Effect of age on substrate oxidation during total parenteral nutrition

OBJECTIVE: Parenteral nutrition is increasingly used in the elderly. Aging is accompanied by metabolic changes that can modify substrate use. We compared substrate oxidation during cyclic total parenteral nutrition (TPN) in elderly and middle-aged patients. METHODS: Twelve elderly patients (eight women, four men; 72 +/- 5 y) and 12 middle-aged patients (nine women, three men; 39 +/- 13 y) who were on cyclic TPN for intestinal failure were investigated while in stable condition after at least 15 d of TPN. No patient was diabetic. Indirect calorimetry was performed during fasting and every 30 min during the 3 h of TPN infusion and 3 h after infusion, allowing the measurement of nutrient oxidation. Blood samples were obtained every hour for the measurement of glucose, insulin, triacylglycerols, and free fatty acids. RESULTS: In the fasting state, resting energy expenditure was significantly higher in the elderly patients than in the middle-aged patients (39.3 +/- 8.1 versus 31.9 +/- 4.3 kcal/kg of fat-free mass per day, P = 0.008). During TPN, lipid oxidation was significantly higher in the elderly patients than in the middle-aged patients (1.09 +/- 0.17 versus 0.84 +/- 0.27 mg x kg(-1) x min(-1), P = 0.011); glucose oxidation was significantly lower in the elderly patients than in the middle-aged patients (2.19 +/- 0.93 versus 3.22 +/- 1.54 mg x kg(-1) x min(-1), P = 0.038). Areas under the curves of glycemia and free fatty acids were significantly higher in the elderly patients. CONCLUSION: In the elderly, TPN was associated with significantly higher lipid oxidation and lower glucose oxidation than in younger patients. TPN formulas and flow rates should therefore be adapted in the elderly.     

Substrate efficacy in early nutrition support of critically ill multiple trauma victims.

The metabolic consequences of excessive nutrition support in patients have been increasingly recognized in recent years. Time-dependent optimal nutrition support is desired for an early and uncomplicated recovery after severe injury or illness. Metabolic effects of adding balanced amino acids to glucose infusion during total parenteral nutrition were investigated in 18 patients after major trauma (injury severity score 32 +/- 2). Two studies were conducted on each subject, one in the early "flow" phase of injury (40-60 hours postinjury) in the basal state without any dietary intake and then after 4 to 6 days of intravenous nutrition provided solely as glucose (24 +/- 2 kcal/kg per day, 80% resting energy expenditure, n = 8) or isocaloric glucose (28 +/- 3 kcal/kg per day) with amino acids (275 +/- 28 mg of nitrogen per kilogram per day, n = 10). Whole-body fuel substrate kinetics were studied for energy metabolism (indirect calorimetry), protein kinetics (primed-constant infusion of 15N glycine), and lipid mobilization (two-stage infusion of 10% glycerol). Injury-induced hypoaminoacidemia was equally modulated whether the glucose-based nutrition had amino acids or not. The negative nitrogen balance is reduced similarly in both groups. Protein breakdown rate is significantly (p = .025) decreased in both groups and it is more so (30% vs 18%) in patients receiving total parenteral nutrition. Intravenous nutrition could not stimulate protein synthesis. Whole-body lipolysis rate as well as net fat oxidation rate are suppressed more when glucose alone is given, and this also results in less reesterification. Provision of intravenous glucose alone, not to exceed the resting energy expenditure, seems to be superior to isocaloric glucose with amino acids during this early catabolic flow phase of injury because the injured body could not assimilate this exogenous amino acid.     

