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PubMedDate not supplied

[Lactate kinetics during constant hemodiafiltration in critically severe patients with the systemic inflammatory response syndrome and multiple organ failure].

High-volume hemodiafiltration is a new approach to the treatment of critical patients with generalized inflammatory reaction and multiple organ failure. Increase of the liquid exchange during the procedure is fraught with the development of secondary metabolic disorders in cases when lactate-based buffer is used (with high amounts of lactate). This study was undertaken to evaluate the consequences for the acid-base balance in patients with hypoxia and circulatory failure. Twelve patients (6 men and 6 women) with APACHE II score 25 were examined. The major treatment modality was continuous hemodiafiltration. The results indicate that lactate-buffered solutions can be used in critical patients, because they do not cause a notable increase in the blood lactate levels due to its good utilization. Moreover, it is associated with correction of disorders in acid-base balance. No negative clinical consequences were observed after using lactate anion in high concentrations as the major buffer compound.

Acid-Base Equilibrium↗

PubMed1996

[Endotoxinemia and multiple organ failure after polytrauma].

Despite successful management of early complications in polytraumatized patients and obvious reduction of early death, lethality in the late course of the disease--frequently as a result of multiple organ failure (MOF)--remains generally unaffected. Concerning the pathogenesis of sepsis and MOF, there is some evidence that a central role is played by endotoxin. A series of 32 patients with severe polytraumatic injury (Hannover Polytrauma Score > 20 points) comprised the study group. Endotoxin was measured hourly over the first 24 hours. The first measuring point was four hours after injury at the latest. Endotoxin levels were determined by a quantitative turbidimetric limulus assay. The Goris MOF score reached between the 8th and 10th day after injury was used for evaluation of the severity of MOF. Thirty of the 32 patients showed episodes of endotoxemia during the measuring period. There was a strong correlation between observed endotoxin peak concentrations, on the one hand, and outcome as well as positive predictive value (PPV) concerning development of MOF, on the other hand. If the peak concentration was greater than 10 pg/ml, the PPV reached 100%. No patient survived a peak concentration greater than 12 pg/ml. Endotoxemia during the early phase after polytraumatic injury is a frequent phenomenon. It appears to be possible that measurement of endotoxin peak concentration during the early phase gives some indication of the development of MOF and the outcome of these patients.

APACHE↗

PubMed2005

Roles of MMP-2/-9 in cardiac dysfunction during early multiple organ failure in an ovine animal model.

Biventricular dilation and severe cardiac dysfunction are observed during septic shock. However, when endotoxemia and vasoconstrictor-masked hypovolemia work in concert in the pathogenesis of shock, the clinical scenario is more adverse compared to one of the insults acting alone. Matrix metalloproteinases (MMPs) are involved in chronic and acute heart failure by degrading the mechanical scaffold of the heart and several intracellular proteins. Therefore, the roles of MMP-2, MMP-9, MT1-MMP, focal adhesion kinase (FAK), and Paxillin in hearts of early multiple organ failure induced by norfenefrine-masked hypovolemia and endotoxemia were investigated in an ovine model. Experimental groups included (1) norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO) (n=6), (2) norfenefrine-masked hypovolemia without endotoxemia (NMH) (n=6), (3) recurrent endotoxemia during normovolemia (ENDO) (n=6), and (4) healthy untreated controls (CON) (n=3). Apoptosis was determined by TUNEL-staining. Gel zymography revealed significantly increased MMP-2 activity in NMH+ENDO compared to ENDO and controls. MMP-9 activity was significantly elevated in all experimental groups. MMP-2 was significantly increased at the protein level, while MMP-9 was unaltered. MT1-MMP was not significantly changed in any group. Increased MMP activities were associated with cardiac deterioration. MMP-2/-9 activity and phosphorylated Paxillin (p-Paxillin) expression correlated positively with cardiomyocyte apoptosis. This study underscores the pivotal roles of MMP in acute cardiac dysfunction during early multiple organ failure in combined vasoconstrictor-masked hypovolemic and endotoxemia shock.

