Orrawin Trocki

Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding.

This study was performed to investigate the mechanism whereby immediate enteral feeding after burn injury reduces postburn hypermetabolism and hypercatabolism. Fifty-seven burned guinea pigs (30% TBSA) were divided into three groups: A (N = 19), given 175 kcal/kg/day beginning 2 hours after burn; B (N = 20), given 175 kcal/kg/day with an initial 72-hour adaptation period; and C (N = 18), given 200 kcal/kg/day with the same adaptation period as B. Resting metabolic expenditure (RME) on PBD 13 was lowest in group A (109% of preburn level), compared with group B (144%, p < 0.001) and group C (137%, p < 0.01). On PBD 1, group A had the greatest jejunal mucosal weight and thickness (p < 0.001), and mucosal weight had negative correlations with plasma cortisol (r = 0.829, p < 0.001) and glucagon (r = 0.888, p < 0.001). Two weeks after burn, urinary vanillyl mandelic acid (VMA) excretion, plasma cortisol, and glucagon were lowest in group A (p < 0.05 to p < 0.01). These hormones also significantly correlated with RME (p < 0.01 to p < 0.001). These findings suggest that immediate postburn enteral feeding can prevent hypermetabolism via preservation of gut mucosal integrity and prevention of excessive secretion of catabolic hormones.

The effect of route of nutrient administration on the nutritional state, catabolic hormone secretion, and gut mucosal integrity after burn injury

So that the efficacy of route of nutrient administration in thermal injury could be determined, a comparison was made between immediate enteral vs parenteral feedings in burned guinea pigs. Thirty-five guinea pigs underwent both catheter gastrostomy and jugular vein catheterization. On postoperative day 8, burned animals [30% total body surface area (TBSA)] were divided into an intragastrically (ig) fed group (N = 14) and a parenterally (iv) fed group (N = 14). Animals in each group received 175 kcal/kg/day with a solution of identical nutrient value beginning 2 hr after burn. The body weight change until postburn day (PBD) 8 and the average nitrogen balance were significantly better in the ig group than in the iv group. Values were also higher for the iv group than for the ig group in the early postburn period for urinary vanillyl mandelic acid (VMA) (p less than 0.05), plasma cortisol (p less than 0.05), and plasma glucagon (p less than 0.05). Also, the iv group showed reduced mucosal weight and thickness compared to the ig group on PBD 1 (p less than 0.02). There were significant negative correlations between VMA excretion and body weight change, and between plasma cortisol and jejunal mucosal structure (thickness and weight). These findings suggest that immediate postburn enteral nutrition can provide better nutritional support than parenteral nutrition through the maintenance of gut mucosal integrity and the prevention of increased secretion of catabolic hormones.

The importance of lipid type in the diet after burn injury

: The effects of different types of dietary lipids were tested in burned guinea pigs. All diets were identical except for the type of lipid, with total energy intake from lipids equaling 10%. All animals received a 30% total body surface area (TBSA) flame burn and were fed identically by pump-controlled gastrostomy feedings for 14 days. When compared to safflower oil (74% linoleic acid) as well as linoleic acid alone, fish oil (18% eicosapentaenoic acid or EPA) administration resulted in less weight loss, better skeletal muscle mass, lower resting metabolic expenditure, better cell mediated immune responses, better opsonic indices, higher splenic weight, lower adrenal weight, higher serum transferrin, and lower serum C3 levels. With the exception of better cell mediated immune responses in the animals fed linoleic acid, the administration of indomethacin made little difference. These findings can be explained by a reduction in the synthesis of the dienoic prostaglandins that are derived from the omega 6 series of fatty acids, some of which are significantly immunosuppressive. Regulation of dietary lipids may be an important therapeutic advance in nutritional support after burn injury, and controlled trials should be considered.

Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals.

