Gastric emptying in humans: influence of different regimens of parenteral nutrition.

Intravenous administration of nutrients can suppress oral food intake. Inhibition of gastric emptying (GE) is a potential explanation for this process. Inhibition of GE during parenteral nutrition (PN) and attenuation of this by parenteral nutrition enriched with branched-chain amino acids (BCAAs) was examined in nine healthy males maintained on standard liquid diets for 6 d before each of three GE studies. GE was measured by scintigraphy after ingestion of a liquid test meal, at weekly intervals, after a 6-h infusion of Ringer lactate solution (RL), peripheral PN, or PN with half the amino acids replaced with BCAAs (BCPN). With PN, gastric emptying during the first 50 min was delayed by 38% compared with RL infusion; BCPN attenuated the effect, suggesting that postabsorptive control of food intake may act through changes in GE. These findings have clinical potential to reduce interference with appetite and to optimize food intake during PN administration.

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)

[Parenterally administered medium-chain triglyceride-induced changes in carnitine metabolism]. / Parenteral verabreichte mittelkettige Triglyzeride induzieren Veränderungen im Carnitin-Stoffwechsel.

Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate was studied in four healthy male adults. Glucose and amino acids were infused alone for three hours, then continued for another 5.5 hours together with a lipid emulsion containing only long-chain triglycerides or a mixture of medium-chain and long-chain triglycerides (50:50; w/w). During the fat-free infusion, the concentration of free carnitine rose, while the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 hours reduced free carnitine to lower values (32.4 +/- 4.7 mumols/L) than long-chain triglycerides infusion (44.4 +/- 2.7 mumols/L). By contrast, the plasma concentrations of short-chain acylcarnitines (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/L; p less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/L; p less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. These findings suggest that oxidation of medium-chain fatty acids is to some extent carnitine-dependent, whether or not transport into mitochondria is carnitine-mediated.

Nutritional and metabolic support.

The problem of hunger accompanies any mass casualty situation that results in large numbers of patients with traumatic and burn injuries complicated by sepsis and end organ failure. This is caused by the inability of many of these patients to eat. Such patients require artificial nutrition. A rescue operation that does not provide adequate artificial nutrition, no matter how well organized with respect to field stabilization, surgical intervention, and intensive care, will find many of its patients dying of multiorgan disorders due to nutritional failure. This article is concerned with how to provide such artificial nutrition.

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.

Medium-chain triglycerides induce alterations in carnitine metabolism.

Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate were studied in four healthy male adults. Glucose and amino acids were infused alone for 3 h, then continued for another 5.5 h together with a lipid emulsion containing only long-chain triglycerides or a 50:50% (wt/wt) mixture of medium-chain and long-chain triglycerides. During the fat-free infusion, the concentration of free carnitine rose, whereas the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 h reduced free carnitine to lower values (32.4 +/- 4.7 mumols/l) than long-chain triglycerides infusion (44.4 +/- 2.7 mumol/l). By contrast, the plasma concentrations of short-chain acylcarnitine (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/l; P less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/l; P less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. This suggests that intravenous medium-chain triglycerides are not metabolized independently of carnitine. Carnitine may play an important role in removing acyl and acetyl groups from mitochondria and in restoring the intramitochondrial CoA level. Fat substrates are converted into compounds that might be utilized by tissues that do not normally oxidize fatty acids, creating an interorgan energy cycle.

Growth hormone and pulmonary disease. Metabolic effects in patients receiving parenteral nutrition.

Six severely malnourished patients with chronic obstructive pulmonary disease were maintained for 3 days with infusions of 5% dextrose in water followed by 12 days of eucaloric total parenteral nutrition. On days 8 through 11, they received 30 micrograms/d of growth hormone and twice this amount on days 11 through 15. Growth hormone had no significant effects on the plasma concentration of glucose, cortisol, or glucagon but caused a 50% increase in insulin and a 250% increase in somatomedin C concentrations. A positive nitrogen balance of 2 g/d due to growth hormone was probably mediated by insulin. Growth hormone-induced increases in energy expenditure and fat oxidation and decrease in glucose oxidation cannot be accounted for by insulin. The ability of growth hormone to improve nitrogen balance may be particularly important for malnourished patients with chronic obstructive pulmonary disease who, because of their pulmonary insufficiency, are intolerant of excess nutrients.

Effects of glucose on nitrogen balance during high nitrogen intake in malnourished patients.