Animals↗

PubMed1996

Role of the gut in multiple organ failure: bacterial translocation and permeability changes.

It is clear that increased gut permeability and bacterial translocation play a role in multiple organ failure (MOF). Failure of the gut barrier remains central to the hypothesis that toxins escaping from the gut lumen contribute to activation of the host's immune inflammatory defense mechanisms, subsequently leading to the autointoxication and tissue destruction seen in the septic response characteristic of MOF. However, the role of the gut is more than that of a sieve, which simply allows passage of bacteria and endotoxin from the gut lumen to the portal or systemic circulation. It appears, in addition, that the translocation of bacteria and endotoxin may lead to local activation of the immune inflammatory system and the local production of cytokines and other immune inflammatory mediators. These intestinally derived mediators may then exacerbate the systemic inflammatory response and potentially lead to a further increase in gut permeability. A vicious cycle of increased intestinal permeability, leading to toxic mediator release, resulting in a further increase in gut permeability is generated. Additionally, the systemic and local inflammatory cells that become activated in the gut contribute to the systemic response characteristic of the sepsis syndrome and MOF. Thus even if the immune inflammatory system, rather than the gut, is the "motor of" MOF, the gut remains one of the major pistons that turns the motor.

Animals↗

PubMed1994

Immunologic assessment of host defense impairment in patients with septic multiple organ failure: relationship between complement activation and changes in neutrophil function.

BACKGROUND: The pathogenesis of gram-negative sepsis-induced multiple organ failure (MOF) remains to be elucidated. METHODS: Blood samples were obtained from eleven patients with septic MOF, three patients with sepsis, three patients who underwent operation, and three healthy volunteers. In these patients the relationship between changes in polymorphonuclear neutrophil (PMN) function and complement activation was investigated. RESULTS: PMNs from patients with sepsis exhibited enhanced endothelial cell adhesion, enhanced chemotaxis, increased oxygen radical generation, and increased lysosomal enzyme release. Although PMNs from patients with septic MOF also exhibited enhanced adhesion and chemical mediator production, chemotaxis was markedly depressed. Complement activation in septic MOF was indicated by decreases in total complement activity and complement component 4 (C4) and increases in C3a and C4a des-Arginine. Increases in plasma concentrations of circulating immunoglobulin G immune complexes and decreases in PMN Fc gamma R expression suggest that the classic pathway is the main pathway of complement activation. On the other hand, we could not detect decreases in C4 or increases in C4a des-Arginine in patients with sepsis, suggesting that the alternate pathway is the main pathway of complement activation. Increases in serum concentrations of the membrane attack (SC5b-9) complex also suggested that activated complement itself may participate in organ injury in patients with septic MOF. Moreover, PMN up-regulation of surface inhibitory factors of complement activation likely allows these neutrophils to survive and function. CONCLUSIONS: The combination of changes in PMN function and complement activation appears to be intimately associated with the pathogenesis of septic MOF.

Adult↗

PubMed1989

[Infection as a cause of multiple organ failure. Definition, pathophysiology and diagnostic parameters].

