David H. Elwyn

Effects of hypercaloric glucose infusion on lipid metabolism in injury and sepsis.

UNLABELLEDnLipolysis was studied by measuring glycerol turnover (GTO) in injured and infected patients. GTO was elevated two to three times the normal values in five injured and four infected patients during D5W infusion. No correlation was found between GTO and plasma glycerol concentration in the two patient groups. GTO showed similar levels when measured during TPN in five injured and three infected patients. During TPN, plasma FFA levels remained unchanged in injured but decreased by 48% in septic patients. B-OH butyrate concentrations were high during D5W and dropped in both groups during TPN. Norepinephrine urinary output was high in both groups during D5W and TPN.nnnCONCLUSIONSn1) GTO was elevated two to three times the normal range in injury and infection; plasma glycerol concentration was not related to GTO. 2) In face of high catecholamine output, the insulin response to TPN did not inhibit TG breakdown but did decrease plasma ketone body concentrations.

Changes in respiratory control induced by amino acid infusions.

We compared the metabolic and respiratory responses to a 4-h infusion of an amino acid solution consisting primarily of branched-chain amino acids (BCAA) to those after a standard amino acid solution in healthy subjects. Both the BCAA solution and the standard amino acid solution increased minute ventilation (mean increase 22%, p less than .001, and 18%, p less than .01, respectively), mean inspiratory flow (19%, p less than .01, and 19%, p less than .05) and oxygen consumption (9%, p less than .02, and 5%, NS). PaCO2 decreased (mean decrease 6%, p less than .01); there was a major increase in the ventilatory response to CO2 inhalation during administration of the BCAA solution but not the standard amino acid solution. Increased plasma norepinephrine concentration (mean increase 75%, p less than .001) during the infusion of the standard amino acid solution but not the BCAA solution suggested increased sympathetic activity. The results demonstrate augmented respiratory effects of amino acid infusions by BCAA enrichment, and a dissociation between the respiratory stimulation, metabolic rate, and sympathetic activity.

Protein and energy sparing of glucose added in hypocaloric amounts to peripheral infusions of amino acids

After abdominal surgery, patients were given peripheral infusions of amino acids alone for 4 days followed by amino acids plus glucose for 4 days, or the same solutions in the reverse order. Although there was a wide variation in the response of individual subjects, the typical effect of glucose under these conditions was to reduce both nitrogen excretion (average of 2.8 g N/day) and resting metabolic expenditure (average of 110 kcal/day).

Components of nitrogen excretion in hospitalised adult patients on intravenous diets

Abstract The components of N excretion of 260 adult patients and 37 normal subjects receiving all nutrition intravenously were analysed retrospectively. The 237 patients studied at Columbia University, were classified as nutritionally depleted (67), post-operative (96), injured (43), and septic (31). Twenty-three septic patients were studied at the University of Toronto. Patient groups were stratified according to diet intake. Urinary urea N varied markedly with both diet and disease status. There was marked individual variability, coefficients of variation of about 40%, precluding estimates from diet and disease status alone. Non-urea excretion, in urine, stool and drainages, was markedly affected by disease status but unaffected by diet. Individual variability was proportionally as high as for urea. Nevertheless, since non-urea N is much smaller, estimates of non-urea N together with measurement of urea excretion may be useful for both research and clinical purposes. Estimates given are based on values for urinary non-urea N, stool, and, when present, diarrhoea and drainage, and also provide an estimate of probable error. Since the estimates are based on data from subjects receiving intravenous nutrition and vary with disease status, they are more accurate for similar patients on similar diets than estimates, currently in use, based on urine and stool measurements of normal subjects on oral diets.

Plasma Lipoprotein Pattern During Long-Term Home Parenteral Nutrition With Two Lipid Emulsions

Hypertriglyceridemia induced by short-term lipid infusions causes redistribution of neutral lipid components between endogenous lipoproteins and emulsion particles. To determine whether such redistribution occurs over a long-term infusion period and affects lipoprotein pattern, we studied seven patients with inflammatory bowel disease who received cyclic home parenteral nutrition for two consecutive periods of 3 months with two different lipid emulsions. During each period, they received in random order either an emulsion composed exclusively of soy-derived long-chain triglycerides (LCTs) or another emulsion containing an equal weight:weight mixture of long- and medium-chain triglycerides (MCTs/LCTs). Both emulsions contained 20 triglycerides (TGs) and 1.2 phospholipids. Lipids provided 50 of nonprotein energy. Blood samples were taken once a week, 1 hour before the end of infusion (during) and again after a 6- to 8-h lipid-free interval (baseline). During infusion, there was a moderate increase of plasma TGs and phospholipids and a slight decrease of plasma esterified cholesterol (CE) and free cholesterol. Most of the plasma TGs increase occurred in the very-low-density lipoprotein fraction (containing both emulsion particles and the endogenous very-low-density lipoprotein), but there was also an increase of TGs content in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) that was more pronounced with MCTs/LCTs. Acquisition by exogenous particles of CE transferred from LDL and HDL was significant for the LCT emulsion only. Although no change was observed in plasma lipid concentration of baseline samples during 3 months of home parenteral nutrition, some modifications were observed in the composition of lipoprotein fractions demonstrating a redistribution of lipid components.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein synthesis rates in rat muscle and skin based on lysyl-tRNA radioactivity

