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[Multiple organ failure syndrome: correlation of mortality and the Modified Criteria for Multiple Organ Failure].

Seventy-two patients from one month to 15 years of age that according with the Modificated criterion of multiple organ failure (MCMOF) had two or more organ failures were studied. They were divided into two groups: Group I consisted of 55 patients that survived and group II of 17 patients that died. In both groups, the MCMOF was determinated upon admission and discharge, as well as the maximum obtained during the evolution. The comparison of both groups, with respect to the number of organic failures presented and the points of MCMOF showed highly significant differences with p less than 0.001, found in group I: 1.27 +/- 0.96 organ failures and a value of 4.84 +/- 2.92 of the MCMOF and in the group II: 3.84 +/- 1.59 organ failures and 25.68 +/- 7.57 points of the MCMOF respectively. The comparison between the number of organic failures at admission and discharge showed significant differences in both groups, having the tendency to decrease in group I from 1.87 +/- 1.01 to 0.56 +/- 0.60 and in the group II to increase from 3.41 +/- 1.46 to 4.35 +/- 1.45. The same phenomenon was observed for the values of the MCMOF with a qualification of 7.72 +/- 5.36 to 1.87 +/- 1.82 in a group I and from 18.94 +/- 10.31 to 33.38 +/- 8.27 in group II. Spearman correlation coeficient between the number of organic failures and values of the MCMOF showed and r = 0.99 and equivalent p less than 0.001, highly significant.

Adolescent↗

[Clinical patterns and stages of multiple organ failure in the elderly].

Multiple organ failure in the elderly (MOFE) is a new clinical syndrome different from multiple organ failure (MOF) caused by trauma occurring most often in young and mid-aged persons. The authors retrospectively analysed 158 cases of MOFE hospitalized in the past 12 years and commented on its definition, diagnostic criteria, clinical patterns and stages. The suggested definition of MOFE is the sequential 2 or more organs failure within a short period in the elderly patients (greater than or equal to 60 years old) with multiple organ chronic diseases in the presence of aging of organs and age-related malfunction. The most common precipitating factors are pulmonary infections and acute attack of chronic cardiac, cerebral and renal diseases. The interval between failures of various organs is mostly less than 10 days and seldom longer than 1 month. MOFE has 3 different patterns: rapid pattern with single phase; delayed pattern with two phases and recurrent pattern with multiple phase. In the last pattern the patients suffer from multiple attacks of multiple organ failure. It is only seen in MOFE, but not in MOF. The presentation of this particular pattern is related to the following facts: (1). A few organs or only the heart and lungs are involved. (2) Kidney, brain and hemopoietic system etc. usually with poor prognosis are not involved. (3) The age of patients are relatively younger. (4) More resuscitation experiences have been accumulated and better resuscitation measures are available. The clinical course of MOFE can be divided into 3 stages: prefailure stage (stage I), failure compensations stage (stage II) and decompensation stage (stage III).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure.

BACKGROUND: Postinjury multiple organ failure (MOF) is the result of a dysregulated systemic inflammatory response in which primed neutrophils (PMNs) are sequestered in tissues, vulnerable to activation through secondary insults. Apoptosis is critical to the normal clearance of these sequestered PMNs. Conversely, dysfunctional apoptosis prolongs the PMN functional life span, potentially exacerbating PMN-mediated tissue injury and the development of MOF. We hypothesized that severe trauma, in addition to priming PMNs, provokes dysfunctional PMN apoptosis. METHODS: Neutrophils were harvested daily from 12 severely injured patients at high risk for MOF, cultured for 24 hours, and assessed for apoptosis with use of acridine orange-ethidium bromide staining and fluorescence microscopy. Priming for elastase release was measured in freshly isolated patient PMNs. Plasma from patients was assessed for its ability to delay apoptosis of normal PMNs. RESULTS: Four patients (33%) had MOF. Neutrophil apoptosis was profoundly delayed in severely injured patients throughout the 5-day study period. Priming for elastase release was augmented concomitantly. Patients' plasma delayed apoptosis of normal PMNs. CONCLUSION: In patients at high risk for postinjury MOF, PMNs are not only primed for cytotoxicity but also resist apoptosis. The dysfunctional apoptosis is attributed, at least in part, to a plasma-borne mediator. The net effect may facilitate hyperinflammatory organ injury.