DEFINITION: Several clinical observations support the hypothesis that bacterial sepsis is the main aetiological factor in at least half of the patients developing multiple organ failure. Sepsis is defined as the pathophysiological alterations and life-threatening clinical consequences of the action of microorganisms or their products invading the blood stream from a focus of infection. The clinical course of sepsis is highlighted by initial multiorgan insufficiency progressing to severe multiple system organ failure. PATHOPHYSIOLOGY: Pathogenetic bacteria and bacterial toxins arise from the septic focus, overcome the defence mechanisms of the body, continuously invade the blood stream, activate the biological cascade systems and initiate release of mediators from blood and tissue cells. Endotoxin and activated mediators cause endothelial and organ cell dysfunction and cell damage by at least three mechanisms: maldistribution of blood flow; cytotoxia; direct inhibition of oxygen-utilising cell enzymes. CLINICAL PICTURE: The septic disease begins with unspecific signs caused by invasion of bacteria, followed by alterations of the circulatory system, the blood clotting system, the metabolism, initiating vital organ dysfunctions and finally acute respiratory, renal, gastrointestinal, hepatic failure and septic encephalopathy. DIAGNOSIS: The clinical diagnosis of sepsis is based on the finding of an obvious septic focus with the presence of at least four of the following 5 criteria: (I) fever above 38.8 degrees C or hypothermia below 35.5 degrees C; (II) tachypnoea (greater than 24/min) or hypocapnia (PaCO2 less than 32 mmHg); (III) tachycardia (greater than 100 Bpm), (IV) leucocytosis (greater than or equal to 15.000/mm3) or leucopenia (greater than 5.000/mm3); (V) presence of at least one indicator for inadequate organ perfusion like mental alterations, hypoxaemia (PaCO2 less than 75 mmHg while breathing room air), hyperlactataemia (greater than 1,6 mmol/l), diuresis below 30 ml/h, drop in systolic blood pressure below 100 mmHg. A positive blood culture or a positive limulus test are frequent but are not considered to be obligatory for the diagnosis of sepsis.

Bacterial Infections↗

PubMed1991

[Hemopurification in the management of ARDS complicating multiple organ failure].

In the field of critical care medicine, it has been claimed that ARDS often develops as a part of multiple organ failure (MOF). Since multi-modality therapy is necessary in the management of MOF, it is also mandatory even in the management of ARDS. Among the various therapeutic approaches for patients with MOF, hemopurification is one of the most effective therapeutic tools. Various hemopurification methods such as hemodialysis, peritoneal dialysis, hemoadsorption, hemofiltration and plasma exchange have been applied in the management of MOR. However, our recent experiences suggest that continuous hemofiltration (CHF) and/or continuous hemodiafiltration (CHDF) are safest, most easily performed and effective hemopurification in the management of ARDS/MOF. The efficacy of hemopurification in the management of ARDS is summarized as follows. 1) Removal of humoral mediators and causative substances of ARDS following insults such as sepsis and trauma. 2) Treatment of pulmonary interstitial permeability edema which has been claimed to be one of the most important pathological conditions in ARDS. 3) Removal of excess water given as carrier in IVH solution and accumulating in the body. 4) Immunomodulation which has also been considered to be necessary in the treatment or prevention of ARDS.

Hemofiltration↗

PubMed1990

[Changes in organ water content in patients with postburn multiple organ failure].

Water contents of lung, heart, kidney, liver, gastro-intestines, and spleen in accident victims with good health (N = 10) and patients with postburn multiple organ failure (PBMOF) (N = 10) were measured. It was found that organ water content of all visceral organs was increased markedly in PBMOF patients. Moreover, the severity of increased organ water content was paralleled with the severity of organ failure. However, there were some differences between the results of the estimated blood volume in different organs. The pulmonary, cardiac and gastrointestinal residual blood water volumes were increased in these patients with PBMOF, indicating that congestion and/or sludging were superimposed in these organs. In contract, the renal and spleen residual blood water volumes were decreased, indicating that these organs were suffered from ischemia. On the other hand, the hepatic residual blood water volume was declined in these PBMOF without hepatic failure. However, it was increased in those with hepatic failure. These results suggested that the increase of organ water content might play an important role in the pathogenesis of organ failure.

Adult↗

PubMed1996

Blood purification for prevention and treatment of multiple organ failure.