Measurement of protein synthesis in individual organs is important in understanding metabolic changes in injury, sepsis, or starvation. Methods, mostly isotopic, for measuring synthesis are plagued by problems of experimental design and interpretation. Thus it is desirable to use a variety of methods based on different assumptions. The present study is the first to isolate radioactive aminoacyl-tRNA in the study of protein synthesis in muscle and skin. Male rats, 200-300 g, trained to eat chow for 4 hr/day were studied at 2 hr (absorptive) or 16 hr (postabsorptive) after a meal. Under ether anesthesia, a tracer dose of L-[4-5-3H(N)]-lysine was infused at a constant rate. At 20, 30, or 40 min 1 ml of arterial blood was withdrawn and 2-g samples of skin and thigh muscle were quickly excised and frozen. Samples were pooled from 4 to 7 rats for each infusion period. Concentrations and specific activities were determined for plasma lysine, and for free, tRNA, and protein-bound lysine in muscle and skin. Protein renewal rates in absorptive and postabsorptive periods averaged 6 and 9% per day in muscle, and 20 and 35% in skin. The data for muscle confirms results of other methods and suggests little contribution of rapidly turning over protein. The contribution of skin to whole body protein synthesis, about 500 mg . 100 g-1 . day-1, is similar in magnitude to the contributions of muscle, liver, or intestine.

Increased body temperature secondary to total parenteral nutrition.

Administration of total parenteral nutrition (TPN) (glucose/amino acids), on the 2nd day after surgery, to a 26-year-old male with multiple fractures resulted in a rise in rectal temperature from 37.6 to 39°C. Resting energy expenditure showed a sustained 23% increase when the nutritional intake was changed from 5% dextrose to TPN. This case demonstrates that the increased metabolic rate associated with administration of TPN in acutely injured patients may be associated with an increase in body temperature.

Changes in metabolism and muscle composition associated with total hip replacement.

Metabolic changes in 10 patients undergoing total hip replacement were studied. Metabolic expenditure postoperatively remained within 5--10% of preoperative values. Net nitrogen loss for the postoperative period was less than 35 gm for the first 4 postoperative days, well below changes seen in major nonsurgical trauma. Fluid balance was positive in all patients for the first 4 postoperative days. Patients not in negative fluid balance by the fourth postoperative day should be closely monitored for complications. Recognition of delayed fluid excretion is essential in order to avoid the complications of further fluid loading in the postoperative period. Muscle composition reveals predictable changes in extracellular water, sodium, and chloride composition following surgery. Our data showed that metabolic changes following total hip replacement are in the order of major general surgical procedures and well below that observed with major trauma.

Resting energy expenditure in injured, septic, and malnourished adult patients on intravenous diets

Energy expenditures of 237 adult patients and 37 normal subjects receiving all nutrition intravenously were analysed retrospectively. Patients were classified as nutritionally depleted (67), post-operative (96), injured (43), or septic/depleted (31). Groups were further divided into those receiving either: (1) only 5% dextrose (D5W); (2) hypocaloric regimens including glucose and amino-acids; and (3) eucaloric or hypercaloric total parenteral nutrition (TPN) which also included fat. Resting energy expenditures (REE) of normal subjects on D5W were only 85% of predicted basal values based on either the Aub-Du Bois or Harris-Benedict equations. During D5W infusions, increases for the patient groups, above these values for normal subjects, varied depending on whether they were based on absolute values or ratios to predicted values. They were: (1) 1-11% for depleted; 1-21% for post-operative; 28-30% for injured; and 18-30% for septic/depleted patients. The average increase in REE with TPN was 10%. Variability within the patient groups was high, reducing the utility of these values as a basis for estimating energy requirements of patients needing artificial nutrition. Coefficients of variation averaged 15% across patient groups when the data were expressed in kJ/kg, and were reduced only slightly, to 12%, when data were expressed as ratios to predicted values. Thus, 1 3 of the patients would differ by more than 12% from mean values, and 1 out of 20 by more than 24%. Properly performed measurements of individual energy expenditure are therefore superior to values predicted from equations or average values previously obtained from patient groups and should be used wherever possible, particularly in the very sick.

Nutritional and metabolic effects of enteral and parenteral feeding in severely injured patients

Abstract Patients after accidental injury or major abdominal surgery were given 5% dextrose for 1–2 days followed by either enteral or parenteral nutrition. Nutrient intake was about equal to estimated total energy expenditure. N intake averaged 210 mg/kg. Administration of nutrients reached full strength within 2 days. Energy and N balances were zero or positive at day 3 and thereafter. By day 6 there were significant increases in plasma insulin and amino acids and decreases in glycerol and fatty acid concentrations, compared to values during 5% dextrose administration. Increases in plasma glucose were not significant. Minor differences in plasma amino acid patterns between groups were due to differences in composition of amino acids administered. There were no significant nutrition or metabolic differences between the two groups, despite substantial amounts of diarrhoea in the enteral group. Since enteral nutrition maintains intestinal mucosa better than parenteral, is cheaper, and obviates the risks of a central catheter, it appears to be the method of choice whenever practicable, even in patients after severe injury or major surgery. These findings are consistent with previous observations in surgical or cancer patients and normal subjects.