temperature > 38/C or < 36/C Heart rate > 90 beats/min Respiratory rate > 20 breaths/min or Pa CO2 < 32 mm Hg WBC count > 12. < 4000/mm3 . lactic acidosis. 3. oliguria. A subset of severe sepsis (SIRS) and defined as sepsis (SIRS) induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include.

Secondary MODS is the term used to describe the onset of organ dysfunction/failure that develops later in the course of illness and is frequently related to shock and sepsis. organ dysfunction is likely to ensue [10] . SIRS. MODS/MOF is currently recognized as a major cause of mortality in SIRS. Nonetheless. and exogenous mediators are listed below: Potential Mediators Involved in the Pathogenesis of MODS/MOF Potential Humoral Mediators • • • • • • • • • • • • • • Complement Products of Arachidonic Acid Metabolism Lipoxygenase products Cyclooxygenase products Tumor Necrosis Factor Interleukins (1-13) Growth Factors Adhesion Molecules Platelet Activating Factor Procoagulants Fibronectin and Opsonins Toxic Oxygen Free Radicals Endogenous Opioids-Endorphins Vasoactive Polypeptides and Amines . sepsis. [50] INCIDENCE AND EPIDEMIOLOGY Given the difficulties with accepted definitions. this uncertain incidence is related to lack of a uniformly accepted definition. such as hypotension and/or decreased cardiac output. it is not surprising that the actual incidence of MODS/MOF is unknown. bowel infarction. cellular. and alcohol abuse. [3] [20] [31] [33] [47] [51] [60] [61] Potential Mediators The frequent association of MODS/MOF with sepsis. this delicate balance is difficult to achieve and there is a predominance of either the inflammatory response or the anti-inflammatory response. the acute respiratory distress syndrome (ARDS). increased age. the patient is at risk for opportunistic or secondary infections. and other critical illnesses. There are a variety of potential mediators for the injury process seen in sepsis and other causes of SIRS. When there is an excessive inflammatory reaction. hepatic dysfunction. trauma. when there is an excessive anti-inflammatory response. [50] This condition has been termed primary MODS. which could result in organ dysfunction/failure. [10] [14] [19] [21] [22] [26] [30] [39] [41] [49] [50] [53] [59] A number of the potential humoral. which represents the body's attempt to limit the SIRS response so that it is not counterproductive. but there also is uncertainty concerning how to factor in pre-existing organ dysfunction/failure. [10] The subsequent balance between the proinflammatory (SIRS) and anti-inflammatory (CARS) response has been referred to as the mixed antagonistic response syndrome or MARS. and other inflammatory processes suggests that there may be a causal link to the complex pathophysiologic processes that are characteristic of SIRS. shock and prolonged periods of hypotension. [20] [22] [24] [37] [39] [43] [46] Recent evidence has suggested that the SIRS response is rapidly followed in most patients by a compensatory anti-inflammatory response syndrome (CARS). [10] Development of subsequent infections may serve as an additional insult to again trigger the SIRS response.It also was recognized that the initial injury may produce direct organ system injury or be accompanied by hemodynamic alterations. ARDS. [10] Typically. Major risk factors include sepsis and the systemic inflammatory response syndrome (SIRS). In part. trauma.

