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Pathophysiology, Circumstances of occurrence of SIRS, the MODS and MOF

Situations leading to the existence of an uncontrolled SIR, MODS or MOF is many. These are situations willingly "surgical," such as trauma, burns, acute pancreatitis or situations more avidly treated in medical ICUs such as infectious pneumonia, whatever its nature, sepsis and severe infections, septicemia, pneumonia inhalations. If during the first descriptions, multiple organ failure, was readily linked to infections, it currently seems possible to describe the table above in situations where the infection does not play a fundamental role (especially in trauma cases or pancreatitis). The pathophysiology of MODS is now based on knowledge gained over the last 5 to 10 years of inflammation. Multiple organ failure is a systemic inflammatory process uncontrolled reaction to aggression whatsoever. This process involves the whole body and each organ.

The inflammatory mediators involved in this situation are very numerous, are described in more than 60 currently. In recent years, multiple studies have clearly demonstrated the role of both local and systemic mediators. Such is the case of cytokines: TNF, interleukin 1, interleukin 6, interleukin 8, PAF. These molecules can promote the inflammatory response, both at the systemic and local levels. At the local level by allowing, in the expression of adhesion molecules, the interaction between endothelial cells and circulating blood cells: platelets and coagulation activation, leukocytes and activation of chemistry granulocytic behind the production of free radicals of oxygen. At the systemic level, these molecules can activate several cellular targets locally first are the macrophage system that can auto-active "cascade."

All clinical trials, usually grouped under the term "immunotherapy of sepsis," were intended to neutralize or modulate the biological effects of these mediators, whether of anti cytokine or anti-oxidants or the last endogenous mediator: NO.

Besides the mediators, the intestine appears to play a fundamental role in the maintenance and perpetuation of inflammation at the origin of MODS and multiple organ failure. Freshly, Vallet et al have clearly shown the deleterious effect of perfusion abnormalities or ischemia-reperfusion phenomena in the mucosa and submucosa of the bowel, when situations such as shock assault septic, hypovolemic shock, trauma or burn. Under these conditions, the intestinal bacteria that colonized the intestine may pass into the lymphatic and blood circulation making the phenomenon of "bacterial translocation," now formally demonstrated in several animal models and recently even in humans. Bacteria can be found in the mesenteric lymph, liver and spleen. Under such conditions, the release of bacteria and antigens such as endotoxins or exotoxins into the bloodstream or the lymph, is likely to maintain stimulation and secretion of pro-inflammatory mediators. The liver, which represents a significant barrier to these phenomena, due to the presence of the macrophage system consists of Kupffer cells (70% of the macrophage in the body sit in the liver) has the capacity to modulate and counteract this bacterial translocation, but when liver dysfunction appears, this ability appears to decrease. The pro-inflammatory cascade, bacterial translocation, the regional anomalies and / or visceral perfusion, impaired tissue extractions of oxygen are a set pathophysiological self-activating whose resultant is a growing expectation of each org donkey defining multiple organ failure.

pathophysiology of diabetes mellitus

As in many other situations in medicine, prevention, rather than therapeutic care, SIRS or MODS of the MOF is preferable. Some fundamentals must be observed: rapid response and appropriate shock, preoperative assessment when this is feasible risk peri-and postoperative. Intraoperative monitoring of renal hemodynamic and acid-base functions, prevention of nosocomial infections and early postoperative peri, especially in patients at risk, that is to say, diabetes, immunocompromised or receiving corticosteroids. Close monitoring of respiratory function, prevention of atelectasis, pulmonary nosocomial infection control, prevention of aspiration pneumonia, adaptation and regulation of thin and narrow terms of ventilation, to prevent barotrauma and volutrauma. Digestive decontamination seems to be part of these preventive measures. It usually involves oral administration of antibiotics: tobramycin, polymixin, antifungal and sometimes vancomycin. However, prospective evaluation of this method has not shown a major role on mortality. This statement should be qualified overall; it seems that digestive decontamination can reduce the incidence of nosocomial pneumonia, certain subgroups of multicenter studies, involving a large and heterogeneous population of patients seem to benefit from such a technique, in particularly those suffering from trauma. Even though, to date, it seems difficult to reach consensus on the real interest of digestive decontamination in mechanically ventilated patients. Gastine et al clearly demonstrate the lack of interest in terms of morbidity and mortality of this technique in patients in intensive care. More than this technique, careful monitoring perioperative and postoperative determination of risk factors, the conditioning optimal preoperative patients, reduction of immunosuppression factors seemed to be the most effective prevention.