Adolescent↗

Secretory phospholipase A2 activity correlates with postinjury multiple organ failure.

UNLABELLED: Postinjury multiple organ failure (MOF) may result from overwhelming systemic hyperinflammation. Secretory phospholipase A2 (sPLA2) produces many inflammatory lipid mediators, and levels have been correlated with both the severity of patient injury and postinjury mortality. The objective of this study was to characterize the plasma activity of sPLA2 type IIa in severely injured patients and to determine whether the activity of this enzyme correlates with the subsequent development of MOF. PATIENTS: Seventeen severely injured patients at known risk for MOF had blood sampled on postinjury days 0, 1, 2, 3, and 5. DESIGN: sPLA2 activity was sequentially measured and correlated with MOF scores. RESULTS: Six patients (35%) developed MOF. In comparison with non-MOF patients, MOF patients had elevated sPLA2 activity beginning 36 hrs postinjury (MOF sPLA2, 2.4 +/- 0.97, vs. non-MOF sPLA2, 0.86 +/- 0.16 active units (AU); p < .05) and continuing over the ensuing 5 days. To rule out the possibility that stored blood components required for patient resuscitation was the source of sPLA2, the sPLA2 was measured in packed red blood cells, platelet concentrates, and fresh frozen plasma over the routine storage time. None of the products tested had elevated levels of sPLA2 compared with fresh plasma from healthy adult volunteers. CONCLUSIONS: We conclude that increased sPLA2 activity is associated with the development of postinjury MOF.

Adult↗

[Liver failure as part of multiple organ failure following polytrauma].

In the last few years there has been increasing evidence that adult respiratory distress syndrome is only part of a much more complex syndrome called multiorgan failure (MOF). Since renal and lung failure have become rare because of our increased understanding of the pathomechanisms involved and the treatment changes, liver dysfunction has been noted more often. In a clinical trial with 38 patients with severe trauma, we investigated liver function using ordinary parameters like the transaminases, bilirubin, etc. To define one group with MOF and one without we used the Goris MOF Score. In both groups glutamate dehydrogenase (GLDH) was increased initially up to 14 U/l, indicating hypoxia of the liver cells right after trauma. From day 6 on, a second increase up to 12 U/l of GLDH in the MOF group was evidence of liver cell dysfunction. The glutamine oxalacetic transaminase (GOT) level remained normal in both groups after an initial increase of up to 60 U/l in both groups. As 30% of serum GOT is released by muscle cells, the initial peak values could be due to direct muscle trauma, because an initial increase was noted even in the creatinine kinase. A decrease in clotting factor V down to 30% on day 8 in the MOF group indicated that the metabolic synthesis activity of the liver was lower. Bilirubin increased in the MOF group from day 5 on up to 240 mumol/l on the day 14. As this increase was not parallel to the gamma glutamyl transferase (Gamma BT) level, the reason for the bilirubin increase may be dysfunction of the liver cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Does drainage of intraabdominal pus reverse multiple organ failure?

Intraabdominal abscess induced multiple organ failure in 21 patients. Sepsis was most often due to perforation of the colon and was located with almost equal frequency in the upper and lower abdomen. Four patients died after single laparotomy for drainage. Seventeen were drained operatively more than once (average 3.4 operations) at mean intervals of 10 days. Sixteen of the 21 patients (76 percent) died with multiple organ failure despite drainage. Organ function improved temporarily in only one patient. Autopsy showed that pus had persisted or recurred in three patients. No significant predictors of survival were identified, although the advantage appears to lie with the younger patient in whom multiple organ failure develops relatively late after sepsis (mean 13 days) and who needs ventilatory assistance for less than 1 week. The location, size, and bacteriologic characteristics of abscesses do not appear to influence outcome. This study shows that early and repeated drainage of intraabdominal pus will not reverse multiple organ failure in the majority of patients.

Abdomen↗

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.

Critical Care↗

The asymmetrical dimethylarginine (ADMA)-multiple organ failure hypothesis.