In addition. and it is likely that these pathways are operational in most patients who develop this complication of critical illness. The proponents of translocation of intestinal bacteria and/or endotoxin (see farther on). bradykinin and other kinins. fibronectin and opsonins. various growth factors. exotoxin. products of arachidonic acid metabolism (both lipoxygenase and cyclooxygenase metabolites). In some cases one mechanism may be instrumental early in the course of illness and subsequent organ function may be adversely affected through other pathways that accompany later inflammatory cascades or hits. [50] Further injury may ensue and be fueled by a variety of mediators and the interaction of multiple pathways. suggest that this is an extremely likely pathway for the development of MODS/MOF. This chain of event has led some to suggest that there may be multiple hits that eventually result in the development of MODS/MOF. procoagulants. interleukins 1 to 15 (IL 1-15). [12] Potential Pathophysiologic Mechanisms of Multiple Organ Dysfunction Syndrome/Multiple Organ Failure The exact pathophysiology of the development of MODS/MOF has not been completely defined. adhesion molecules. The impact of MODS/MOF on patient outcome. vasoactive polypeptides and amines. there may be exogenous mediators such as endotoxin. it is extremely probable that there are multiple pathways that result in the organ system dysfunction/damage. even without clinical or microbiologic evidence of infection with gram-negative organisms supports the potential role of translocation in the production of MODS/MOF. monocytes and macrophages. tumor necrosis factor (TNF). several of these pathways are likely to be operational in a given patient. and cost of care are enormous and support the vigorous attempts to define ways to prevent and treat organ system dysfunction/failure. Among the cellular inflammatory mediators are polymorphonuclear leukocytes (PMNLs). nitric oxide. platelet activating factor (PAF). platelets. and coagulation factors and their degradation products.• • • • Bradykinin and Other Kinins Neuroendocrine Factors Myocardial Depressant Factor Coagulation Factors and Their Degradation Products Cellular Inflammatory Mediators • Polymorphonuclear Leukocytes • Monocytes/Macrophages • Platelets • Endothelial Cells Exogenous Mediators • Endotoxin • Exotoxin and Other Toxins The humoral mediators include components of the complement system. and endothelial cells. In fact. it is likely that multiple . [5] [17] This hypothesis is supported by the demonstration of circulating levels of endotoxin in the peripheral blood of critically ill patients with sepsis and SIRS. toxic oxygen free radicals. Cellular inflammatory mediators also may be involved in the production of this injury state. [14] Reports of endotoxemia in these critically ill patients. [5] [17] [27] As previously mentioned. In the typical clinical setting. resource use. [6] [20] It is likely that there are multiple pathways that can result in the organ damage. endogenous opiods (endorphins). It is likely that no single mediator is the key to the production of MODS/MOF in all settings. neuroendocrine factors. myocardial depressant factor. and other toxins that may be instrumental in the production of organ or tissue injury. possibly as a result of intestinal ischemia or ischemia/reperfusion. The fact that there is no single pathway for organ system dysfunction/failure makes treatment extremely difficult and has generated the current enthusiasm toward defining methods of prevention.

[20] [22] [37] Pinsky et al [49] have termed this process "malignant intravascular inflammation". it may be a common manifestation of the SIRS response. which may obstruct the small capillaries and impair the delivery of blood and substrate to the tissues. PMNLs. and the resultant ischemic injury may contribute to other potential mechanisms of organ dysfunction/failure. called myocardial depressant factor. or a selective alteration in the perfusion of an individual organ system. and fibrin..e. myocardial depressant substance) Circulating immune/inflammatory mediators Protein calorie malnutrition Bacterial-toxin translocation Defective red blood cells Adverse effect of directed treatment or medication Primary cellular injury may result from the direct effect of the underlying disease process or from the direct toxicity of the systemically released mediators of the SIRS response. or a combination of these factors. [20] The vascular endothelial cell injury could then result in a permeability defect or compromise the integrity of the vascular endothelium. [20] [26] The ischemic or poorly perfused intestinal tract may have altered barrier function and give rise to translocation of intestinal bacteria and toxins. there may be an inability of the mitochondria or cells to take up or use the delivered oxygen and substrate. decreased systemic perfusion pressure. which may produce organ system dysfunction/failure. which may act individually or collectively in the production of organ system dysfunction. [20] [22] [41] [49] There may be inadequate tissue perfusion or the maldistribution of blood flow which contains oxygen. [29] Some authors have speculated that even though adequate blood flow may reach the various tissue beds. [20] [22] [37] [42] [43] [50] The maldistribution of perfusion may be the result of decreased delivery. which is frequently seen in the setting of sepsis and SIRS. RBCs. decreased oxygen uptake. [20] [50] These intravascular clots are similar to lesions