Comparison of substrate utilization by indirect calorimetry during cyclic and continuous total parenteral nutrition

Five male adult home patients were studied in a randomized order under continuous (24 h/d) and nocturnal cyclic (15 h/d) isocaloric, isonitrogenous total parenteral nutrition (TPN). They received 2626 +/- 265 total kcal/d as 60% dextrose and 40% lipids; the 3-h lipid infusion was followed by the dextrose amino acid infusion on both regimens. Substrate oxidation was measured by indirect calorimetry during four periods on the fourth day of each regimen. During cyclic TPN net lipogenesis occurred with a nonproteic respiratory quotient (npRQ) greater than 1 during dextrose amino acid infusion followed by net lipolysis with an npRQ less than 1 during the nonnourishing phase. In contrast, during continuous TPN net lipogenesis persisted with an npRQ greater than 1 over the 21 h of dextrose amino acid infusion. During the 3-h lipid infusion, fat oxidation was observed during both regimens but was more pronounced during cyclic TPN (p less than 0.05). As a consequence, 24-h lipid oxidation was higher and 24-h dextrose utilization lower during cyclic vs continuous TPN (p less than 0.05). These results suggest that cyclic TPN when alternating between substrate storage and oxidation, mimics the physiological pattern of oral feeding.     

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.     

Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model

A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate.     

Metabolic response of simultaneous versus sequential intravenous administration of amino acids and energy substrates to rats

Three groups of rats were maintained on total intravenous nutrition for ten days. Group SA and SB were infused sequentially (2 X 12 h periods per day), SA received amino acids (AA) during the night and carbohydrates (CHO) + FAT during the day. The SB group received nutrients in the opposite order. A control group received a mixed solution simultaneously for 24 h/day. The sequentially fed groups showed a lower weight gain (2.4 +/- 0.4, 2.6 +/- 0.2 vs 4.9 +/- 0.3 g/day), nitrogen balance (95 +/- 7, 95 +/- 6 vs 139 +/- 7 mg/day) and nitrogen utilization (69 +/- 3, 67 +/- 3 vs 87 +/- 3%) compared with the control group. Administration of energy substrate in the SA and SB was a stronger denominator for O2 consumption and changes in RQ than the periods of physical activity. Control animals did not show any diurnal variations in O2 and RQ. Glucose, FFA and insulin were higher with CHO + FAT administration compared to AA infusion or simultaneous AA/CHO/FAT administration. In conclusion, the results suggest that simultaneous administration of a mixture of AA/CHO/FAT is preferable for whole body nitrogen economy during TPN.     

Amino acids enhance insulin resistance to exogenous glucose infusion in overnight-fasted humans

The role that amino acids play in regulating exogenous glucose infusion during hyperinsulinemia was examined in overnight-fasted volunteers. Each study consisted of both a 30-minute basal period and a 4-hour experimental period during which insulin was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU/kg/min with euglycemia maintained. Two protocols were used. In the first (I), subjects were allowed to develop hypoaminoacidemia, and in the second (II), plasma amino acid levels were maintained near basal by frequently monitoring plasma leucine levels in conjunction with exogenous infusion of an L-amino acid solution. The amount of amino acids infused were 0.85 +/- 0.11, 1.53 +/- 0.17, 1.97 +/- 0.13, 2.18 +/- 0.50, 2.78 +/- 0.61, and 2.83 +/- 0.44 mg/kg/min at escalating insulin doses, respectively. When amino acids were infused, the amount of glucose required to maintain euglycemia was lower at each insulin dose used (4.5 +/- 0.3 vs 3.6 +/- 0.4, 7.6 +/- 0.5 vs 6.9 +/- 0.3, 10.4 +/- 1.0 vs 8.7 +/- 0.5, 13.3 +/- 0.8 vs 10.2 +/- 0.4, 14.7 +/- 0.8 vs 11.7 +/- 0.6, and 14.9 +/- 0.6 vs 11.8 +/- 0.8 mg/kg/min at escalating insulin doses, respectively; p less than 0.05). The calculated maximal infusion rates were 15.8 +/- 0.6 vs 12.6 +/- 0.4 mg/kg/min (protocol I vs II, p less than 0.001), while the concentrations required to achieve half-maximal rates were 153 +/- 22 and 134 +/- 22 microU/ml (p = ns), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of glucose vs. Glucose fat solutions in cancer patients: A controlled crossover study

