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

The metabolic alterations, nutritional and metabolic assessment, and nutritional requirements of critically ill patients are discussed, and parenteral nutrition support therapies are reviewed. Physiological alterations in the metabolism of the injured or septic patient are mediated through the interactions of neuroendocrine, cardiovascular, toxic, and starvation responses. These responses cause mobilization of nutritional substrates in an effort to maintain vital organ function and immune defenses. A patient's nutritional status can be determined from anthropometric measurements, creatinine excretion rate, and evaluations of protein stores and immune reserves and function; body weight is a poor indicator. Nitrogen-balance calculations are also useful for determining the adequacy of nutritional intake and the degree of metabolic stress. Early assessments of nutritional status may assist in identifying those patients for whom nutritional support interventions are needed. Nutritional requirements are altered by the metabolic responses to injury and sepsis. Studies suggest that use of nutrient solutions enriched for branched-chain amino acids may enhance nitrogen retention and that energy expenditures in injured or septic patients are only moderately elevated. Most nonprotein calories in parenteral nutrient solutions are provided as glucose, but lipids are an important source of energy in the critically ill patient who has high energy requirements or carbohydrate intolerance; however, clearance of lipids may be decreased. Fluid, electrolyte, and mineral status must be evaluated frequently. Critically ill patients have unique nutritional requirements, and parenteral nutrition support therapies for these patients are being investigated and refined.
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PMID:Parenteral nutrition in the critically ill patient. 250 29

Recently a relationship has been postulated between lowered intracellular glutamine concentrations in the skeletal muscle and the rate of protein synthesis. We investigated the effect of 48 hours of parenteral nutrition supplemented with a solution containing glutamine in free or dipeptide form (alanylglutamine or glycylglutamine) on the intracellular glutamine pool in skeletal muscle and on the hind limb exchange of glutamine in dogs with sepsis after surgery. Before surgery, dogs were fasted for 48 hours. We used glutamine dipeptides as sources because they remain stable in an aqueous solution. Nutrition solutions were isocaloric (17.8 kcal/kg body weight/day on day 1 and 35.6 kcal/kg on day 2) and isonitrogenous (0.33 gm nitrogen/kg body weight/day), providing 2.6 mmol/kg body weight/day as glutamine source. During starvation, muscular free glutamine levels decreased by 41% to 10.4 mmol/L (p less than 0.001). On the second postoperative day the dogs had lowered plasma protein levels, a sharp drop in platelet count, an increase in the leukocyte count, and positive blood cultures. None of the solutions investigated in this study was effective in repleting the glutamine pool during 2 days of postoperative nutrition (11 +/- 2.0 mmol/L without glutamine, 10.3 +/- 2.2 mmol/L with glutamine plus alanine, 9.9 +/- 1.6 mmol/L with alanylglutamine, 7.5 +/- 1.1 mmol/L with glutamine plus glycine, and 7.2 +/- 1.2 mmol/L with glycylglutamine, respectively). The release of glutamine from the hindquarter was 631 +/- 38 nmol/kg body weight/min in the control group and decreased significantly in dogs receiving alanylglutamine (13.5 +/- 45 nmol/kg body weight/min; p less than 0.001) or the constituent amino acids (265 +/- 66 nmol/kg body weight/min; p less than 0.01) but was unchanged in dogs receiving glycylglutamine or glutamine plus glycine. We conclude that the duration and dosage of glutamine administration (equivalent to 26 gm glutamine per day in a patient weighing 70 kg) used in this study are not sufficient to restore glutamine deficiency of the skeletal muscle in the depleted state.
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PMID:Glutamine-containing dipeptides as infusion substrates in the septic state. 251 Mar 34

