The role of the lung in postinjury multiple organ failure

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.     

Age of transfused blood is an independent risk factor for postinjury multiple organ failure

BACKGROUND: Blood transfusion has repeatedly been demonstrated to be an independent risk factor for postinjury multiple organ failure (MOF). Previously believed to represent a surrogate for shock, packed red blood cell (PRBC) transfusion has recently been shown to result in neutrophil priming and pulmonary endothelial cell activation. We have previously observed that the generation of inflammatory mediators is related to the length of PRBC unit storage. The purpose of this study was to determine if age of transfused PRBC is a risk factor for the development of postinjury MOF. METHODS: Using our prospective database of trauma patients at risk for developing MOF, we identified patients who developed MOF (MOF+) and received 6 to 20 units of PRBCs in the first 12 hours following injury. A similar cohort of patients, matched for ISS and transfusion requirement, who did not develop MOF (MOF-) were also identified. The age of each unit of PRBC transfused in the first 6 hours was determined. Multiple logistic regression was performed to determine if age of transfused blood is an independent risk factor. RESULTS: Sixty-three patients were identified, 23 of whom were MOF+. There was no difference in ISS and transfusion requirement between MOF+ and MOF- groups. MOF+ patients, however, were significantly older (46+/-4.7 years versus 33+/-2.3 years). Moreover, mean age of transfused blood was greater in the MOF+ patients (30.5+/-1.6 days versus 24+/-0.5 days). Similarly, the mean number of units older than 14 and 21 days old were greater in the MOF+ patients. Multivariate analysis identified mean age of blood, number of units older than 14 days, and number of units older than 21 days as independent risk factors for MOF. CONCLUSION: The age of transfused PRBCs transfused in the first 6 hours is an independent risk factor for postinjury MOF. This suggests that current blood bank processing and storage technique should be reexamined. Moreover, fresh blood may be more appropriate for the initial resuscitation of trauma patients requiring transfusion.     

Decreased progression of postinjury lung dysfunction to the acute respiratory distress syndrome and multiple organ failure

BACKGROUND: Postinjury organ dysfunction is a result of unbridled systemic hyperinflammation. According to the two-event construct, patients are resuscitated into an early vulnerable window of systemic hyperinflammation (primed) in which a second otherwise innocuous event precipitates uncontrolled hyperinflammation, leading to secondary organ damage and dysfunction (activated). Recent efforts to decrease postinjury morbidity have focused on limiting the potential of second events and systemic inflammation. We hypothesized that the collective effects of recently implemented therapeutic strategies have resulted in decreased activation of the systemic inflammatory response relative to priming in recent years. METHODS: Data were collected prospectively on trauma patients at risk for postinjury multiple organ failure (MOF). Inclusion criteria were age >15 years, trauma intensive care unit admission, Injury Severity Score >15 and survival >48 hours. Isolated head injuries and head injuries with an extracranial abbreviated injury score <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 with the use of the Denver MOF Scale. Acute respiratory distress syndrome (ARDS) was defined according to the consensus definition. RESULTS: Over a 6.5-year period 897 patients were studied; 271 (31%) developed ARDS, and 226 (25%) developed MOF. Early lung dysfunction, as a measure of systemic priming, did not change over the study period. In contrast, the incidence of ARDS and MOF decreased from 43% to 25% and 33% to 12%, respectively. The incidence of early MOF decreased from 22% to 7% over the study period. CONCLUSIONS: Priming of the postinjury inflammatory response is an early event and is primarily influenced by the injury itself. Recent advances in postinjury care such as judicious blood transfusion, lung protective ventilation, treatment of adrenal insufficiency, and tight glucose control are known to attenuate systemic inflammation. Step-wise adoption of these therapies is coincident with a decrease in the destructive processes resulting in ARDS and MOF. The global effect is a decrease in activation of the systemic inflammatory response over recent years.     

The role of the gastrointestinal tract in postinjury multiple organ failure

Despite intensive investigation, the pathogenesis of postinjury multiple organ failure (MOF) remains elusive. Laboratory and clinical research strongly implicate that the gastrointestinal tract plays a pivotal role. Shock with resulting gut hypoperfusion appears to be one important inciting event. While early studies persuasively focused attention on bacterial translocation as a unifying mechanism to explain early and late sepsis syndromes that characterize postinjury MOF, subsequent studies suggest that other gut-specific mechanisms are operational. Based on our Trauma Research Center observations and those of others, we conclude that: 1) bacterial translocation may contribute to early refractory shock; 2) for patients who survive shock, the reperfused gut appears to be a source of proinflammatory mediators that may amplify the early systemic inflammatory response syndrome; and 3) early gut hypoperfusion sets the stage for progressive gut dysfunction such that the gut becomes a reservoir for pathogens and toxins that contribute to late MOF.     