This study describes and analyzes sequential changes in plasma and skeletal muscle free amino acids following severe burn injury. Plasma free amino acids were determined in children (n = 9) with burns averaging 60% total body surface area and were compared with laboratory beagles (n = 44) which received a flame burn totaling 30% of their body surface area. In addition, needle biopsy specimens were obtained from the semitendonosus muscle in the animals to determine free intracellular amino acids. In both patients and animals the amount of total free amino acids in plasma fell following burn, suggesting relative protein deficiency. This drop was primarily due to a 47% drop in nonessential amino acids. However, plasma phenylalanine was consistently higher than normal following burn, and was strongly associated with death and weight loss in both animals and patients, especially when analyzed as a ratio with tyrosine. This finding suggested excessive catabolism, hepatic dysfunction, or both. Plasma levels of several amino acids correlated significantly with weight loss. Alterations in muscle free amino acids generally were similar to plasma amino acids. Exceptions were muscle alanine and glycine which strongly correlated with weight loss. However, the determination of muscle free amino acid profiles did not yield clinically useful information not available from plasma profiles. Plasma levels of liver enzymes suggested progressive hepatic dysfunction. These studies show that the laboratory beagle is a good model for studying the metabolic alterations of amino acids that accompany burn injury, since they mimic humans in many parameters which appear to be most useful with respect to clinical evaluation.

Optimal Lipid Content for Enteral Diets following Thermal Injury

This study was performed to determine the effects of different amounts of lipid in enteral diets during the postburn period. Forty-five guinea pigs with catheter gastrostomy received a 30% total body surface area full thickness flame burn. After burn they were given intragastric tube feedings using five diets at different dietary lipid composition: 0, 5, 15, 30, and 50% of nonprotein calories. Total calories administered (175 kcal/kg/day), protein content and composition (20% of total calories), total volume, and vitamin and mineral content were constant in all animals. At postburn day 14, body weight, carcass weight, and muscle weight were the greatest in 0 and 5% lipid groups, and the least in 30 and 50% lipid groups. Serum transferrin was highest in the 5 and 15% lipid groups, and lowest in the 30 and 50% lipid groups. Total nitrogen content in muscle and cumulative nitrogen balance were best in the 15% lipid group. Liver fatty infiltration, caused from a larger proportion of carbohydrate administration, was greater in the 0 and 5% lipid groups and less in 15 and 30% groups. It is concluded that dietary lipid levels between 5 and 15% of nonprotein calories are optimal for nutritional support after burn injury. The nutritional management of postburn patients with higher levels of dietary lipid should be reconsidered.

Effects of fish oil on postburn metabolism and immunity

The metabolic effects and immune responses of different levels of fish oil in enteral formulas for postburn nutritional support were studied. Thirty-seven burned guinea pigs with previously placed gastrostomy feeding tubes were given diets containing 5, 15, 30, or 50% of nonprotein calories as fish oil. These diets were isonitrogenous, isocaloric, and contained identical amounts of vitamins and minerals. After 14 days of enteral feeding, there were no significant differences in resting metabolic expenditure, serum transferrin, and albumin levels. Weight loss was significantly greater in groups receiving 30 and 50% of fish oil compared to groups which received 5 and 15% of fish oil. Carcass weights and liver weights of animals in the two groups that received diets with higher lipid content were also significantly lower. Cell-mediated immunity, macrophage bactericidal indices, and opsonic indices were not different among the groups. This study confirms that diets containing lower levels of lipids are more effective for enteral nutritional support than those containing higher levels. In contrast to linoleic acid rich lipid sources, higher levels of fish oil did not show adverse effects on immunity possibly because it contained high concentrations of omega 3 fatty acids which are not precursors of immunosuppressive prostaglandin E2.

Prevention of Yeast Translocation across the Gut by a Single Enteral Feeding after Burn Injury

Recently, burn injury has been shown to facilitate the ability of enteric Candida albicans (CA) to penetrate the gut epithelium and translocate to the mesenteric lymph nodes (MLN) during the first 24 hr after injury. Guinea pigs were given 3 X 10(10) CA intragastrically before inflicting a 50% burn to determine if a single enteral feeding could affect CA translocation to the MLN. A bolus infusion (20 kcal/kg, 12 ml in volume) of liquid meal, consisting of 68% carbohydrate, 20% protein, and 12% lipid, was administered either at 3-hr or 12-hr postburn. Control groups received no food or a similar amount of saline by bolus infusion. All animals were allowed water ad libitum until 24-hr postburn when their MLN and intestinal segments were harvested for enumeration of viable CA. Blood was also collected for determination of serum IgG, C3, cortisol, and albumin. Compared to nonfeed animals, those with a single enteral feeding at 12-hr postburn had reduced numbers of CA translocating to the MLN (970 +/- 220 vs 7,120 +/- 2,130 CFU/g, p less than 0.02) and colonizing in the ileum (27,000 +/- 6,770 vs 104,000 +/- 23,550 CFU/g, p less than 0.01). Bolus feeding at 12 hr was associated with a lower cortisol level (237 +/- 55% of normal controls) than bolus feeding at 3 hr (310 +/- 58, p less than 0.02) or the nonfed group (326 +/- 66, p less than 0.01). Regardless of dietary treatment, serum cortisol levels correlated positively with the extent to which CA translocated to the MLN and negatively with C3 levels.