The effect of administered human growth hormone (hGH) on protein metabolism in septic rats was investigated. Fifty-three male Wistar rates with SVC cannulation were divided into four groups. Group I (n = 10) underwent sham-operation. Sepsis was induced by cecal ligation in group II (n = 19), group III (n = 10), and group IV (n = 14). Isocaloric, isonitrogenous glucose/amino acids were infused for 4 days. hGH was administered in group III (100 mU/day) and group IV (200 mU/day) every day. Cumulative nitrogen balance (mg/kg) in group IV was significantly higher than in group II (p less than 0.01): group I, 1264 +/- 355; group II, 117 +/- 693; group III, 92 +/- 735; group IV, 1001 +/- 279. Cumulative urinary excretion of 3-methylhistidine (3-MH, mg/kg) did not differ between group II and group IV: group I, 6.2 +/- 0.9; group II, 12.0 +/- 2.2; group III, 13.4 +/- 2.9; group IV, 10.5 +/- 2.3. Serum albumin level in group IV (1.8 +/- 0.2 g/dl) was significantly higher than in group II (1.5 +/- 0.2 g/dl) (p less than 0.01). Blood urea nitrogen level in group IV (12.6 +/- 2.3 mg/dl) was significantly lower than in group II (18.8 +/- 7.4 mg/dl) (p less than 0.05). Although serum levels of glucose, insulin, triglyceride, and phospholipid were higher in sepsis groups than in sham-operated group, those levels did not differ among sepsis groups. Administration of hGH, 200 mU/day, resulted in marked nitrogen retention and had little effect on 3-MH excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of administered human growth hormone on protein metabolism in septic rats. 251 84

To evaluate the effect of tumor necrosis factor (TNF), a major mediator of sepsis, on lung structure and function, we infused 200-g male Wistar rats with TNF (0, 2 x 10(5), or 4 x 10(5) U/kg of TNF) for 24 hours. Volume-pressure measurements were determined in the excised lungs using both air and saline, which eliminated surface tension forces. Total lung wet and dry weight, nitrogen level, and DNA and protein content were measured. Lungs of the rats that received TNF accepted significantly smaller volumes of air and saline at all pressures compared with the control group. Both the lung wet and dry weights increased with TNF. Lung DNA and protein content also increased, suggesting increased cellularity in the TNF-infused lungs. Thus, the lungs of the TNF-treated rats were stiffer, with reduced compliance values, and heavier due to increased water content and increased cellularity. These data indicate that sublethal administration of TNF in this rat model induces the adult respiratory distress syndrome and increases the work potential of respiration.
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PMID:Tumor necrosis factor induces adult respiratory distress syndrome in rats. 258 64

Activated macrophages convert L-arginine to citrulline and unstable nitrogen oxides that have cytotoxic properties. We recently have shown that the inhibition of protein synthesis in Kupffer cell (KC):hepatocyte (HC) coculture, following exposure to gram-negative bacterial endotoxin (lipopolysaccharide), is due to the metabolism of L-arginine by this cytotoxic pathway. Although this finding supports a role for activated KCs and the L-arginine-dependent mechanism in the HC dysfunction seen in sepsis, it and previous studies have failed to demonstrate direct damage to HCs by adjacent KCs. The current study was undertaken to determine if KCs exposed to lipopolysaccharide could directly damage HCs and, if so, whether the damage was dependent on the metabolism of L-arginine. By using the release of aspartate aminotransferase as a marker of HC damage, it was found that a significant aspartate aminotransferase release by KC:HC cocultures in response to lipopolysaccharide occurred only if L-arginine was present. In addition, requirements for significant aspartate aminotransferase release included KC:HC ratios of 7.5:1 or greater and L-arginine concentrations of 1 mmol or more. Although the KC-induced damage was mild, these results show that in vitro HC damage in KC:HC coculture does require the metabolism of L-arginine and supports a hypothesis that toxic L-arginine metabolites may contribute to liver cell damage in patients with sepsis.
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PMID:Kupffer cell cytotoxicity to hepatocytes in coculture requires L-arginine. 258 66

Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats. It is not known if the response to sepsis is similar in young and adult rats. This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP. In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP. Levels of glycogen in liver and muscle were determined 16 hours after CLP. Mortality rate was similar in young and adult rats. MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats. HR was higher in young rats at all times studied. The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours. Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis. Both young and adult rats became hypoaminoacidemic after CLP. The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups. REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and metabolic alterations during experimental sepsis in young and adult rats. 291 92

