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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite implementation of CDC recommendations and bundled interventions for preventing catheter-associated blood stream infection, ventilator-associated pneumonia, or urinary catheter-associated infections, nosocomial infections and sepsis remain a significant cause of morbidity and mortality in critically ill children. Recent studies suggest that acquired critical illness stress-induced immune suppression (CRISIS) plays a role in the development of nosocomial infection and sepsis. This condition can be related to inadequate zinc, selenium, and glutamine levels, as well as hypoprolactinemia, leading to stress-induced lymphopenia, a predominant T(H)2 monocyte/macrophage state, and subsequent immune suppression. Prolonged immune dysfunction increases the likelihood of nosocomial infections associated with invasive devices. Although strategies to prevent common complications of critical illness are routinely employed (eg, prophylaxis for gastrointestinal bleeding, thrombophlebitis), no prophylactic strategy is used to prevent stress-induced immune suppression. This is the authors' rationale for the pediatric CRISIS prevention trial (NCT00395161), designed as a randomized, double-blind, controlled clinical investigation to determine if daily enteral supplementation with zinc, selenium, and glutamine as well as parenteral metoclopramide (a dopamine 2 receptor antagonist that reverses hypoprolactinemia) prolongs the time until onset of nosocomial infection or sepsis in critically ill children compared to enteral supplementation with whey protein. If effective, this combined nutritional and pharmacologic approach may lessen the excess morbidity and mortality as well as resource utilization associated with nosocomial infections and sepsis in this population. The authors present the design and analytic plan for the CRISIS prevention trial.
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PMID:Rationale and design of the pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial. 1940 4

The essential trace element selenium (Se), in the form of selenoproteins, plays a pivotal role in the antioxidant defense system of the cell. There is evidence that Se may confer benefits in patients with inflammatory disease and even infectious diseases like HIV. Furthermore, in patients with severe sepsis, characterized by an increase in reactive oxygen species and low endogenous anti-oxidative capacity, as well as in patients with systemic inflammatory response syndrome, Se supplementation may reduce mortality and improve the clinical outcome, respectively. The nuclear factor kappa-B (NF-kappaB) signaling pathway has been associated with enhanced inflammatory response and its activation has been significantly correlated with interleukin-6 and TNF-alpha production. Selenium may inhibit the activation of NF-kappaB by modulating selenoprotein genes expression. Moreover, Se supplementation in chronic inflammation restores the depleted hepatic and serum Se levels by increasing selenoprotein biosynthesis leading to suppressed CRP production thereby attenuating the inflammatory process. Se increases shedding of L-selectin from monocytes while decreasing soluble L-selectin, which has been reported to be associated with high mortality in patients with sepsis. These mechanisms are likely to contribute to the modulatory effects of an increased Se status on the inflammatory response. This review evaluates some apparently key mechanisms of the anti-inflammatory action of selenium and advocates Se supplementation as a modulator of inflammatory response in infectious and autoimmune disease. Prospective, randomized, controlled studies must be performed to provide a greater degree of certainty.
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PMID:Selenium and inflammation: underlying anti-inflammatory mechanisms. 1941 16

Administration of sodium selenite in septic shock has been associated with apparently conflicting results that may be related to different dosing schedules. Bolus administration, leading to a transient pro-oxidative effect, could limit the inflammatory reaction and improve outcomes. We studied 21 anesthetized, mechanically ventilated, invasively monitored, and fluid-resuscitated sheep. Nine hours after inducing peritonitis by injection of autologous feces, the animals were randomized into three groups: (i) bolus injection (2 mg selenium as selenite, followed by 0.06 microg . kg-1 . h-1, n = 7); (ii) continuous infusion (4 microg . kg-1 . h-1 selenium, n = 7), or (iii) control (n = 7). No vasopressors or antibiotics were administered. All animals were monitored until spontaneous death. Peak plasma selenium values reached 4 to 14 micromol . L-1. Compared with the other groups, sheep given a bolus of sodium selenite had delayed hypotension with better maintained cardiac index, delayed hyperlactatemia, fewer sepsis-induced microvascular alterations, and a prolonged survival time (21.9 [bolus group] vs. 18.4 [continuous group] and 18.3 h [control group], P < 0.05). Hence, in this model of septic shock, the administration of a large bolus of sodium selenite (rather than a continuous administration) resulted in beneficial effects, probably by a transient oxidative effect.
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PMID:A large-bolus injection, but not continuous infusion of sodium selenite improves outcome in peritonitis. 2040 54

Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. Recent studies pointed out the correlations between oxidative stress, systemic inflammatory response and apoptosis. Prospective randomized clinical trials regarding antioxidant therapy in critical illness provide increasing evidence in support of selenium, glutamine and omega-3 fatty acids. In particular selenium seems to improve clinical outcome in terms of infections and organ failure, glutamine has been associated with a significant reduction in infectious complications and omega-3 fatty acids could be particularly efficacious in sepsis. Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.
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PMID:Antioxidant therapy in critically septic patients. 1979 41

Selenium (Se) is an essential nutrient for human beings, with serious consequences resulting from clinical deficiency. It therefore should be provided intravenously to all patients who require parenteral nutrition (PN). Moreover, because the effects of suboptimal status are variable and unclear, this supplementation should be provided from the beginning of the course of PN. In most patients receiving PN at home or after surgery, 60-100 mcg/day will meet their requirements. Patients who commence PN already depleted in selenium may require more. Critically ill patients or those with severe burns may have higher requirements. There is good evidence that up to 400 mcg/day is beneficial in burn patients, but the evidence is inconclusive regarding the benefit of high-dose selenium in severe sepsis. Where increased Se provision is used, or in long-term PN, selenium status should be monitored by measurement of plasma Se together with a measure of systemic inflammatory response syndrome, such as C-reactive protein. There are many research issues, including which biochemical measurements best reflect tissue function, especially immune function in seriously ill patients, the clinical consequences of suboptimal biochemical Se status, whether high-dose Se improves outcome in critically ill patients, and whether extra Se always should be given with extra intakes of other antioxidants.
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PMID:Selenium in intravenous nutrition. 1987 51

Patients with parenteral nutrition depend on an adequate supply of micronutrients, in particular, antioxidant vitamins and cofactors such as selenium. In cases of oxidative stress (eg, chronic inflammation, sepsis, lung distress syndrome, and organ failure), there is a higher need for antioxidants. One of the most important antioxidant vitamins is vitamin E. For very low birth weight infants the plasma level is an indicator for adequate supply and for safety. Safe and effective blood levels are between 23 and 46 micromol/L, maintained with a dose of 2.8 IU/kg body weight (1-2 mg/day). For safety reasons a plasma level of 80 micromol/L should not be exceeded. For adults, 10 IU/day (9.1 mg/day) are recommended. Whether this dose is sufficient to ensure body stores and sufficient antioxidant activity is controversial. If parenteral lipid emulsions are supplied there is an additional need for vitamin E to protect the lipids (polyunsaturated fatty acids) from lipid peroxidation and to deliver additional vitamin E. Dietary guidelines for healthy adults recommend an intake of polyunsaturated fatty acids equal to 10% of total energy and an intake of alpha-tocopherol greater than 0.4 mg/g of polyunsaturated fatty acids. Randomized clinical trials are performed using special formulations of vitamin E solutions because vitamin E is available only in lipid emulsions to protect lipids, but not in an isolated solution for parenteral supply.
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PMID:Vitamin E requirements in parenteral nutrition. 1987 55