described in experimental models of acute lung injury and sepsis and may represent a subclinical form of disseminated intravascular coagulation (DIC). [20] Tissue ischemia also may result from the microaggregation of microthrombi composed of platelets. Another hypothesis proposes the occurrence of diffuse endothelial cell injury from elaborated mediators of the SIRS response. which may further the injury state. there are a number of mechanisms that may produce an ischemic injury. leading to subsequent organ edema or compromise organ system function. [20] [48] [59] One such substance is the circulating depressant factor. [20] The period of ischemia may be followed by reperfusion and oxidative injury. are listed below. In the setting of sepsis and SIRS there is commonly a decrease in the cardiac output. which may result in hypoperfusion or ischemia of the organ system. it has been associated with the development of reversible biventricular failure in some patients with . nutrients. [5] [15] [25] [58] In summary. [11] [20] [22] [37] [39] [41] [53] This process has been proposed to explain the development of acute lung injury and the acute respiratory distress syndrome (ARDS). and other important substrates required to support cellular and organ function necessary to preserve the integrity of the cell or organ.pathophysiologic mechanisms and mediators may be involved in the pathogenesis of this injury process. impaired metabolism. such as TNF and other proinflammatory cytokines. Circulating humoral factors have been detected in some critically ill patients and may be responsible for the development of organ system dysfunction. A number of the potential pathophysiologic mechanisms. Potential Pathophysiologic Mechanism(s) Involved in the Production of MODS/MOF • • Primary cellular injury Inadequate tissue/organ perfusion Hypoperfusion Ischemia/Reperfusion Microaggregation and/or disseminated intravascular coagulation • • • • • • • Diffuse endothelial cell injury Circulating humoral factors (i.

septic shock. A frequent example is renal dysfunction that results from use of aminoglycosides. Malnutrition and intestinal ischemia are both known causes of bacterial-toxin translocation. central nervous system. [16] The clinician must be aware of these potential relationships. Recent data support the involvement of TNF and IL-1 as important contributors of myocardial depression. A large number of therapeutic agents and procedures have the potential to produce undesirable adverse effects on a variety of organ systems. thus. they may enter the systemic circulation or the portal circulation where they can trigger the systemic inflammatory response and produce or amplify MODS/MOF. [20] [41] In the presence of the activated coagulation system and endothelial abnormalities characteristic of the inflammatory state. These bacteria and their toxic products may then translocate through or between the dysfunctional intestinal mucosal barrier cells and enter the mesenteric lymph system. and the offending agents should be stopped or changed whenever possible as part of the management strategy. renal. and the cardiovascular system. gastrointestinal system. but there is no uniformity or consistency in their assessment of organ dysfunction. even though the stroke volume and the cardiac output may be adequately maintained or even increased. may be particularly at risk for the development of protein calorie malnutrition. Finally. This variability in the assessment of specific organ function has contributed to the confusion surrounding the terminology of MODS/MOF and to the imprecision with which this topic is addressed in clinical trials and written reports (see Display Box 2 ). [17] [20] [27] Recent reports have suggested that there are defective red blood cells with altered shapes or rheologic properties that may predispose to plugging or obstruction of the microvasculature and result in cellular or tissue ischemia. hepatic. [1] [3] The malnutrition may compromise the patient's immune function and the ability to mount an adequate inflammatory response against the offending agent. A number of scoring systems and descriptive tools have been used in clinical trials and descriptive reports. amphotericin. there is an increase in end-diastolic volume and a reduction in the ejection fraction. ASSESSMENT OF ORGAN FUNCTION To date. these altered red blood cells may further contribute to the perfusion abnormalities that may result in MODS/MOF. they likely function by causing an increase in NO formation through the inducible form of nitric oxide synthase. The terminal ileum and cecum are large reservoirs for gram-negative bacteria and their toxic products. . there has been no uniform acceptance of an assessment tool for abnormal organ function in patients with suspected MODS. or other nephrotoxic agents. [17] [20] [27] [58] If they are not adequately neutralized by the mesenteric lymph nodes. [36] [40] [42] [44] [52] [61] Most of the proposed tools use an assessment of seven major organ systems: respiratory. hematological system. [48] [59] In this setting. such as endotoxin. [1] [3] [17] It is hypothesized that a loss of the intestinal mucosal barrier function may result from ischemia or abnormal cell function related to mucosal cell death or injury. at least in experimental animal models of injury. critically ill patients may have organ dysfunction that may be the result of some of the treatments employed in the management of their illness. [35] [48] [59] Critically ill patients are frequently catabolic and.

