MODS severity determines mortality [5]. Organ failure severity scoring was initially described by Knaus in 1985 [6]. Modern scoring systems consider grade and severity and are intended to serve as predictors of outcome. Among the most commonly used scoring systems are the multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) and logistic organ dysfunction score (LODS) [7,8,9]. All include clinical and laboratory data for six organs: respiratory, cardiovascular, hematologic, hepatic, renal, and central nervous system (Table 160.1) [10]. The Denver Multiple Organ Failure (MOF) score is a simpler 4-point scale that has similar or superior specificity [11]. A “cellular injury score” based on measures of cellular dysfunction has also been described [12]. No single scoring system has been proven superior but all predict outcome more accurately than health care resource utilization [11,13]. The acute physiology and chronic health evaluation (APACHE), originally described by Knaus in 1985, is a scoring system that considers patient factors unrelated to the acute illness as well as acute illness severity [14]. APACHE considers many variables and is therefore not as easily calculable at
the bedside as MODS, SOFA, LODS, or Denver, but it reliably predicts both outcome and resource utilization, has been refined to its current version, APACHE IV, and may be useful for benchmarking ICU performance [15].

Incidence of MODS varies based on primary diagnosis and the scoring system used to determine organ dysfunction. Seventy-one percent of ICU patients have some organ dysfunction [16] and about half have MODS [17], depending on the criteria used. For example, in one adult trauma ICU 47% had MODS, defined by SOFA ≤ 3 in two or more systems [18]. Septic patients are more likely to have organ dysfunction and more organ failures than nonseptic patients and mortality is higher if sepsis is present (31% vs. 21%) [16].

MODS is most often the result of shock, sepsis, and trauma but there are many causes (Table 160.2) [19]. Forty-one percent of those patients with organ dysfunction have sepsis [16]. Sepsis most commonly originates in the lung (68%) and abdomen (22%) but there are many causes of sepsis-induced MODS [16].

The systemic inflammatory response syndrome (SIRS) is frequently viewed as a predecessor to MODS and these syndromes represent a continuum of dysfunction. Components of the SIRS response are seen in virtually all patients following operation or injury. This response is usually self-regulating and rarely progresses to MODS. MODS may be viewed as a result of an ongoing and dysregulated SIRS response with progressive organ system derangement.

Despite extensive efforts, the pathophysiology of MODS is not fully understood and remains an area of intensive investigation [20]. Several mechanisms for the onset and propagation of MODS have been proposed, including an initial insult leading immediately to organ failure, a “two hit” model, where an initial stimulus primes the immune system to respond to a subsequent insult with an exuberant reaction, and the concept that a continuous ongoing insult contributes to MODS [20]. In clinical practice, each of these scenarios may result in MODS.

A common theme in the onset and propagation of MODS is the presence of a disordered immune response. It is likely that ongoing tissue hypoxia leads to activation of the acute inflammatory response and to dysregulation of the immune system [21]. Although the inflammatory response is an important component of normal recovery from injury and illness, organ failure appears to result from a loss of the balance between the pro- and anti-inflammatory cascades [22]. The proinflammatory response to a stimulus predominates initially, with increased release of proinflammatory mediators, increased capillary permeability, macrophage and neutrophil activation with tissue invasion and damage, disordered apoptosis, and microvascular thrombosis [23]. This initial response is normally tempered by the anti-inflammatory response, but this relationship may become dysfunctional. Together, these processes lead to early onset of MODS. If the organism survives the initial insult and onset of MODS, a period of immunosuppression follows. During this period, the patient becomes highly susceptible to nosocomial infection, with a normally survivable event such as pneumonia representing a life-threatening “second hit” [24].