1. The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in 12 malnourished adult patients receiving parenteral nutrition with constant, very high nitrogen intake (500 mg of N/kg), high (105 kJ/kg) or low (30 kJ/kg) glucose intake and constant fat intake (7 kJ/kg). Each patient received each diet for 8-day periods in random order. 2. Energy balance and nitrogen balance were determined daily. Blood samples, taken at admission, during 5% (w/v) dextrose (D-glucose) infusion and at the end of days 7 and 8 of each diet, were analysed for urea, glucose, lactate, triacylglycerols, fatty acids, glycerol, 3-hydroxybutyrate, insulin and glucagon. 3. The effect of increasing glucose intake was to increase nitrogen balance by 0.60 +/- 0.25 (SEM) mg/kJ. At zero energy balance, nitrogen balance was 48 mg day-1 kg-1. This confirms findings of previous studies: that the effects of glucose on nitrogen balance are greater at high than at low nitrogen intakes, and that, in malnourished patients, unlike in normal adults, markedly positive nitrogen balance can be achieved at zero or negative energy balances. 4. Changes in nitrogen balance were due almost entirely to changes in urea excretion. 5. The high nitrogen intake markedly increased plasma insulin and glucagon concentrations and reduced glycerol, fatty acid and 3-hydroxybutyrate concentrations, independent of any glucose effect. Glucagon concentrations were significantly decreased by added glucose intake, an effect not previously seen at low nitrogen intakes. At this high nitrogen intake, the effects of added glucose appear to be mediated by both insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of glucose on fuel utilization and glycerol turnover in normal and injured man.

Rates of fat mobilization (glycerol turnover), and fuel utilization and energy expenditure (indirect calorimetry) were measured in normal subjects and injured or septic patients maintained on high or low iv intakes of glucose as their sole nutrient source during 3-day periods. Regimens were given consecutively to each subject in random order. Concentrations of glucose, glycerol, fatty acids, 3-hydroxybutyrate, urea, insulin, and glucagon were determined in plasma, and of epinephrine and norepinephrine in urine. In normal subjects, there was no increase in energy expenditure with increasing glucose, although estimated costs of glucose storage as glycogen or fat could account for an increase of 4%. Thus, storage costs of glucose do not necessarily constitute an obligatory increase in energy expenditure. Rates of glycerol turnover and fat oxidation, and plasma glycerol concentrations were lower with the high than the low rate of glucose infusion, and lower than values reported by others during fasting or glucose infusion. Rates of fat oxidation were higher and glucose oxidation lower in patients than in controls, even though insulin concentrations were more than twice as high in patients. This confirms previous studies comparing injured and septic patients to depleted patients or historical controls. Triglyceride cycle activity was higher in the injured and septic patients than in normal subjects, and could account for from 6% to 15% of the increase in energy expenditure, in agreement with reports for burn patients.

Functional and metabolic changes during feeding in gastrointestinal cancer.

The impact of feeding a hypercaloric parenteral solution on N balance, energy metabolism, and muscle strength has been investigated in cachectic patients with gastrointestinal cancer and in malnourished patients without evidence of cancer (controls). Patients were examined during 5% dextrose administration (D5W) for 2 days, followed by an infusion of a carbohydrate-based (53% carbohydrate, CB) or fat-based (55% fat, FB) diet with a constant protein intake. Diets were administered for 1 week each, in a randomized crossover design. During D5W, cancerous patients demonstrated a similar energy expenditure, but significantly lower N balance (p less than 0.005) than controls. Compared to control patients, N balance in cancerous patients was similar on the CB diet and significantly lower during the FB diet (p less than 0.025). Unlike the control patients, muscle strength and endurance tests did not improve after 2 weeks of feeding in cancerous patients. The cancerous patients differ from controls because they are hypercatabolic (especially during D5W administration), and they showed no improvement in muscle strength with 2 weeks of feeding.

Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake.

Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen.

A mathematical analysis of indirect calorimetry measurements in acutely ill patients.

Beside indirect calorimetry is generally accepted as reliable for evaluating energy expenditure (EE) and oxidation of carbohydrate (dCH) and fat (dF) in critically ill patients. Daily measurement of nitrogen excretion is usually included in the calculation of EE, dCH, and dF but it is difficult to perform in the clinical setting and is not necessary for accurate determination of EE. In this paper new equations, which are suitable for use with critically ill patients, are given for calculating EE, dCH, and dF without N-excretion measurements. With these equations the maximum errors for EE, dCH, and dF were 56, 179, and 306 kcal/d, respectively. The mean errors in 38 measurements of 26 critically ill patients were 27, 86, and 143 kcal/d, respectively. Measurement of EE by these equations is very accurate and suitable for both research and clinical use. Although the calculation of dCH and dF is much less precise, it can still given an indication of fuel utilization.

Fatty acid kinetics in man during chronic and acute illness.