Incommensurate oxygen consumption in response to maximal oxygen availability predicts postinjury multiple organ failure.

Untreated flow-dependent oxygen consumption (VO2) has recently been implicated as an unrecognized risk factor for multiple organ failure (MOF). We therefore prospectively studied 39 severely injured patients with known risk factors for multiple organ failure who were subjected to an established resuscitation protocol aimed at maximizing oxygen delivery (DO2 greater than 600 mL/min.m2) to attain a VO2 goal of greater than 150 mL/min.m2. Fifteen (38%) of these high risk patients did not meet this VO2 goal by 12 hours. These nonresponding patients had significantly elevated lactate levels, suggesting defective aerobic metabolism. Of note, this blunted VO2 response despite maximal efforts to enhance peripheral oxygen availability predicted MOF. These data serve to re-emphasize the importance of the initial shock insult in causing or priming the host for the development of late MOF.     

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多器官功能障碍综合征 (ＭＯＤＳ)指机体在遭受严重创伤、休克、感染及大手术等急性损害 2 4ｈ后 ,同时或序贯性出现两个或两个以上器官功能障碍 ,不能维持内环境稳定的临床综合征 ,强调病变的动态性和可逆性。1　病因1 1　感染因素内毒素、外毒素、革兰阳性细菌细胞壁成分、病毒、真菌等导致脓毒症、脓毒性休克的发生 ,细菌及其毒素刺激体内单核巨噬细胞系统合成分泌大量细胞因子 ,形成复杂的细胞因子网络作用 ,最终导致炎症反应和组织器官损害。据报道 70 %左右的ＭＯＤＳ可由感染引起 ,特别是大肠杆菌和绿脓杆菌引起的腹腔感染 ,ＭＯＤＳ…     

Fever with multiple organ failure: not always sepsis

We present the case of a 52-year-old female admitted with fever and multiple organ failure, initially treated for presumed sepsis. However the combination of multiple organ failure, hyperthermia and vascular instability raised the suspicion of a phaeochromocytoma multisystem crisis. An emergency abdominal ultrasound in the intensive care unit disclosed a large tumour of the right adrenal. Despite specific medical treatment for the presumed adrenal emergency and multiple organ failure, the patient succumbed. Postmortem examination verified the diagnosis of phaeochromocytoma.     

Release of anti-inflammatory mediators after major torso trauma correlates with the development of postinjury multiple organ failure

BACKGROUND: Soluble tumor necrosis factor receptor (sTNFr) and interleukin-1 receptor antagonist (IL-1ra) have been identified as endogenous inhibitors of TNF-alpha and IL-1beta. While TNF-alpha and IL-1beta levels are not systematically elevated in postinjury patients who developed multiorgan failure (MOF), their involvement at the tissue level has been suggested. Our study hypothesis was that levels of sTNFr-I and IL-1ra would discriminate patients at risk for postinjury MOF. METHODS: Serial plasma levels of sTNFr and IL-1ra were measured in 29 trauma patients at high risk for postinjury MOF. RESULTS: sTNFr-I levels were higher in MOF compared with non-MOF patients at 12, 84, and 132 hours postinjury. MOF patients also had higher IL-1ra values 36, 60, 84, and 132 hours postinjury. CONCLUSIONS: Anti-inflammatory mechanisms are activated after trauma. Since increased levels of sTNFr and IL-1ra correlate with postinjury MOF, they may contribute to our understanding of the pathogenesis as well as prediction of outcome. High levels of antagonists to TNF-alpha and IL-1beta suggest tissue level involvement of these cytokines in postinjury hyperinflammation.     

Clinical characterization of acute renal failure in multiple organ dysfunction syndrome

Background Acute renal failure frequently occurs as a complication of multiple organ dysfunction syndrome (MODS). Various forms of therapy for MODS, including endotoxin absorption and anticytokine therapy, have been attempted. Methods We retrospectively studied the pathophysiologic characteristics of acute renal failure in 152 MODS patients examined in our department over the past 5 years. The diagnosis of MODS was based on the criteria of the Japanese Association for Critical Care Medicine. The diagnosis of systemic inflammatory response syndrome (SIRS) and sepsis was conducted in accordance with the definition proposed at the 1992 Consensus Conference of the American College of Chest Physicians/ Society of Critical Care Medicine. Results Acute renal failure occurred as a complication of secondary MODS with a high frequency of 76.3% (116/152 patients). Significant associations have been found between the respective frequencies of acute renal failure and disseminated intravascular coagulation occurring as complications of SIRS. An increase in the number of cases undergoing continuous hemodiafiltration was noted, in an attempt to improve the survival rate of MODS complicated with acute renal failure. Conclusion Acute renal failure seen in secondary MODS is thought to be derived from a pathogenesis differing from that of conventional intrinsic acute renal failure, such as ischemic and nephrotoxic forms. Acute renal failure associated with secondary MODS appears to be a disease entity that arises as a sequela of SIRS, similar to disseminated intravascular coagulation.     

