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The multiple organ failure syndrome (MOF) is a relatively new entity defined as the successive occurrence of respiratory (ARDS), hepatic, renal, myocardial, gastro-intestinal or neurological failure in patients with hyperkinetic haemodynamic and hypermetabolic states. The etiologies are: infection, septic and non-septic shock, burns and multiple injuries. The MOF syndrome is considered to be a generalised "inflammatory reaction" to tissue aggression involving a cascade of mediatory factors (TNF, interleukines...) of macrophagic, lymphocytic origin, causing multiple organ failure. The treatment depends on early correction of cellular hypoxia related to circulatory disturbances, nutritional support, anti-infective therapy and, in the near future, "control of mediator activity" (immunotherapy).
Twenty-nine patients with acute renal failure and multiple organ failure were treated with continuous arterio-venous or veno-venous haemofiltration for a period of 6 +/- 5 days. Sixteen of these patients were improved and haemofiltration was withdrawn, but secondary worsening occurred in 8 cases. The method is well tolerated by the cardiovascular system and provides a satisfactory metabolic control. The low patient's survival rate (27 percent) is due to the severity of the disease. In the absence of controlled studies, it is difficult to assert that continuous haemofiltration is better than conventional haemodialysis.
Multiple alterations in inflammatory and immunologic function have been demonstrated in clinical and experimental situations after trauma and hemorrhage, in particular the activation of various humoral (e.g. complement, coagulation) and cellular systems (neutrophils, endothelial cells, macrophages). As a consequence of this activation process there is synthesis, expression and release of numerous mediators (toxic oxygen species, proteolytic enzymes, adherence molecules, cytokines), which may produce a generalized inflammation and tissue damage in the body. Mediators are responsible for ongoing interactions of different cell types and for amplification effects through their networks and feedback cycles, finally leading to a sustained inflammation and multiple organ damage in the body. In the setting of trauma/shock, many activators including bacterial as well as non-bacterial factors may be present that will induce local and systemic inflammatory responses. Although the potential role of bacteria/endotoxin translocation and its clinical relevance remains controversial, many lines of evidence support the concept that the gut may be the reservoir for systemic sepsis and subsequent MOF in a number of pathophysiologic states.
In a prospective, randomized trial, recombinant human superoxide dismutase (rhSOD, 3000 mg/day, Grünenthal, Aachen, Germany) or placebo was given intravenously during 5 days after multiple injuries (Injury Severity Score [ISS] > or = 27; 24 patients). Manifestation of multiple organ failure (MOF) and posttraumatic inflammatory response were evaluated over 14 days. No side effects were noted by continuous infusion of rhSOD, which allowed high SOD plasma levels (24.77 +/- 9.43 mg/L) compared with controls (0.03 +/- 0.02 mg/L). Multiple organ failure was attenuated by rhSOD treatment in respect to cardiovascular and pulmonary functions. Additionally, intensive care therapy was shortened from 30 days (Q25: 15; Q75: 37) to 21 days (Q25: 12; Q75: 41). A secondary increase of inflammatory mediators (e.g., C-reactive protein, polymorphonuclear [PMN]-elastase, phospholipase A2), as observed at the end of the first week in the placebo group, was reduced by rhSOD therapy. The results reveal an attenuation of organ failure after trauma, most likely by decreasing the release of inflammatory mediators and reduction of leukocyte-mediated organ injury. These preliminary results, while promising, need to be confirmed in a larger number of patients.
Multiple-organ failure (MOF), defined as the failure of initially uninvolved organs, is the final step of definitive and massive liver necrosis. Emergency liver transplantation (ELT) has radically modified the outcome of acute liver failure and early primary graft failure, but the results of ELT in cases of MOF are unknown. From May 1988 to June 1993, 243 patients underwent a liver transplantation (LT). Thirty-seven patients (15.2%) who had an acute liver necrosis complicated by a MOF underwent an ELT. Twenty-one patients were children. An emergency retransplantation was performed in 16 patients. Three or 4 organ-system failures (OSF) were present in 13 patients. Before ELT, the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 26.3 +/- 5.1. Six-month and 1-year survival rates were 37.8% and 25.9%, respectively, after ELT complicated by MOF, and 78% and 73.5%, respectively, in other cases of LT. Twenty-six patients had surgical complications (70%), whereas thirty-one patients had medical complications (84%). Twenty-two patients died during the postoperative period (60%). Before ELT, infection (P < .05), cardiovascular failure (P < .03), and more than two OSF (P < .05) were more frequent in patients who died after intervention. The APACHE II score (P < .05) and the length of stay in the intensive care unit before ELT (P < .05) were lower among survivors. In the context of liver allograft shortage, our results suggest that an ELT should not be performed in patients with cardiac failure, more than two OSF, or an APACHE II score higher than 30.