Because of inadequate sample sizes of randomized controlled trials, few immunologic interventions to treat or prevent neonatal sepsis have been reliably evaluated. International collaboration is essential in achieving timely, adequate samples to assess effects on mortality or disability-free survival reliably. Promising or possible therapeutic interventions in severe or gram-negative sepsis include exchange transfusions, pentoxifylline, and IgM-enriched intravenous immunoglobulin. Promising or possible prophylactic interventions include lactoferrin, with or without a probiotic; selenium; early curtailment of antibiotics after sterile cultures; breast milk; and earlier initiation of colostrum in high risk preterm infants. Prophylactic oral probiotics are safe and effective (P<.00001) in reducing all-cause mortality and necrotizing enterocolitis in preterm infants by over half, but do not reduce sepsis.
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PMID:Adjunctive immunologic interventions in neonatal sepsis. 2056 18

Micronutrients are defined as those compounds necessary for the adequate physiological status of the organism and that may be administered through the daily diet either enteral or parenteral. The term micronutrient encompasses the vitamins and oligoelements, also termed trace elements. Vitamins cannot be synthesized by the organism and are categorized in two groups: water-soluble vitamins (the vitamin B group, C, folic acid, and biotin) and lipid-soluble vitamins (A, D, E, and K). Oligoelements are found in small amounts in the human body, and copper, cobalt, chrome, iron, iodine, manganese, molybdenum, nickel, selenium, and zinc are considered to be essential. The important role of micronutrients in critically-ill patients has been demonstrated, and their influence on the immune system, cancer, burnt, septic, and poly-traumatized patients has extensively been put in evidence. It is important to establish the micronutrients demands for each individual in order to achieve an adequate intake. However, there is little evidence on the necessary intake to achieve proper physiological functioning under different pathologies; therefore, studies bringing light to this situation are needed. The aim of this review is to update the current state of knowledge on micronutrients supplementation in the adult population with pathologies such as cancer, coronary and cardiovascular disease, bowel inflammatory disease, short-bowel syndrome, cystic fibrosis, liver disease, renal failure, respiratory failure, the surgical patient, big-burnt patient, pancreatitis, poly-traumatized patients, sepsis and HIV. After the bibliographical search, we describe the current state of knowledge regarding micronutrients intake in artificial nutrition under the above-mentioned pathologies.
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PMID:[Advances in the knowledge of the use of micronutrients in artificial nutrition]. 2151 28

Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in some cases. In this comprehensive article, the roles of Se and individual selenoproteins in regulating immune cell signaling and function are discussed. Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells. Data obtained from cell culture and animal models are reviewed and compared with those involving human physiology and pathophysiology, including the effects of Se levels on inflammatory or immune-related diseases including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders. Finally, the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders are discussed.
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PMID:The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. 2195 27

Nutritional metabolic management, together with other treatment and support measures used, is one of the mainstays of the treatment of septic patients. Nutritional support should be started early, after initial life support measures, to avoid the consequences of malnutrition, to provide adequate nutritional intake and to prevent the development of secondary complications such as superinfection or multiorgan failure. As in other critically-ill patients, when the enteral route cannot be used to ensure calorie-protein requirements, the association of parenteral nutrition has been shown to be safe in this subgroup of patients. Studies evaluating the effect of specific pharmaconutrients in septic patients are scarce and are insufficient to allow recommendations to be made. To date, enteral diets with a mixture of substrates with distinct pharmaconutrient properties do not seem to be superior to standard diets in altering the course of sepsis, although equally there is no evidence that these diets are harmful. There is insufficient evidence to recommend the use of glutamine in septic patients receiving parenteral nutrition. However, given the good results and absence of glutamine-related adverse effects in the various studies performed in the general population of critically-ill patients, these patients could benefit from the use of this substance. Routine use of omega-3 fatty acids cannot be recommended until further evidence has been gathered, although the use of lipid emulsions with a high omega-6 fatty acid content should be avoided. Septic patients should receive an adequate supply of essential trace elements and vitamins. Further studies are required before the use of high-dose selenium can be recommended.
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PMID:[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): patient with sepsis]. 2230 58


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