Immune System Dysfunction may be indicated by development of hospital-acquired infections. use of inotropic or vasopressor support. confusion. Changes in heart rate. which may be reflected by a decreased Pa O2 /Fi O2 or the need for supplemental oxygen. Excessive bleeding and ecchymoses are also considered in some scoring systems as evidence of organ dysfunction. hypoalbuminemia. it may be necessary to use sophisticated imaging techniques and other diagnostic studies in addition to obtaining adequate culture specimens from potential infective sources. Common Clinical and Laboratory Methods to Evaluate Specific Organ System Dysfunction Respiratory Dysfunction has been described in a variety of ways. or other evidence of disseminated intravascular coagulation. such as Acute Physiology and Chronic Health Evaluation (APACHE) II. [40] [61] In other evaluation tools. Hypoalbuminemia and an elevated prothrombin time may also indicate hepatic dysfunction. the urine output (especially the presence of oliguria). or cardiac arrest are also considered to be evidence for cardiovascular dysfunction by some authors. acalculous cholecystitis. ileus. and the presence of a coagulopathy with an elevation of the prothrombin time. intestinal ischemia or infarction. A new concept of the pressure adjusted heart rate has recently been introduced and is represented by the ratio of the heart rate and mean arterial pressure. or as the need to use an organ support intervention. partial thromboplastin time. Early administration of appropriate. Hepatic Dysfunction may be reflected by the presence of jaundice or hyperbilirubinemia. lactate dehydrogenase. Some evaluation tools use aspects of severity of illness scoring systems. Hematologic Dysfunction system may be reflected by thrombocytopenia. Display Box 2. fibrin degradation products. the presence of arrhythmias. coma. elevated serum transaminases. or the need for renal replacement therapies (such as dialysis). and the development of a gastrointestinal perforation. Neurologic Dysfunction is primarily reflected by alterations in level of consciousness and cerebral function. Cardiovascular Dysfunction may be manifested as hypotension. obtundation. effective antibiotic therapy has been shown to be beneficial in the management . The level of positive end-expiratory pressure (PEEP) and/or the use of mechanical ventilatory support may also be used to define respiratory dysfunction. or alkaline phosphatase. such as renal replacement therapy or mechanical ventilatory support (see the article by Vincent et al elsewhere in this issue). and psychosis. and elevated central venous pressure or pulmonary capillary wedge pressure. pancreatitis. Gastrointestinal Dysfunction may be manifest as gastrointestinal bleeding. The specific treatment is directed at identifying and treating the underlying disorder. the intolerance of enteral nutritional support. Manifestations of endocrine dysfunction would include hyperglycemia from insulin resistance. The duration of the mechanical ventilatory support or the use of nonconventional ventilatory support strategies may be used to distinguish the severity of the respiratory abnormality. organ dysfunction is described according to the presence of a single physiologic or biochemical abnormality. and it is imperative to investigate diligently for the presence of active infection. pyrexia. MANAGEMENT OF MODS/MOF The current management of patients with MODS/MOF is predominantly supportive.Box 2. weight loss. Renal Dysfunction may be reflected by the serum creatinine. Among the most common is the presence of altered oxygenation status. Endocrine Dysfunction is less commonly included in the organ assessments. leukocytosis or leukopenia. Frequently. increased leukocytosis. Evidence of altered CNS function includes decreases in the Glascow Coma Score. and hypercatabolism. Infection and sepsis are common predisposing conditions for the development of MODS/MOF. hypertriglyceridemia. and alterations in immune activity.