Enteral Feeding in Burn Hypermetabolism: Nutritional and Metabolic Effects of Different Levels of Calorie and Protein Intake

Enteral nutrition was provided by continuous pump-controlled gastrostomy tube feeding for 14 days in 97 guinea pigs bearing a 30% full thickness burn. Seven defined combinations of caloric and protein intake were studied. With a caloric intake of 175 kcal/kg/day, equaling the measured energy expenditure, the animals receiving 10% of calories as protein had a significantly greater postburn weight loss (p less than 0.05) and muscle mass depletion (p less than 0.05), and a significantly lower muscle nitrogen concentration (p less than 0.05), serum albumin level (p less than 0.01) and liver nitrogen content (p less than 0.01). With the same caloric intake but with more than 20% of calories as protein, the weight loss and the muscle wasting were reduced, but not abolished, and the serum albumin level and liver nitrogen content were normalized. Also with the diets containing 200 kcal/kg/day the muscle tissue depletion could not be abolished. However, with this caloric intake, the animals given 20% of calories as protein had a lower weight loss and a higher serum albumin level (p less than 0.01), but also a greater fat infiltration of the liver (p less than 0.01). At both levels of caloric intake, the nitrogen balance correlated significantly with the level of nitrogen intake but did not correlate with the changes of body weight. The incidence of diarrhea was lowest in animals fed 20% protein calories at a caloric intake of 175 kcal/kg/day. All things considered, the best metabolic and nutritional results were obtained with diets containing 20 to 30% of calories as protein and providing a caloric intake that paralleled the measured energy expenditure.

Candida albicans translocation across the gut mucosa following burn injury.

Normal guinea pigs were challenged intragastrically with Candida albicans 1 hr prior to a 30 or 50% flame burn to determine if burn injury increased translocation of the yeasts across gut mucosa. Tissues were harvested between 3 and 24 hr postburn and cultured on Sabouraud dextrose agar. Control animals (no yeast challenge) showed no yeast in intestinal homogenates or in the mesenteric lymph nodes (MLN). At a dose of 1 X 10(9) yeasts, they did not escape from the gut lumen, with either a 30 or 50% burn. At a dose of 2 to 4 X 10(10) organisms, they translocated to the MLN in 92% of the 50%-burned animals (P less than 0.001), 75% of the 30%-burned animals (P less than 0.05), and 12.5% of unburned animals. The ileal mucosa appeared to be the most susceptible site for yeast invasion. To observe the penetration through the gut mucosa and/or translocation to other tissues, yeasts were labeled with biotin before administration, and tissues were stained with avidin-peroxidase diaminobenzidine sequence. With biotinylated yeasts, phagocytized organisms were observed in large numbers in the lamina propria and mesenteric lymph nodes but they were not viable upon culture. Toluidine blue staining of semithin sections revealed that translocated yeasts were located selectively in the lymphoid follicles of the MLN, entrapped by macrophages.

Increased gut blood flow with early enteral feeding in burned guinea pigs.

The hemodynamic responses to early enteral feeding were assessed with fluid-resuscitated, 30% total body surface area-burned guinea pigs fed by means of tube gastrostomies. Regional blood flow and cardiac output were determined by a reference sample method, injecting 15 microns radiolabeled microspheres. During the initial 24 hours after burn injury, animals were given the same volume by continuous infusion of either lactated Ringers solution (LR group) or a liquid diet (20% protein, 12% lipid, and 68% carbohydrate; 175 kcal/kg/24 hr) (diet group). Although cardiac outputs in the LR and diet groups were not different from each other at 24 hours and no less than that in unburned control animals, the diet group showed higher blood flow to the jejunum (+55.7%) and cecum (+98.7%) than did the LR group. Burn injury caused little change of blood flow to tissues other than the intestine. In addition, early feeding after burn injury suppressed excessive cortisol response to burn shock. The increase in gut blood flow associated with enteral feeding could have an impact on mucosal barrier function.