Blood purification has been applied conventionally as an artificial kidney or artificial liver in the management of patients with multiple organ failure (MOF), and most blood purifications have been performed intermittently. Recent advances in medical engineering made it possible to perform such blood purifications continuously (i. e., 24 hours a day, 7 days a week if necessary) even in critically ill patients. This modality is referred to as continuous renal replacement therapy (CRRT) or continuous blood purification (CBP). Among many kinds of CBP, continuous hemodiafiltration (CHDF) is most useful for management of MOF, as it can be performed without serious or hazardous side effects, and improvement can be expected with it. Recently, CHDF and polymyxin B immobilized endotoxin adsorption columns were used for the prevention or treatment of MOF, with the expectation that such therapy can be effective as a countermeasure against the pathophysiologic causes of MOF. Our data and that of others clearly indicate that continuous blood purification, such as with CHDF and endotoxin adsorption, can remove or decrease the blood levels of humoral mediators, including proinflammatory cytokines, and can improve tissue oxygenation, especially oxygen consumption (VO2) among critically ill patients including those with MOF. Blood purification is also useful in the careful management of fluid, electrolytes, and acid-base balance and for the removal of metabolic wastes. Blood purification is now considered to be one of the basic therapeutic tools of critical care, equal to nutritional support with total parenteral nutrition and respiratory support without a ventilator.

Critical Care↗

PubMed2005

[Relationship between glomerular lesion and NF-kappaB p65 activity in rat multiple organ failure caused by zymosan].

AIM: To observe the relationship between NF-kappaB p65 activity and glomerular lesion in rat multiple organ failure (MOF) caused by zymosan. METHODS: Twenty female Wistar rats aged 6-8 weeks were divided randomly into two groups, ten each group. 24 hours after MOF model was induced successfully by intraperitoneal injection of zymosan-paraffin oil suspension, the rats were sacrificed and the functions of liver and kidney as well as blood gas were analysed. At the meaning time, the pathological change in renal tissues was examined by H.E, PAS, PASM and Masson staining, whereas the NF-kappaB p65 activity in glomeruli was detected by immunohistochemical staining and ELISA. RESULTS: The levels of PO(2) and pH in blood of MOF model group were significantly lower than those of control group, while the levels of serum ALT and Cr were quite to the contrary. Pathological examination showed that in MOF model rats, there were notable proliferation of glomeruli, partial sclerotic glomeruli and a large number of infiltrating inflammatory cells in glomeruli and periglomeruli. Besides, the activity of NF-kappaB p65 in rat glomeruli of MOF model group was significantly higher than that of control group(P<0.01), and the increased activity of NF-kappaB p65 was positively corelated to the cell number in glomeruli, and area density of basement membrane as well as mesangial area, but negatively correlated to the area density of capillary loop. CONCLUSION: The increase in the activity of NF-kappaB p65 may play an important role in glomerular lesions of MOF model rats caused by zymosan.

Animals↗

PubMed2006

Hyperbaric oxygen therapy prevents coagulation disorders in an experimental model of multiple organ failure syndrome.

OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy on the coagulation cascade using an experimental model of multiple organ failure syndrome (MOFS). DESIGN: MOFS was induced by zymosan (500mg/kg i.p.) in rats. HBO therapy (2ATA) was administered in a cylindrical steel chamber 4 and 11h after zymosan administration. In a separate set of experiments animals were monitored for 72h, and systemic toxicity was scored. INTERVENTION: Eighteen hours after zymosan administration, rats were killed and blood samples were used for analysis of hemocoagulative parameters, hemodynamics, and arterial blood gas. MAIN RESULTS: Zymosan administration caused MOFS by affecting the coagulation cascade, as shown by a significant increase in plasma levels of fibrinogen, tissue plasminogen activator, inhibitor of tissue plasminogen activator of type 1, and plasma levels of fibrin degradation products vs. control rats. Zymosan-induced MOFS was also characterized by a significant increase in von Willebrand antigen plasma levels vs. controls. Moreover, zymosan administration induced a significant fall in mean arterial blood pressure and alteration in blood gas values. HBO therapy significantly reduced the derangements of coagulation cascade, the fall in mean blood pressure and alteration in blood gas induced by zymosan administration. CONCLUSIONS: The hypercoagulability induced by zymosan could be responsible for organ failure and death. Our data demonstrate that HBO therapy significantly prevents the alteration in the coagulation cascade and arterial blood gas in an experimental model of MOFS.

Animals↗

PubMed2005

[Sepsis and multiple organ failure - update of current therapeutic concepts].