Treatment should be the correction point by point the pathophysiological mechanisms at the origin of SIRS and MODS. In this sense, several chapters deserve to be studied: hemodynamic monitoring to optimize the transport of oxygen to tissues, control of sources of infections, metabolic media are the main modes of treatment of SIRS MODS or MOF. Optimization of oxygen transport is probably desirable, but it should not be accompanied by an excess of investment dependence as therapeutic oxygen consumption-oxygen transfer does not seem to represent the fundamental regulating the therapeutic. The main purpose is to ensure the delivery of oxygen, needed by the body, by increasing cardiac output, maintaining the number of hemoglobin above 10 g · 100 mL -1, maintaining a saturation arterial oxygen> 90% to meet the metabolic demand of the different viscera.

However, there is now unrealistic about specific optimize the delivery of oxygen to each organ, being unable to control the regional variations in traffic. The best outcome of the optimization of oxygen transfer probably depends even today on the assessment and development of blood lactate due to the mathematical relationship to the relationship. Calculated, it is hardly possible the present to rely on it to optimize treatment. Under these conditions, it seems necessary to proceed step by step, by increasing cardiac output by altering preload, afterload reduction, myocardial contractility by positive inotropic drugs, for the correction of anemia and the preservation of arterial oxygen saturation. These steps follow gradually, the evolution of the hyperkinetic syndrome usually encountered in these situations and to monitor treatment effects on parameters such as PaO 2 / FIO 2, serum creatinine, blood lactate, diuresis.

When the optimization of oxygen transport is performed, metabolic support should be made. The goal is to get a balance between catabolic and nutritional intake. Excessive intake of calories appears to be relatively deleterious. Carbohydrates should probably not exceed 5 g · kg -1 per day because of the risk of hepatic lipogenesis, excess production of CO 2 when this amount is exceeded. The intake of long chain fatty acids should not exceed 1 g · kg -1 per day. The administration of protein should be between 1.5 and 2 g · kg -1 per day. The use of preparations with high concentrations of amino acids to branched-chain appears to be effective in limiting the catabolism of the body. These formulas are particularly recommended in patients that eliminate over 10 g of nitrogen per day. The use of liquid-rich oil source of "fish," containing polyunsaturated fatty acids "omega-3," appear to reduce the production of prostaglandins and leukotrienes widely produced in situations of MODS. It seems that the system is to reduce the release of interleukin 1 and TNF. Fatty acids "omega-3," arginine and certain nucleotides were introduced into special formulas for enteral nutrition to provide nutritional support for situation's qualitative hyper metabolic of MODS. Very recent work appears to have shown clinical efficacy of these regimes (reduction of nosocomial infections, shorter stay inpatient intensive care unit) Nutritional support, both qualitatively and quantitatively, seems fundamental in the therapeutic management of MODS and MOF, not least from the standpoint immunological, protein intake to prevent the relative immune suppression observed during these situations. Where possible, food should always be practiced enteral: indeed, it allows, failing to provide the caloric amount sufficient to reduce the occurrence of infectious complications of parenteral nutrition. The diet should be started as soon as possible, that is to say, one or two days after the attack in the absence of cons-indication of surgical nature.

All nutritional formulas, including elements to increase immune function will be preferred. Indeed, recent studies show that these formulas shorten the stay of patients in intensive care unit. However, no support metabolic has so far proven to improve survival of patients with SIRS, MODS or MOF. Outside of respiratory support, assistance kidneys, hemofiltration, hemodialysis, hemodynamic monitoring and supports earlier metabolic, no specific therapy currently appears to provide an improvement in survival. It should, in contrast, day after day, to check if an infectious etiology is not responsible for the perpetuation of this state (e.g. drain an abscess, excision of an infected skin wound, verify the absence of pulmonary infection site, urine or other).

In situations of trauma, stabilization of fractures performed as quickly as possible seems to improve prognosis, since it allows early mobilization. In the presence of burns, excision of burned areas, and the rapid implementation of skin grafts are all therapeutic maneuvers to minimize the effects of tissue injury. Until now, new therapies and immunotherapy, in particular, have not proven their effectiveness in these situations. The introduction of monoclonal anti-endotoxin or anti-mediators (TNF, anti-PAF anti-IL1ra) have not proven their effectiveness. Other avenues of approach are being explored, inhibition or modulation of expression of adhesion proteins, using anti-inflammatory cytokines such as IL4 and IL10. The use of antioxidants to reduce the toxicity of metabolites of oxygen (catalase, vitamin E) have been the very limited success not allowing to formal advice. However, the safety, for example, vitamin E, appears to allow its use in the initial stages of acute lung injury. Prevention of nosocomial infections in these situations, hand washing, by a duly completed antibiotic policy in the intensive care unit, through the use of disposable equipment seem to be accountable for the prevention and treatment of these situations.

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