HYPOTHESIS: Multiple organ dysfunction (MOD) within 48 hours of injury is a reversible physiologic response to tissue injury and resuscitation. DESIGN: A prospective 10-year inception cohort study ending September 2003. SETTING: Regional academic level I trauma center. PATIENTS: One thousand two hundred seventy-seven consecutive trauma patients at risk for postinjury multiple organ failure (MOF). Inclusion criteria were being 16 years and older, being admitted to the trauma intensive care unit, having an Injury Severity Score higher than 15, and surviving more than 48 hours after injury. Isolated head injuries were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Development of postinjury MOD as defined by a Denver MOF score of 4 or higher within 48 hours of injury and MOF as defined by a Denver MOF score of 4 or higher more than 48 hours after injury. RESULTS: Postinjury MOD and MOF were diagnosed in 209 (16%) and 300 (23%) patients, respectively. Age, Injury Severity Score, and 12-hour blood transfusion requirements were significantly higher among patients who developed MOD and MOF. Of the 209 patients who developed MOD, 134 (64%) progressively developed MOF while 75 (36%) had MOD resolve within 48 hours. CONCLUSION: Multiple organ dysfunction during resuscitation is a reversible response to severe injury and often resolves during the resuscitation period.
OBJECTIVE: To determine how immediate enteral nutrition (EN) affects gut permeability and the development of multiple organ failure (MOF) in multiply injured patients. DESIGN: Prospective, randomised clinical trial. SETTING: 20-bed surgical intensive care unit (ICU), university hospital. PATIENTS: 28 consecutive multiply injured patients, admitted in shock and stabilised in 6 h. INTERVENTIONS: Patients were randomly assigned to EN started not later than 6 h after admission to the ICU (group A), and to EN started later than 24 h after admission (group B). MEASUREMENTS AND MAIN RESULTS: The lactulose/mannitol (L/M) test was performed in patients on days 2 and 4 after trauma, and in 5 healthy volunteers. MOF scores were calculated daily. The mean MOF score from day 4 onwards was 1.84 in group A versus 2.81 in group B (p < 0.002), and was correlated with the time of initiation of EN after injury and the L/M ratio on day 2. The median L/M ratio on day 2 was 0.029 for group A and 0.045 for group B, while on day 4 it was 0.020 and 0.060, respectively. On day 2 after trauma, the L/M ratio was significantly higher in group B (p < 0.05) than in normal volunteers (median 0.014) and was positively correlated with the time of starting EN. CONCLUSIONS: In contrast with normal volunteers, the patients started on EN later than 24 h after admission to the ICU demonstrated increased intestinal permeability on the second day after sustaining multiple injury. Also, they had a more severe form of MOF than the group placed on EN immediately upon admission. However, early EN had no influence on the length of ICU stay or the time of mechanical ventilation.
Multiple organ failure (MOF) is a critical condition developing in patients with overwhelming bodily injury resulting from major surgical insult, severe trauma, extensive burns, acute pancreatitis, and sepsis. It has recently become evident that the host response to such injury is the main pathogenetic factor contributing to the development of MOF. The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-1 are known to play a pivotal role in the pathogenetic mechanisms of MOF. In response to bodily injury, macrophages produce and release TNF and IL-1, which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators. The resultant systemic inflammation may develop into MOF mainly through neutrophil-endothelial cell interaction when the primary injury is overwhelming or a second inflammatory insult such as sepsis triggers an exacerbated inflammation. It has recently been confirmed that the transcription factor NF-kappaB is involved in the up-regulation of a variety of proinflammatory genes and that cell-mediated immunity is down-regulated in the event of major bodily injury through a shift in the balance between T helper 1 (Th1) and Th2 cytokine response patterns. The molecular immunological mechanisms by which these factors participate in the development of MOF should be characterized.
OBJECTIVE: To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.