Eight nutritionally depleted and five injured patients were studied prior to and during total parenteral nutrition (TPN). Five additional injured patients were studied at intervals while receiving only 5% dextrose. Fatty acid kinetics and oxidation were determined using an infusion of [1-14C]palmitate. Net substrate oxidation was calculated by indirect calorimetry. During TPN, resting energy expenditure rose from 109 to 119% and from 89 to 103% of predicted in injured and depleted patients, respectively. Free fatty acid (FFA) flux was unaffected, FFA oxidation and net fat oxidation (NFO) decreased by 60%. However NFO began higher in injured subjects (20.7 +/- 2.8 vs 14.6 +/- 0.9 kcal/kg/day, P less than 0.05) and remained higher during TPN (8.3 +/- 1.2 vs 5.6 +/- 0.9 kcal/kg/day, P less than 0.05). The proportion of NFO derived from immediate oxidation of circulating FFA was approximately 35%. The results indicate that, with glucose-based TPN, there is a discrepancy between suppression of FFA production and oxidation. We further conclude that sources of fatty acid which are not in rapid equilibrium with circulating plasma FFA contribute substantially to whole body fat oxidation.

Measurement of fatty acid oxidation: validation of isotopic equilibrium extrapolation.

Measurement of whole body substrate oxidation requires prolonged isotope infusion to attain plateau specific activity (SA) of expired CO2. We have investigated in 13 hospitalized patients a technique whereby plateau 14CO2 SA is extrapolated using computer curve fitting based upon the early exponential rise. A primed-constant infusion of albumin-bound 1-14C-palmitate was continued for 260 minutes with isotope priming of the secondary bicarbonate pool at 70 minutes. Plasma free fatty acid (FFA) SA reached steady state by 40 minutes and was 91% +/- 4% (SE) of values obtained at 190 to 260 minutes. At 70 minutes 14CO2 SA reached only 44% +/- 1% of the 190 to 260 minute values, which were consistently at plateau. The predicted steady state 14CO2 SA from the 40 to 70 minute curves and the FFA oxidation rates calculated from those values were 94% +/- 2% and 102% +/- 4%, respectively, of values measured at steady state (190 to 260 minutes). The relationship between predicted and measured values approximated the line of identity for 14CO2 SA (y = 0.90x + 0.14, r = .98, P less than .001) and FFA oxidation (y = 1.02x, r = .98, P less than .001). The results suggest that FFA oxidation can be accurately calculated using a short infusion of labeled FFA without bicarbonate pool priming, thus avoiding overpriming or underpriming and possibly allowing multiple studies and diminished radioisotope exposure.

The effects of injury and sepsis on fuel utilization.

The metabolic response to injury may be presumed to be adaptive, at least in terms of days to weeks. In the wild state where these patterns developed, the wounded organism has poor access to food and must live off its own stores of nutrients, mainly fat, and tissue proteins, mainly from muscle. In fasting, without injury, the organism conserves protein. In this condition there are reductions in blood glucose and insulin levels and increases in glucagon and fatty acid levels. Insulin-dependent tissues stop using glucose; the liver converts fatty acids to ketone bodies, which increase about 100-fold in the fasting human; and the brain substitutes ketone bodies for more than one half of what would otherwise be an obligatory consumption of 100 to 150 g glucose per day in humans. This substitution spares the amount of muscle protein required for gluconeogenesis in liver and kidney, and net N losses can be reduced to less than 6 g per day. Energy expenditure decreases up to 30%. The fasted, injured subject has additional nutritional requirements. Regeneration of the wound and rapidly proliferating white and red blood cells require a source of amino acids and other nutrients. Synthesis of acute-phase proteins required for host defense also needs amino acids. In addition, the wound, regenerating tissue, and white blood cells require large amounts of glucose for glycolysis. That the wound is poorly vascularized may be the major reason for hyperglycemia, which provides a glucose gradient between plasma and tissue high enough for extraction of sufficient glucose. The wound does not increase net consumption of glucose; rather, lactate returns to the liver to be converted again to glucose. Hyperglycemia due to the wound increases the requirements for gluconeogenesis from muscle protein, however. The high concentrations of counterregulatory hormones, cortisol, epinephrine, and glucagon will minimize glucose utilization by insulin-sensitive tissues, despite high concentrations of both glucose and insulin, but these hormones are not able to prevent suppression of ketone body synthesis in the liver. As a result, the brain continues to derive almost all its energy from oxidation of glucose. Synthesis of this glucose in liver is the biggest consumer of amino acids made available by net degradation of muscle protein. The metabolic response to injury, initiated by afferent nerve impulses and cytokines and mediated by increases in counterregulatory hormones and sympathetic activity, is a well-coordinated, well-regulated process controlled largely by the hypothalamus. Increased consumption of nutrients occurs simultaneously with but is not caused by increase in production.(ABSTRACT TRUNCATED AT 400 WORDS)