The initial agent should be fluid to ensure that the circulating intravascular volume is appropriate. Affected patients also are subject to all of the potential complications that may befall the critically ill. There is controversy as to which type of fluid is preferable. [55] Tissue oxygen delivery can be increased using inotropic agents to increase the cardiac output or by increasing the hemoglobin with red blood cell transfusions to increase the oxygen carrying capacity of the blood. [12] [55] The use of inotropic and vasoactive agents may be associated with the development of arrhythmias and even ischemia of some selected organ beds. and microcirculatory dysfunction. randomized. because this relationship was predominantly evident when the oxygen delivery and the oxygen consumption were calculated using standard formulae. The decision regarding early intubation and ventilatory support needs to be weighed against the potential complications associated with the procedure and the inability of the patients to protect their own airways. Emphasis should be placed on prevention of MODS/MOF in the critically ill patient because its onset has a dramatic effect on morbidity and mortality. as a means to maintain the integrity of the intestinal mucosal barrier function and decrease the likelihood of bacterial or toxin translocation has recently been emphasized. [27] Enteral nutrition also supports the integrity of the upper gastrointestinal tract and may obviate the need for other agents that are used to prevent stress-related gastrointestinal bleeding. Pulmonary management is directed at supporting oxygenation and ventilation. which include transmission of infectious agents. prospective. [34] Potential toxicity has been demonstrated in some patients who were subjected to strategies designed to greatly increase oxygen delivery by inotropic support of the cardiac output. In blood that has been stored for longer than 15 days in citrate phosphate dextrose adenine 1 (CPDA-1) there may be a loss of normal red blood cell deformability with a potential for microcirculatory dysfunction. controlled trial failed to demonstrate improved survival using a therapeutic strategy designed to increase the tissue oxygen delivery to supranormal levels. A persistently low gastrointestinal intramucosal pH (pHi) and serum lactate concentration have been shown to be associated with increased mortality and the development of MODS/MOF. the definition of adequate has been a topic of debate and controversy. and volume expanders is beyond the scope of this article. Past studies performed primarily in a surgical population demonstrated an improved survival in those patients who were managed with strategies to increase tissue oxygen delivery. Recent studies suggest that this previously demonstrated oxygen supply dependence may actually reflect mathematical coupling. Other potential approaches to prevent stress-related gastrointestinal bleeding include the use of histamine type 2 blockers and cytoprotective agents. [32] It is important to restore and maintain hemodynamic stability. The value of early intubation and mechanical ventilatory support to reduce the blood flow to the diaphragm and accessory muscles of respiration has been advocated by some clinicians. There is no disagreement on the importance of ensuring an adequate amount of tissue oxygen delivery. effective drainage or surgical debridement should be used. [12] [32] [34] Whether there is an oxygen supply dependency in the setting of critical illness has been debated and may depend on individual patient factors and the methods used to quantify the oxygen use. Supportive measures for the patient with MODS/MOF include those basic management provisions that are essential for all critically ill patients. [50] When necessary.of infected patients. Unfortunately. [34] The use of packed red blood cell transfusions to increase the oxygen carrying capacity of blood needs to be counterbalanced by the potential risks. vasoactive medications should be used to improve hemodynamic function and ensure adequate oxygen delivery to the tissues. [25] The importance of early nutritional support. colloid. blood products. predominantly using the enteral route. Strategies to prevent deep vein . If the use of appropriate type and volume of fluid does not adequately resuscitate the patient. immune suppression. [32] [34] A large. and a discussion of the pros and cons of crystalloid. but supporting data from human studies are lacking. Some centers advocate the use of gastrointestinal tonometry to assess the adequacy of mesenteric blood flow and intestinal perfusion.