The purpose of this investigation was to evaluate in a randomised crossover study the effects on nutritional status of two isonitrogenous-isocaloric regimens of total parenteral nutrition (TPN) in 12 severely cachectic cancer patients. The regimens consisted of (1) G: 50 kcal of glucose.kg(-1).day(-1) + 2g amino-acids.kg(-1).day(-1) (2) GL: 30 kcal glucose and 20 kcal lipids.kg(-1) + 2g amino-acids.kg(-1).day(-1). Regimens G and GL were delivered sequentially for a period of 10 days each. Six patients (Group A) were randomised to receive regimen G first and regimen GL subsequently. In Group B patients the regimens alternated in the opposite way. The following nutritional variables were measured before TPN, after regimen G and after regimen GL: weight, arm circumference, arm muscle circumference, triceps skin fold, serum proteins, serum albumin, cholinesterase, transferrin, pre-albumin, retinol-binding protein, peripheral lymphocytes, cumulative nitrogen balance and mean urinary excretion of creatinine and 3-methylhistidine. The data showed that body weight and retinol-binding protein significantly increased with both G and GL regimens. No difference was found in the remaining variables, not even when comparing regimen G to GL. Increase in retinol-binding protein and in nitrogen balance were significantly better in the first period of treatment than in the second. These results show that the two regimens had a similar impact on the nutritional status of the cachectic cancer patients and choice between a glucose or a glucose-fat TPN should depend mainly on tolerance of the patients, duration and cost of therapy.     

Omega-3 fatty acid supplementation increases anti-inflammatory cytokines and attenuates systemic disease sequelae in experimental pancreatitis

BACKGROUND: The cytokines involved in the systemic inflammatory response in acute pancreatitis (AP) comprise lipid mediators (eg, prostanoids, thromboxanes, leukotrienes) generated from arachidonic acid (AA) and eicosapentaenoic acid (EPA). The AA-derived mediators are generated from omega-6-fatty acid (FA) and have strong proinflammatory effects and the EPA-derived mediators generated from omega-3-fatty acid are less active or even exhibit anti-inflammatory effects. Basic parenteral nutrition delivers omega-6-FA and omega-3-FA at a ratio of approximately 7:1. AIM: To investigate whether altering the FA composition by fish oil supplementation (omega-3-FA) affects cytokine production and the parameters reflecting systemic disease severity in experimental AP. METHODS: Severe AP was induced in 30 rats by standardized intraductal infusion of bile salt and IV cerulein. Six hours after AP induction, rats were randomized to TPN using commercial solutions with identical amounts of glucose, amino acids, and fat but different FA compositions: group 1 received a soybean-based fat solution without additional fish oil and group 2 was supplemented with 0.2 g/kg per day fish oil. TPN was continued for 2 days. Serum concentrations of IL-6 and IL-10 were measured before and after AP induction and at 24 and 48 hours after starting TPN. Routine cardiorespiratory and renal parameters were monitored to assess the systemic response at the organ level. RESULTS: Animals treated with fish oil had significantly higher IL-10 values (at 24 hours, 63 +/- 7 versus 46 +/- 3 pg/mL), produced more urine (28 +/- 0.9 versus 21 +/- 1.6 mL), and had significantly fewer episodes of respiratory dysfunction (defined as a pO2 < 80 mm Hg or pCO2 > 50 mm Hg for >15 minutes; 29% versus 67%) during the observation period. CONCLUSIONS: Altering eicosanoid mediator precursor availability by infusion of (omega-3 fatty acid increases anti-inflammatory cytokines in this model of AP. This together with improved renal and respiratory function suggests that the systemic response to pancreatic injury is attenuated.     