Development of multiple organ failure is the most complex problem in critically ill patients, and is associated with a high mortality. Asymmetrical dimethylarginine (ADMA) is an endogenously produced inhibitor of nitric oxide synthase, of which the clinical importance is currently being revealed. In Nijveldt et al. (The liver is an important organ in the metabolism of asymmetrical dimethylargenine (ADMA) Clin Nutr 2003; 22: 17-22) we showed that plasma ADMA concentration is elevated in critically ill patients and significantly related to hepatic function. Moreover, plasma ADMA concentration emerged as a strong and independent risk factor for ICU mortality in these patients. Here, we hypothesize that accumulation of ADMA is a causative factor in the development of multiple organ failure by interfering with important physiological functions of nitric oxide production.

Arginine↗

[Clinical feature and laboratory findings of multiple organ failure].

The pathology of multiple organ failure consists of tissue-cell damage (disruption of energy metabolism) and severe infections (host exhaustion). The impairment of the TCA cycle was mild in two-organ disease but was nearly arrested in three-organ disease, and the cells are considered to have been in lactic acidosis with a shift of the glycolytic system from pyruvate to lactate. Significant differences were observed also in the number and the function of lymphocytes between two-organ and three-organ diseases. Therefore, in multiple organ failure, infections are considered to worsen as the ability of antigen recognition is impaired and differentiation of B cells into antibody-producing cells is inhibited with a decrease in lymphocytes. The phagocytic activity of neutrophils did not decrease unless leukocytes were reduced.

Citric Acid Cycle↗

Clinical features of multiple organ failure in the elderly.

Multiple organ failure (MOF) in the elderly is a new syndrome evolved from multiple organ chronic diseases on the basis of multiple organ dysfunction in the aged. Its characteristics are clinically different from those of MOF due to serious trauma. 122 cases of MOF were analysed retrospectively and their clinical features discussed. MOF with a long course is the natural presentation in many of the elderly before death. Its main precipitating factors are pulmonary infection, metastatic carcinoma, cardiac attack, etc. The sequence of a failure in organs is heart, lung, kidney, liver, etc. The mortality is similar to that of MOF due to trauma. However, those suffering from 4-organ failure can still survive, and instead, the renal failure can be mostly fatal. More attention should be paid to the prevention of MOF in the elderly so as to shorten its developing course.

Aged↗

[Multiple organ failure after valve replacement].

Multiple organ failure (MOF) after valve replacement during 1980-1991 showed. Incidences involving 2, 3 and over 3 organs were 17.1%, 5.6%, 4.3% with related mortalities 12.0%, 18.5%, 76.2%. This analysis focused on cases of more than 3 organ failures. More than 3 organ failure, the most dreadful complications, can be divided clinically into three types: acute (type I), deteriorating (type II) and pulmonary infection (type III). In MOF the function of heart and lung is primarily depressed after surgery. So the predisposing factors of MOF are acute pump failure and hypoxemia, and likely the "triggering factor" is infection especia pulmonary infection. The latter re-endangers the organs just recovering from the primary blows. So prevention of pulmonary infection is of same importance as treatment of pump failure and hypoxemia.

Adult↗

Multiple organ failure in septic patients.