randomized. and tissue factor pathway inhibitor infusions. placebo-controlled trials. neutralizing. prospective. These disorders may explain prolonged ventilator dependency in some critically ill patients and may necessitate rehabilitation efforts even after weaning or separation from ventilatory support before the patients are able to return home and care for themselves. Studies are ongoing in an attempt to define the role. in surgical patients who have increased risk for the development of MODS/MOF. none of these approaches has been demonstrated in multicenter. attention has turned toward the development of strategies to prevent the development of MODS/MOF. Clinical investigations have undertaken innovative trials aimed at blocking. The true benefit of this technique remains to be established. which are currently underway. [11] It may take up to 3 to 6 months for the axons to sufficiently recover. also demonstrated increased resolution of established organ dysfunction in the initial trials. which couples topical and systemic antimicrobial therapy in an attempt to decrease the development of nosocomial infections and the complications associated with their development. randomized.thrombosis and pulmonary emboli should be used unless there are specific contraindications. 1998). if any. of antimediator therapy in the management of patients with MODS/MOF. [23] Antithrombin III has been shown to improve the oxygenation index (Pa O2 /Fi O2 ratio) in critically ill patients who were found to have less than 70% antithrombin III activity at baseline. [2] The onset of organ dysfunction has been heralded as a bad prognostic sign and has been referred to as the major cause of death in most noncoronary . The beneficial value of this therapeutic approach awaits the completion of prospective. Data have demonstrated prevention of acute respiratory distress syndrome using the thromboxane synthetase inhibitor. controlled trials to be effective in preventing or treating MODS/MOF in the critically ill patient. or removing the potential inflammatory mediators and at designing support strategies using increased tissue oxygen delivery. Prevention has been investigated using the expensive technique of selective digestive decontamination. [11] The pathophysiology of critical illness polyneuropathy involves primary axonal degeneration that likely results from proinflammatory mediators. ketoconazole. PREVENTION OF MODS/MOF Given that there is no specific therapeutic treatment. PROGNOSIS The development of MODS/MOF in a critically ill patient has been associated with a high risk for morbidity and mortality. The development of neuromuscular weakness recently has been recognized as a potential complication in this group of patients and has been termed critical illness polyneuropathy or polymyopathy. a subsequent confirmatory trial failed to find a statistical benefit to this form of treatment (Derek Angus. however. recent concern has emerged related to the potential for this technique to remove the inflammatory as well as the anti-inflammatory mediators. personal communication. Some centers are investigating the use of continuous venovenous hemofiltration as a means of removing circulating inflammatory mediators [18] . activated protein C. MD. E-5. however. Early trials of antiendotoxin therapy with the human and murine monoclonal antibodies against endotoxin demonstrated a decrease in development of multiple organ dysfunction. [38] Eisele et al [23] analyzed several studies of critically ill patients with sepsis or after trauma and reported that there was less organ dysfunction in the patients who had received antithrombin III infusions compared with those treated with placebo. [56] The activation of the coagulation system and the potential of microthrombi to obstruct the blood flow to vital tissues is currently under evaluation using antithrombin III. [8] The murine monoclonal antibody. [8] [9] [12] [18] [28] [32] [62] Unfortunately up to this point.

As demonstrated in Figure 1 (Figure Not Available) . Cook DJ. and kidney. et al: Multiple Organ Dysfunction Score: A reliable descriptor of a complex clinical outcome. liver.intensive care units. we must focus our attention primarily on prevention. Figure 1. 1995. there is an increase in mortality as the MODS score increases. [9] [16] [54] [57] Specific scoring systems have been used to quantify the level of organ dysfunction and have been primarily used in the evaluation of various investigational agents. It is hoped that in the near future we will have specific forms of therapy in our clinical armamentarium to allow for improved outcomes in these critically ill patients. lung. Crit Care Med 23:1638-1652. [43] Until we have the ability to provide specific therapy for the treatment of organ dysfunction/failure.) . with permission. [2] The risk for death increases with the number of organ systems failing and the duration of the failure. [39] Studies also have demonstrated that there is a higher risk of mortality associated with some specific organ systems when they become dysfunctional or fail. (Figure Not Available) Aggregate multiple organ dysfunction score and mortality. ( From Marshall JC. Included in the list of organs with a high rate of mortality when they fail are the brain. Christou NV. rather than just support. The use of a MODS score has been proposed as a prognostic index.