Effects of a parenteral nutrition regimen containing dicarboxylic amino acids on plasma, erythrocyte, and urinary amino acid concentrations of young infants

Plasma, erythrocyte, and urinary amino acid concentrations were measured in young infants infused with a solution containing glutamate and aspartate. Eight infants (1.2 to 2.8 kg) were fed parenterally (80 kcal/kg/day) with two regimens containing dextrose (15 g/kg/day), amino acids (2 g/kg/day), and lipid (2 g/kg/day) for successive 3-day periods in a cross-over design. The regimens differed only in the amino acid source. One regimen (I) provided glutamate (1.5 mmol/kg/day) and aspartate (1.0 mmol/kg/day), while the other regimen (II) did not. The mean (+/- SD) plasma glutamate concentration was slightly, but significantly higher (89.9 +/- 28.5 microM) during infusion of regimen I than regimen II (66.5 +/- 19.8 microM), but values did not differ significantly from values observed in normal, orally fed premature infants (107 +/- 36 microM). No significant differences were noted in either plasma or erythrocyte aspartate concentrations, or in erythrocyte glutamate concentration. Since plasma and erythrocyte levels of dicarboxylic amino acids remained within the normal range, the data indicate no hazard to young infants from infusion of dicarboxylic amino acids at this level.     

Influence of stress, depletion, and/or malignant disease on the responsiveness of surgical patients to total parenteral nutrition

We performed a series of 14C[urea] infusions to assess the effect of depletion (greater than 15% decrease in body weight), stress (VO2 greater than 130 mumol.kg-1.min-1), and cancer on the basal rate of net protein catabolism (NPC) and the response of patients to total parenteral nutrition (TPN). Depleted patients had low rates of NPC (0.8 +/- 0.1 g.kg-1.d-1) compared with nondepleted patients (p less than 0.05) and during TPN anabolism was achieved (0.5 +/- 0.2 g.kg-1.d-1). Gastrointestinal (GI) cancer patients had rates of NPC similar to those of normal volunteers; during TPN, NPC approximated zero. Severely stressed (SS) nondepleted patients had high rates of NPC (2.7 +/- 0.2 g.k-1.d-1) whereas SS-depleted patients had lower (p less than 0.05) rates of NPC (1.9 +/- 0.3 g.kg-1.d-1); both groups of SS patients remained catabolic despite TPN (1.2 +/- 0.3 and 0.5 +/- 0.2 g.kg-1.d-1, respectively). In response to TPN, depleted patients become anabolic, GI cancer patients stop losing protein but do not become anabolic, and stressed patients remain catabolic and continue to loss protein.     

Thermogenesis from intravenous medium-chain triglycerides

Eighteen hospitalized patients dependent on total parenteral nutrition (TPN) were randomly enrolled into a prospective study comparing intravenous long-chain triglycerides (LCT) with a physical mixture of 75% medium-chain triglycerides (MCT) and 25% LCT. The TPN was given continuously as amino acids and glucose over 5 days with the respective lipid emulsion given intermittently during each day for 10 hr. Indirect calorimetry was measured on each patient before the lipid emulsion was administered in the morning and again 10 hr later near the end of the lipid infusion, on days 1, 3, and 5. Resting energy expenditure, VO2, VCO2, and calculated fat oxidation were shown to increase during MCT infusion but not during LCT administration, (resting energy expenditure 899 +/- 37 to 1085 +/- 40, compared with 978 +/- 23 to 976 +/- 39, kcal/m2 body surface area [BSA]/day, respectively, p less than 0.0002; VO2: 129.9 +/- 5.2 to 157.2 +/- 5.9, compared with 140.9 +/- 3.6 to 141.2 +/- 5.9 ml O2/min/m2 BSA, respectively, p less than 0.0005; and VCO2: 110.7 +/- 4.4 to 127.5 +/- 4.3, compared with 118.3 +/- 2.8 to 118.0 +/- 5.3, ml CO2/min/m2 BSA, respectively, p less than 0.0076; calculated fat oxidation 10.7 +/- 1.5 to 19.3 +/- 2.4, compared with 20.0 +/- 2.7 to 20.0 +/- 3.6, kcal/m2 BSA/hr, respectively, p less than 0.014). Respiratory quotient tended to fall with lipid infusion but did not change statistically. Body temperatures were unaltered by either fat infusion. It is concluded that TPN consisting of MCT causes an increased thermogenesis, most likely through increased fat oxidation, reflective of MCT's property as an obligate fuel. The increased thermogenesis occurs without an increase in body temperature.     