Severe sepsis with multiple organ dysfunctions is still the leading cause of death in non-cardiac intensive care units. The incidence is expected to rise in the future due to the growing number of older and immuno-compromized patients, the use of invasive procedures, and an increase in the percentage of aggressive or resistant microorganisms. Despite the enormous investment in critical care resources, mortality of severe sepsis remaines on a high level and ranges from 28 - 50 %. Based on the disappointing experiences with anti-inflammatory strategies, we now realize that sepsis is more than just inflammation. The new therapeutic approaches take account of this more sophisticated view of pathophysiologic changes, resulting in the modulation of the coagulation in combination with an improvement of the ICU-management of organ dysfunctions. This review discusses the therapeutic concepts, reported es exciting new interventions in the ICU setting to decrease the inacceptable high mortality in patients with severe sepsis.

Catecholamines↗

PubMed1977

Multiple organ failure.

Forty-two postoperative patients, each with demonstrable failure of two or more vital organ systems, have been studied as they define a syndrome of multiple organ failure. They typify the emerging clinical entity of patients kept alive solely by reason of specific mechanical and pharmacologic support. Trauma initiated hospitalization in 40 per cent and major bleeding, in 11 per cent. Sepsis was judged to be of etiologic significance in 69 per cent. Complications in clinical management were, in retrospect, thought to be of contributory etiologic significance in 57 per cent. Twenty-nine of 42 patients died; a mortality of 69 per cent. Mean duration of multiple organ failure was 30.5 days. Hospital cost, omitting the physician's fees, was conservatively estimated at $700 per day. Scientific, social, moral, ethical and legal factors emphasize the need to establish a statistically valid large data base concerning this new man-made syndrome which has both important scientific and social implications. This study is a first step in this direction.

Abdomen, Acute↗

PubMed2004

Increased activity of the intestinal mucosal mast cells in rats with multiple organ failure.

OBJECTIVE: This study was undertaken to evaluate the changes in the activity of the intestinal mucosal mast cells (IMMC) in multiple organ failure (MOF). METHODS: A rat model of MOF was induced by intraperitoneal injection of zymosan. Both the functional alterations and the pathological morphology of essential organs, such as small intestine, liver, kidney and the lungs, were evaluated. The concentrations of histamine and tumor necrosis factor alpha (TNF-alpha) in plasma and small intestinal tissue were detected by fluorimetric assay and enzyme-linked immunosorbent assay, respectively. The ultrastructural changes of the IMMC from the MOF rats were evaluated by transmission electron microscopy. RESULTS: Zymosan induced obvious inflammatory morphology and functional impairment in the essential organs of the rats that were indicative of the characteristic changes in MOF. There was a significantly decreased concentration of histamine in the intestinal tissue of the MOF rats when compared with the normal controls (8.67 +/- 1.16 vs 11.63 +/- 1.97 ng/g protein, P < 0.01), whereas the plasma histamine concentration showed no significant changes. The concentration of TNF-alpha was elevated significantly in both the intestinal tissue and plasma of MOF rats. Furthermore, both the increased number and level of degranulation of the IMMC in the gut tissue was marked in MOF rats. CONCLUSION: The results suggest that the histamine and TNF-alpha released from activated IMMC play an important role in the development of MOF.

Animals↗

PubMed1992

[Multiple organ failure following severe acute pancreatitis: its clinically patterns and pathogenetic factors].

To detect the clinical course and possible pathogenetic factors of multiple organ failure (MOF) after severe acute pancreatitis (SAP), we investigated retrospectively 70 consecutive patients with SAP for a 16-year period. Two different patterns of MOF were identified: rapid-single phase MOF developed early after SAP attack, and delayed tow-phase MOF developed progressively and sequentially with a lag phase. The clinical course of MOF was characterized by a severely systemic inflammatory response. Clinical variables associated with the evolution of MOF included early circulatory shock, pancreatic sepsis and severe pancreatic necrosis, which might be the leading one. It is suggested that the generalized inflammatory response triggered by the toxic focus seems to be the final common pathway linking SAP with MOF syndrome.

Abscess↗

PubMed1990

[An analysis of DIC in patients with multiple organ failure--variations of the molecular makers and its clinical usefulness].