Multiple organ failure (MOF) is the main cause of death in ICUs, especially affecting septic patients. It is strongly related to number of systems with failure, type of system involved, risk factors such as age, previous chronic diseases, delayed or inadequate resuscitation, persistent infection, immune suppression, and others. The prognoses is worse for patients rather than in elective or emergency surgical patients. The objective of this article is to provide data from our university teaching hospital ICU related to the incidence of septic patients, the distribution of MOF, and distribution of failure among each of the organs. The mortality rate, relationship between mortality and age, and mortality and types of organs affected were evaluated. The main bacterial causes of sepsis were also identified. A retrospective evaluation was done of 249 patients admitted to the ICU in a 4 month period during 1999. Fifty four patients had sepsis diagnosed by ACCS/SCCM criteria. There were 37 men and 17 women; 24 medical and 30 post-surgical patients (9 after elective surgery and 21 emergency patients). APACHE II score was calculated on admission and MOF, measured for the first five days, was diagnosed using Marshall and Meakins criteria. The statistical method used was non-parametric Mann-Whitney test, p<0.05 was considered significant. The incidence of sepsis was recorded in 54/249 patients (22%). Thirty of these 54 patients (56%) died. Death occurred in 2 of 11 patients with one organ failure (18%), in 14/27 with 2 or 3 organ failures (52%), and 14/16 with 4 or more organ failures (88%). None of the three patients 15 to 20 years old died, 17/32 (55%) patients age 21-60 years, and >61 years 13/19 (68%), died. There were 23 patients with positive bacterial culture. The most frequent bacteria found were: Pseudomonas aeruginosa (5), multiresistant Acinetobacter baumanii (3), Staphylococcus epidermidis (3), Enterobacter aerogenes (3), Klebsiella pneumoniae (2) and multiresistant Staphylococcus aureus (2). The mean value +/- SD of APACHE II (mortality risk) for survivors was 21 +/- 18 and for non-survivors 42 +/- 26 (p<0.001). We conclude that MOF due to sepsis in an ICU is frequent, with high mortality related to the number of failing organs, age and high APACHE II.

Age Factors↗

Pulmonary responses to overventilation in late multiple organ failure.

BACKGROUND: Patients with multiple organ failure (MOF) require mechanical ventilation for several days. The enormous significance of the ventilation strategy for the outcome of these patients is well appreciated. However, most studies have focused on the onset and the early phase of MOF. It was the aim of the current study to investigate the effect of ventilation in the course of MOF. METHODS: Using a model where mice develop MOF 7-14 days after intraperitoneal injection of zymosan, the authors analyzed lung functions, signaling pathways, and mediator release in response to protective ventilation (end-expiratory pressure -3 cm H2O; end-inspiratory pressure -10 cm H2O) and overventilation (-22.5 cm H2O) in isolated lungs ex vivo. RESULTS: On day 7, pulmonary compliance, pulmonary resistance, and tidal volume were normal, but vascular resistance was elevated compared with untreated animals. During ex vivo ventilation, these lungs showed enhanced nuclear factor-kappaB activation, Akt kinase phosphorylation, and cytokine release, and this was further aggravated by overventilation. After 14 days, zymosan-treated animals were characterized by pulmonary hypertension, reduced tidal volume, elevated pulmonary resistance, and increased mediator production. However, in these lungs, neither nuclear factor-kappaB activation nor cytokine production where enhanced by overventilation. CONCLUSIONS: The zymosan model is characterized by pulmonary inflammation, diminished lung functions, and chronic hypertension. Mechanical ventilation with high distending pressures further augmented cytokine production in this chronic model of MOF only if it significantly augmented tidal volume. The authors speculate that these findings may be explained on the basis of different degrees of lung stretch.

Animals↗

Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure.

Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis-induced multiple organ failure. Ten critically ill patients suffering from sepsis-induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n = 10) of metabolically healthy age- and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and IV and concentrations of ATP, creatine phosphate, and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower, respectively, in intercostal muscle of the patients but not in leg muscle compared with controls. The activity of complex IV was 30% lower in leg muscle but not in intercostal muscle. Concentrations of ATP and creatine phosphate were, respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg muscle but not in intercostal muscle. We conclude that both leg and intercostal muscle show a twofold decrease in mitochondrial content in intensive care unit patients with multiple organ failure, which is associated with lower concentrations of energy-rich phosphates and an increased anaerobic energy production in leg muscle but not in intercostal muscle.

Adenosine Triphosphate↗

Hepatic drug disposition in multiple organ failure.

In 15 patients with multiple organ failure of septic etiology, some principal partial hepatic functions of drug disposition were measured by the test substances galactose, indocyanine green, theophylline and 4-methylumbelliferon. Glucuronidation was not impaired in any case, whereas flow-limited and capacity-limited drug elimination can be influenced. Drug monitoring and intense clinical observation seem necessary to improve drug therapy and the outcome of patients with multiple organ failure.

Adult↗

Multiple organ failure after liver transplantation.

OBJECTIVE: To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization. DESIGN: Retrospective cohort study. SETTING: Surgical intensive care unit in a tertiary care university hospital. PATIENTS: Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death. CONCLUSIONS: Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome.

APACHE↗