The hepatic failure associated with severe sepsis is characterized by specific, progressive, and often irreversible defects in hepatocellular metabolism (1). Although the etiologic microbe can often be identified, the direct causes and mechanisms of the hepatocellular dysfunction are poorly understood. We have hypothesized that Kupffer cells (KC), which interact with ambient septic stimuli, respond by providing signals to adjacent hepatocytes (HC) in sepsis . Furthermore, we have provided evidence (2, 3) that KC activated by LPS from Gram-negative bacteria can induce profound changes in the function of neighboring HC in coculture. In our model, coculture of either KC (2) or peritoneal macrophages (Mphi)(3) with HC normally promotes HC protein synthesis ([(3)H]leucine incorporation). The addition of LPS or killed Escherichia colt' to such cocultures induces a profound decrease in HC protein synthesis, as well as qualitative changes ([(35)S]methionine, SDS-gel electrophoresis) in protein synthesis without inducing HC death (2, 3) . In this report we show that the inhibition in protein synthesis is mediated via an L-arginine-dependent mechanism. The metabolism of L-arginine by activated Mphi to substances with cytostatic and even lethal effects on target cells is a relatively recent discovery. After the description by Stuehr and Marletta (4, 5) that LPS- triggered Mphi produced nitrite/nitrate (NO(2)(-)/NO(3)(-)), Hibbs et al. (6, 7) and Iyengar et al. (8) demonstrated that L-arginine was the substrate for the formation of both these nitrogen end products and citrulline. A role for the arginine-dependent mechanism in Mphi tumor cytotoxicity (6, 7) and microbiostatic activity (9) has been suggested. However, the in vivo functions of this novel Mphi mechanism have not yet been defined, but it is possible that there are both physiologic as well as pathologic roles. Our in vitro results raise the possibility that some metabolic responses to microbial invasion maybe partially mediated by the L-arginine-dependent mechanism. What other metabolic responses are affected and the possible pathologic consequences remain to be studied.
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PMID:An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. 292 30

Medium-chain triglycerides (MCTs) and medium-chain fatty acids (MCFAs) have special physicochemical properties such as small molecular weight, small interfacial tension against water, and for the fatty acids, solubility in biological fluids. As a result the metabolic pathways followed by these fats in an organism are different and simpler, or identical but more rapid, than those followed by long-chain triglycerides (LCTs) and long-chain fatty acids (LCFAs). Consequently the MCTs have found numerous applications in oral or enteral nutrition and, more recently, in parenteral nutrition. The infusion of conventional fat emulsions in stress and sepsis is still controversial. A main question is whether an MCT supply can be beneficial for these patients. In this review, we will discuss different aspects of modified lipid and protein metabolism: exchanges between exogenous fat particles and lipoproteins; exogenous fat clearance, storage, and oxidation; reticuloendothelial system function; nitrogen balance; and hepatic function. For each of these perturbations, the MCT/LCT and structured lipid emulsions are theoretically capable to provide an appropriate solution. The efficiency of these emulsions has been demonstrated experimentally on animal models of stress and sepsis. However, the value of MCT-based fat emulsions for these pathological states has still to be ascertained by clinical studies.
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PMID:Medium-chain triglyceride-based fat emulsions: an alternative energy supply in stress and sepsis. 306 44

A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.
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PMID:Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial. 307 94

Between March 1982 and September 1983, 40 inpatients (25 men and 15 women, mean age 53 years) with alcoholic cirrhosis and total serum bilirubin greater than or equal to 5 mg per dl were studied. Those with hepatocellular carcinoma, renal failure, hyponatremia, septicemia, spontaneous bacterial peritonitis, gastrointestinal bleeding, and hepatic coma were excluded. Patients were studied for 28 days. The two groups were offered an oral diet containing 40 kcal per kg per day. Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter. The major endpoint was total serum bilirubin on Day 28. On admission, serum bilirubin was not significantly different in the two groups: oral group, 12.5 +/- 6.6 mg per dl; supplementary parenteral nutrition group, 12.3 +/- 8.5 mg per dl. On Day 28, serum bilirubin was lower in the supplementary parenteral nutrition group (2.5 +/- 1.4 mg per dl) than in the oral group (4.1 +/- 2.2 mg per dl) (p less than 0.02). Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7, 14 and 21 (p less than 0.05). Analysis of covariance, considering serum bilirubin on admission and at randomization and time between admission and randomization, confirmed these results. On Day 28, anthropometric parameters, serum transferrin, prealbumin and retinol-binding protein were higher in the supplementary parenteral nutrition group, but the differences were not significant. Serum albumin was significantly lower in the supplementary parenteral nutrition group. The incidence of encephalopathy and sepsis was not significantly different between the two groups.
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PMID:A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients. 308 33


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