We studied blood coagulation and fibrinolysis in 18 DIC patients with multiple organ failure. Blood was collected three times (1st, 3rd, 6th hospital days) from an indwelling arterial line, and FPA, FPB beta 15-42, alpha 2PI-P1-C, D-dimer, t-PA; Ag, and t-PA activity were measured. 1) Continuous FOY infusion (1.40 +/- 0.07 mg/kg/H) resulted in a statistically significant fall of FPA levels, which however, was still above normal. The FPA levels of the patients whose DIC score was not improved or who had massive hematomas were statistically higher than the patients whose DIC score was improved or without hematomas. 2) FPB beta 15-42, alpha 2PI-Pl-C, and D-dimer remained at consistently high levels following onset of the DIC. A significant positive correlations were seen between these indices; between the FPA and FPB beta 15-42, alpha 2PI-Pl-C. 3) The levels of alpha 2PI-Pl-C were found to be higher in the patients with hematomas than those without hematomas. 4) T-PA; Ag level remained at consistently high during all hospital day. On the other hand, t-PA activity level did not change significantly. There was dissociation between the t-PA; Ag and the t-PA activity. 5) The patients whose DIC score were not improved on the 6th hospital day had higher levels of t-PA; Ag than the patients whose DIC score were improved, but there were no differences in the number of the ischemic organs between these patients. In conclusion, regardless of the continuous FOY infusion some patients revealed the continuous production of thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2002

Multiple organ failure in patients with cardiogenic shock is associated with high plasma levels of interleukin-6.

OBJECTIVE: In patients with septic shock, multiple organ failure (MOF) is associated with high levels of interleukin-6 (IL-6). Although organ failure is also a common complication of cardiogenic shock (CS), IL-6 levels have been reported to be lower in patients with CS than in patients with septic shock. We studied IL-6 plasma levels in patients with CS with respect to organ failure. SETTING: Eight-bed intensive care unit at a university hospital. PATIENTS: Fifty-one patients with CS, 26 patients with septic shock, and 11 noncritically ill controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with CS had higher IL-6 levels than noncritically ill controls ( p<.001) but lower levels than patients with septic shock ( p=.003). CS patients with MOF at the time of blood sampling exhibited, however, higher IL-6 levels than CS patients without organ failure, and IL-6 levels in patients with CS correlated to the total Sepsis-related Organ Failure Assessment score at the time of blood sampling ( r=.57, <.001). No significant differences in IL-6 levels were found when comparing CS patients with MOF at the time of blood sampling with patients with septic shock. Furthermore, CS patients who developed MOF during ICU stay exhibited significantly higher IL-6 levels than CS patients who never did develop MOF. An IL-6 level of >200 pg/mL had a 93% specificity and 100% sensitivity for the prediction of MOF in patients with CS. CONCLUSIONS: Once MOF is present, patients with CS exhibit similarly high IL-6 levels as patients with septic shock. High IL-6 levels in CS patients are associated with a progression to MOF.

Aged↗

PubMed2000

Relationship between plasma cytokine concentration and multiple organ failure in patients with acute pancreatitis.

The dynamic aspects of circulating cytokines and cytokine modulators and their relationship with development of multiple organ failure (MOF) in patients with acute pancreatitis were analyzed. All cytokine and C-reactive protein levels in the circulation were higher than those in the MOF group. In particular, plasma concentrations of soluble tumor necrosis factor receptors (sTNF-RI and sTNF-RII) were significantly higher in patients with MOF than in those without even at admission. Furthermore, plasma concentrations of sTNF-Rs and interleukin-1 (IL-1) receptor antagonist (IL-1ra) were much higher than those of their counterparts, TNFalpha and IL-beta, respectively. These results suggest that the plasma concentrations of sTNF-Rs are useful predictors for the development of MOF, and actions of TNF-alpha and IL-1beta could be regulated by their modulators (soluble receptor and receptor antagonist, respectively) in the pathologic condition of severe acute pancreatitis.

Acute Disease↗