Multiple-system organ failure is associated with progressive defects of cellular metabolism involving several organ systems. The metabolic failure is caused by a neural-hormonal reaction to trauma and sepsis and by humoral mediators damaging cell metabolism. Involved are catabolic hormones like catecholamines, cortisol and glucagon as well as the humoral mediators interleukin and arachidonic acid metabolites. There is an increase in resting energy expenditure and a derangement of utilization and production of adenine nucleotides. Severe injury, sepsis and multiple-system organ failure are associated with a 30-40% decreased content of energy rich phosphates in different tissues. The low energy charge potential is caused by the inability to use nutritional substrates adequately. Relative clearance and oxidation of glucose will advance fatty infiltration of the liver. Clearance and oxidation of fat is normal or often increased. If illness is progredient fat utilization will be disturbed. Although protein synthesis is increased in critical ill patients, due to excessive proteolyses net protein loss occur. In preterminal patients the ability of the liver to synthetize protein decreases, concentrations of several free amino acids in plasma increase, while the clearance for amino acids decreases.
Multiple organ failure syndrome (MOFS) has been alluded to since the early 1940s. It was recognized as a progressive failure to organs in the mid 1970s. Mortality from this syndrome increases proportionally, as the number of failed organs increases. Therapies to prevent MOFS and current concepts about treating failures of individual organs will be presented. Data sources were retrieved from critical care and surgical literature using MEDLINE from 1966 to the present. Searches were confined to English. Several promoters of MOFS are related to the care of gynecologic patients, especially sepsis and hemorrhage. Treatment strategies, especially those related to pulmonary, gastrointestinal, renal, cardiovascular, and nutritional aspects are discussed. Outcome and prognosis may be affected if recognition and therapeutic intervention are initiated early in the clinical course. The ability to prognosticate outcome is related to the number of organs involved. Gynecologists should have clear knowledge of the prognosis of progressive organ failure in order to appropriately counsel the patient and her family.
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BACKGROUND: Postinjury multiple organ failure (MOF) is a result of a dysfunctional inflammatory response to severe injury and shock. Acute lung injury is thought to promote further organ dysfunction by the systemic release of inflammatory mediators from injured lung tissue. Although clinical evidence supports this model, a clear understanding of the relationship between lung dysfunction and multiple organ failure has yet to be defined. We hypothesized that respiratory dysfunction is an early obligate event in the progression of postinjury MOF. METHODS: Data were collected prospectively on 1,344 trauma patients at risk for postinjury MOF. Inclusion criteria were age greater than 16 years, trauma intensive care unit admission, Injury Severity Score greater than 15, and survival longer than 48 hours. Isolated head injuries and head injuries with an extracranial abbreviated injury score of less than 2 were excluded. Daily physiologic and laboratory data were collected through surgical intensive care unit day 28 and clinical events were recorded thereafter until death or hospital discharge. Organ failure was characterized using the Denver MOF scale. RESULTS: Organ dysfunction was observed in 1,011 (75%) of 1,344 patients. Lung dysfunction was observed in 951 (94%) patients with 1 or more organ dysfunctions and 598 (99%) of 605 patients with 2 or more organ dysfunctions. Lung dysfunction preceded heart, liver, and kidney dysfunction by an average of 0.6 +/- 0.2 days, 4.8 +/- 0.2 days, and 5.5 +/- 0.5 days, respectively. The severity of lung dysfunction correlated with the severity of heart, liver, and kidney dysfunction, and the number of other dysfunctional organ systems. CONCLUSIONS: Postinjury respiratory dysfunction is an obligate event that precedes heart, liver, and kidney failure. The severity of other organ dysfunction is related directly to the severity of respiratory dysfunction. These data implicate lung dysfunction as central to the promotion of pathogenic inflammation and the development of postinjury MOF.
Multiple organ failure is a major threat to the survival of patients with sepsis and systemic inflammation. In the UK and in the USA, mortality rates are currently comparable with and projected to exceed those from myocardial infarction. The immune system combats microbial infections but, in severe sepsis, its untoward activity seems to contribute to organ dysfunction. In this Review we propose that an inappropriate activation and positioning of neutrophils within the microvasculature contributes to the pathological manifestations of multiple organ failure. We further suggest that targeting neutrophils and their interactions with blood vessel walls could be a worthwhile therapeutic strategy for sepsis.