Early curbing of protein hyper-catabolism in postoperative patients by nutritional support with glucose plus amino acids, but not with glucose alone

This work attempts to determine if there are differences in protein metabolism in post-surgical patients who receive parenteral nutrition with amino acids plus glucose (G+AA) or conventional gluco-salinal solution (GS). Eighteen patients submitted to gastrointestinal surgery were randomized and double-blindly administered either G+AA (1 g AA/kg x d and 28 kJ/kg x d), or GS (28 kJ/kg x d). Protein metabolism was determined 12 h after surgery (day 0) and after 5 days of nutritional support. On day 0, protein breakdown was similarly elevated, with respect to reference values, in both groups (GS: 4.62 +/- 0.25; G+AA: 5.25 +/- 0.50 g prot/kg x d) as a result of surgical stress. These values increased significantly at day 5 (P < 0.03) with the administration of GS to 6.93 +/- 1.00 g prot/kg x d, while they decreased (P < 0.002, 3.30 +/- 0.42 g prot/kg x d) with G+AA. Protein synthesis was increased (5.69 +/- 0.86 g prot/kg x d) with GS (P < 0.02), and was decreased (2.79 +/- 0.44 g prot/kg x d) with G+AA (P < 0.0002). Both synthesis and breakdown were inside normal reference values after 5 days for group G+AA. In both groups, nitrogen balance did not change significantly at day 5 compared to day 0. G+AA is effective in curbing the hypermetabolism produced by postoperative stress, achieving normal protein metabolism in 5 days, while GS increases the protein breakdown and synthesis. Nitrogen balance does not detect these modifications of the protein metabolism. Undernutrition on prognosis is not yet fully recognized.     

The mode of delivery of parenteral multivitamins influences nutrient handling in an animal model of total parenteral nutrition

BACKGROUND: Very low birthweight preterm infants receive early total parenteral nutrition (TPN) to optimize protein balance. Adding multivitamins (MVP) to the lipid emulsion (MVP+LIP) rather than to the amino acid+dextrose moiety of TPN (AA+MVP) limits the effects of light exposure on lipid peroxidation and vitamin loss. AIM: Compare the effects of the mode of delivery of MVP on nutrient handling and indices of oxidant stress. METHODS: Three-day old guinea pig pups were assigned to TPN containing MVP+amino acids+dextrose+heparin and electrolytes, with lipids provided separately (AA+MVP). Solutions were light exposed (LE, n = 8) or light protected (LP, n = 9). In a further group (n = 7), MVP was co-administered with the lipid moiety and light exposed (LIP+MVP). Variables measured in urine (creatinine, nitrogen, vitamin C) and in liver (protein, glutathione, isoprostane, vitamins A, E, C) were compared by ANOVA. RESULTS: Urinary nitrogen and vitamin C were higher (P<0.05) during LE, while hepatic levels of vitamin C were higher (P<0.05) with LIP+MVP. These results were not related to total peroxide levels in TPN or to markers of oxidant stress. CONCLUSION. Co-administration of MVP with lipid or light protected amino acids offers comparable beneficial effects on nitrogen and vitamin C metabolism.     