Multiple system organ failure

Multiple system organ failure represents the final common pathway to a fatal outcome in severely infected patients. Despite the development of extensive support technology, the mortality rate in this group of patients remains high: in excess of 50 per cent. This rate underscores the need for newer treatment modalities. Numerous mediators/effectors appear to play a role in the complex evolution of the process. The independent and interactive effects of these numerous mediators/effectors remain to be elucidated. Future therapies will need to address immunomodulation of the host and biochemical manipulation of the fundamental process before significant improvement in outcome can be expected.     

Multiple organ failure still a major cause of morbidity but not mortality in blunt multiple trauma.

BACKGROUND: Multiple organ failure (OF/MOF) was found to be the major complication after blunt multiple trauma during the last 25 years and was correlated with a high mortality rate. Recently, several publications reported a decreased ARDS-related mortality, but there is little information about mortality rates from posttraumatic MOF. The purpose of this study was to describe the development of MOF-related death after blunt multiple trauma during the last 25 years. METHODS: Blunt multiple trauma patients with an Injury Severity Score (ISS) > 15 points were included in this evaluation. According to the year of trauma, the population was divided into five groups: years 1975-1980 (n = 317), years 1981-1985 (n = 308), years 1986-1990 (n = 246), years 1991-1997 (n = 368), and years 1998-1999 (n = 122). Main outcome measurements were death, cause of death, and length of ICU stay. Patients dying within the first 24 hours after trauma were excluded. All data indicated in the Results section are presented as mean +/- SEM. Continuous variables were compared by ANOVA.Ordinal variables were analyzed by chi2 contingency table analysis and, if significant, subsequently by Fisher's exact test (two-tailed test, p < 0.05). RESULTS: Mean ISS remained unchanged between 1975-1980 (ISS 29 +/- 1) and 1998-1999 (ISS 31 +/- 1) (p = 0.56). During the observation period, the mean age increased from 33 +/- 1 years (1975-1980) to 40 +/- 2 years (1998-1999) (p = 0.03). The overall incidence of OF/MOF slightly increased from 25.6% (1975-1980) to 33.6% (1998-1999) (p = 0.1). Length of ICU stay was not different between 1975-1980 (LOS: 14 +/- 1 d) and 1998-1999 (LOS: 19 +/- 2 d) (p = 1.0). The overall mortality decreased significantly, from 28.7% (1975-1980) to 13.9% (1998-1999) (p < 0.001). While the mortality due to severe head injuries remained unchanged (1975-1980, 8.2%; 1998-1999, 9.0%) (p = 0.85), mortality due to OF/MOF decreased significantly (p < 0.001), from 18.0% (1975-1980) to 4.1% (1998-1999). The age of patients dying from OF/MOF increased significantly (p = 0.04) during the observation period, from 44 +/- 3 years (1975-1980) to 63 +/- 6 years (1998-1999). CONCLUSION: Although MOF incidence remains unchanged, there is a significant fall in MOF-related mortality in patients with severe trauma, and death from single organ failure is virtually absent. Severe brain injury is now the leading cause of death in patients with severe multiple injuries admitted to the ICU.     

Postinjury multiple organ failure

Postinjury multiple organ failure (MOF) became prevalent as the improvements in critical care during the 1970s made it possible to keep trauma patients alive with single organ injury. Enormous efforts invested in laboratory and clinical research made it possible to better understand the epidemiology and pathophysiology of the syndrome. This has translated to improved strategies in prediction, prevention and treatment of MOF. With changes in population demographics and injury mechanisms and improvements in trauma care, changes in the epidemiology of MOF are also becoming evident. Significant improvements in trauma patient management decreased the severity and mortality of MOF, but the syndrome still remains the most significant contributor of late postinjury mortality and intensive care unit resource utilisation.This review defines the essential MOF-related terminology, summarises the changing epidemiology of MOF, describes our current understanding of the pathophysiology, discusses the available strategies for prevention/treatment based on the identified independent predictors and provides future directions for research.