Net hepatic gluconeogenic amino acid uptake in response to peripheral versus portal amino acid infusion in conscious dogs

These studies were conducted to determine the effect of route of gluconeogenic amino acid delivery on the hepatic uptake of the amino acids. After a sampling period with no experimental intervention (basal period), conscious dogs deprived of food for 42 h received somatostatin, intraportal infusions of insulin (3-fold basal) and glucagon (basal), and a peripheral infusion of glucose to increase the hepatic glucose load 1.5-fold basal for 240 min. A mixture of alanine, glutamate, glutamine, glycine, serine and threonine was infused intraportally at 7.6 micromol. kg(-1). min(-1) (PorAA group, n = 6) or peripherally at 8.1 micromol. kg(-1). min(-1) (PerAA, n = 6), to match the hepatic load of gluconeogenic amino acids in PorAA. During the infusion period, there were no differences in PerAA and PorAA, respectively, with regard to arterial plasma insulin (144 +/- 18 and 162 +/- 18 pmol/L), glucagon (51 +/- 8 and 47 +/- 11 ng/L), hepatic glucose load (199.8 +/- 22.2 and 210.9 +/- 16.6 micromol. kg(-1). min(-1)), net hepatic glucose uptake (2.8 +/- 2.2 and 2.2 +/- 1.7 micromol. kg(-1). min(-1)), hepatic load of amino acids (68 +/- 14 and 62 +/- 7 micromol. kg(-1). min(-1)), or net hepatic glycogen synthesis (11.1 +/- 2.2 and 8.9 +/- 2.2 micromol. kg(-1). min(-1)). The net hepatic uptake of glutamine (2.1 +/- 0.4 vs. 0.8 +/- 0.3 micromol. kg(-1). min(-1)) and the net hepatic fractional extractions of glutamine (0.11 +/- 0.02 vs. 0.05 +/- 0.02) and serine (0.41 +/- 0.03 vs. 0.34 +/- 0.02) were greater in PorAA than in PerAA (P < 0.05). We speculate that one or more of the amino acids in the mixture causes enhancement of the net hepatic uptake and fractional extraction of glutamine, and perhaps other gluconeogenic amino acids, during intraportal amino acid delivery.     

Metabolic and thermogenic response to continuous and cyclic total parenteral nutrition in traumatised and infected patients

16 traumatised or infected patients on mechanical ventilation were randomised to continuous TPN or to cyclic TPN after a 24-h period of glucose infusion (1.25 kJ x kg BW(-1) x h(-1)). Energy supply was equivalent to 1.3 x baseline energy expenditure. Glucose, fat and amino acids were administered at a constant rate over 24 h in the continuous TPN group and over 12 h, followed by glucose (1.25 kJ x kg BW(-1) x h(-1)), in the cyclic TPN group. Nutrient-induced thermogenesis was lower during continuous than during cyclic TPN (5 +/- 4 vs. 12 +/- 7%, mean +/- SD, p < 0.05), as was the increase in CO(2) elimination (13 +/- 11 vs. 30 +/- 7%, respectively, p < 0.01). Energy balance was more positive during continuous TPN. In both groups, energy expenditure reached a plateau during the first 12 h of TPN infusion. The lower nutrient-induced thermogenesis and more positive energy balance, indicates a more efficient utilisation of nutrients during continuous than during cyclic TPN. The lower CO(2) production during continuous TPN, may be advantageous when respiratory function is compromised. The plateau in energy expenditure in response to TPN infusion may be useful as a guideline for nutritional therapy.     

Enhanced rate of ethanol elimination from blood after intravenous administration of amino acids compared with equicaloric glucose

AIMS: To investigate the effect of an amino acid mixture given intravenously (i.v.) on the rate of ethanol elimination from blood compared with equicaloric glucose and Ringer's acetate as control treatments. METHODS: In a randomized cross-over study, six healthy men (mean age 23 years) fasted overnight before receiving either Ringer's acetate, glucose or the amino acid mixture (Vamin 18 g N/l) by constant rate i.v. infusion over 4.5 h. Ethanol (0.4 g/kg) was given by an i.v. infusion lasting 60 min during the time each of the treatments was administered. At various times post-infusion, blood samples were taken for determination of ethanol by headspace gas chromatography. Blood glucose and heart rate were monitored at regular intervals. Concentration-time profiles of ethanol were plotted for each subject and the rate of ethanol disappearance from blood as well as other pharmacokinetic parameters were compared by repeated measures analysis of variance. RESULTS: The rate of ethanol elimination from blood was increased significantly (P < 0.001) after treatment with amino acids (mean +/- SD, 0.174 +/- 0.011 g/l/h) compared with equicaloric glucose (0.121 +/- 0.016 g/l/h) or Ringer's acetate (0.110 +/- 0.013 g/l/h). Heart rate was also slightly higher during infusion of the amino acid mixture (P < 0.05). CONCLUSIONS: When the rate of ethanol elimination from blood is relatively slow, such as after an overnight fast, it can be increased by approximately 60% after treatment with i.v. amino acids. The efficacy of amino acid treatment was not related to the supply of calories because glucose was no more effective than Ringer's acetate. We suggest that amino acids might increase hepatic oxygen consumption, resulting in a more effective conversion of NADH to NAD+ in mitochondria. An important feature of the experimental design was ensuring hepatic availability of amino acids during much of the time that ethanol was being metabolized.     

Oligosaccharides as an intravenous energy source in postsurgical patients: utilization when infused with glucose, amino acids, and lipid emulsion

Utilization of intravenously administered oligosaccharides was evaluated in postsurgical patients by infusing oligosaccharides simultaneously with glucose, amino acids, and lipid emulsion for 4 d postoperatively. Seven patients were infused with a nutritional regimen providing glucose, amino acids, lipid emulsion, and oligosaccharides and seven patients received a similar regimen without oligosaccharides. Patients infused with oligosaccharides received an overall mean (+/- SD) of 144 +/- 41.0 g oligosaccharides per day. The mean overall excretion of total glucose (free plus oligosaccharide-bound) was significantly greater in patients infused with oligosaccharides (65.1 +/- 33.2 g/d) than in controls (1.83 +/- 1.55 g/d). Overall oligosaccharide utilization for the 4-d period was 48.7 +/- 10.1%. Plasma oligosaccharide concentrations increased from a baseline value of 2.43 +/- 1.90 mg/dL to 58.1 +/- 42.3 mg/dL after 4 d of oligosaccharide infusion, suggesting accumulation.     

Effects of long-chain triglyceride emulsions on reticuloendothelial system function in humans

Parenteral administration of long-chain triglyceride emulsions has been shown to have deleterious effects on reticuloendothelial system function in animal models. It is unknown whether this interference occurs in humans with clinically relevant doses of intravenous fat. Two studies were done. Eighteen patients were prospectively enrolled for study. Patients received full feeding by continuous total parenteral nutrition (amino acids 1.5 g/kg/day and dextrose 4.5 g/kg/day) with 33.1 kcal/kg/day. Forty-three % of the nonprotein calories were provided as soybean oil emulsion (Travamulsion 20%) and was administered intravenously over 10 hr (0.130 g/kg/hr). Reticuloendothelial system function was determined by measuring the change in the clearance rate of intravenously injected 99mTc-sulfur colloid (TSC) in each patient. In study 1 (n = 10), one day of lipid (10 hr) was infused, with the clearance of 99mTc-sulfur colloid measured before the lipid was infused and then during the last hour of the 10-hr infusion. In study 2 (n = 8), the clearance rates were measured before the lipid emulsion was begun, and then during the last hour of the infusion on the 3rd day. Clearance rates for TSC after 10 hr of lipid infusion in study 1 did not differ (0.27 +/- 1/min to 0.26 +/- 0.1/min, p greater than 0.10). However, after 3 days of lipid infusion (10 hr/day), a statistically significant reduction in TSC was seen (0.46 +/- 0.08/min-0.27 +/- 0.03/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)