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Recent studies have demonstrated that an altered pattern of substrate mobilization and fuel utilization exists in patients who are acutely ill secondary to either injury or infection. These studies have important implications regarding the nutritional support of these patients. This review addresses some of the metabolic sequelae of total parenteral nutrition with hypertonic glucose as the primary source of non-protein calories. The consequences of administering glucose calories in excess of energy requirements are considered. The patterns of gas exchange, fuel utilization and fuel storage in nutritionally depleted and hypermetabolic patients are discussed with specific reference to fat metabolism. Administration of glucose in hypercaloric quantities may produce a respiratory as well as a metabolic stress. The former appears to be related to a ventilatory stimulus associated with an increased rate of carbon dioxide production. In acutely ill patients, this response is magnified and there is also a considerable rise in oxygen consumption and free norepinephrine excretion. It is this group of patients which shows the most profound elevation in minute ventilation. The metabolic pathways and regulatory mechanisms which may be involved are discussed. A scientific approach to substrate administration in acutely ill patients can be taken only after these patterns of metabolic responses have been fully elucidated.

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 degrees 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.

Free fatty acid (FFA) metabolism was studied in 18 traumatized and/or septic patients. Each patient was studied while receiving 5% dextrose (D5W) and after 4 to 7 days of total parenteral nutrition (TPN). Nonprotein energy during TPN was given either entirely as glucose (Glucose System) or as equal portions of intravenous fat and glucose (Lipid System). Plasma FFA concentrations were in the normal range on D5W and decreased markedly with TPN. FFA turnover was higher than normal on D5W and did not decrease significantly with TPN. The poor correlation between these two variables emphasizes the need to perform kinetic studies to characterize FFA metabolism in trauma and sepsis. Plasma FFA oxidation and net whole body fat oxidation measured by indirect calorimetry were in the normal range on D5W, 35 and 82%, respectively, of resting energy expenditure (REE). With a glucose intake averaging 108% of REE, plasma FFA oxidation and net fat oxidation decreased to 17 and 13%, respectively, of REE. Nonprotein RQ increased only to 0.94 despite administration of glucose in excess of REE, indicating an abnormal persistence of fat oxidation. During D5W administration, plasma FFA accounted for less than one half of total fat oxidation, indicating that unlabeled fat, such as tissue or plasma triglycerides not in rapid equilibrium with plasma FFA, accounted for the bulk of fat oxidation. Glucagon concentrations which were high on D5W did not decrease significantly with TPN. Insulin concentrations were normal on D5W and increased in response to TPN. The abnormal hormonal milieu may account for much of the abnormal fat metabolism. Administration of large amounts of glucose decreased FFA oxidation much more than FFA mobilization. Thus, the infused glucose acts to increase the rate of "futile cycling" of FFA in these acutely ill patients.

The effects of increasing nitrogen intake were studied in 10 nutritionally depleted patients receiving total parenteral nutrition. After 1 to 2 days on 5% dextrose, the patients received, in random order, intravenous diets containing either a low (180 mg/kg . day) or high (364 mg/kg . day) nitrogen content. Equicaloric amounts of glucose and fat emulsion were given. Total energy intake averaged 33.0 kcal/kg . day corresponding to 1.31 X resting energy expenditure or 1.08 X total energy expenditure. Nitrogen and energy balances were measured daily. Concentrations of glucose, glycerol, fatty acids, triglycerides, urea, insulin and glucagon in plasma, and of beta-hydroxybutyrate in whole blood were measured during the last 2 days of each diet period. An increase in plasma urea was the only change in hormone or substrate concentrations identified. Resting energy expenditure increased approximately 10%, going from 5% dextrose to the low and from the low to the high N diet. Nitrogen balances were 0.21 and 0.61 mg N/kg . day on the low and high N diets. Nitrogen retention of 21% of the increment in intake, three times that seen in normal adult subjects, indicates that the malnourished patients in this study responded in a manner similar to growing organisms. Attainment of markedly positive N balance at, or close to, zero energy balance indicates that lean body mass can be restored without excessive energy intakes which may often be undesirable.

This study examines the influence of total parenteral nutrition (TPN) compared with 5% dextrose (D5) infusion on skeletal muscle and adipose tissue lipoprotein lipase (LPL) activity in nutritionally depleted, injured and infected patients. The plasma concentrations of glucose, free fatty acid (FFA), triglyceride and insulin were also measured. During TPN, nutritionally depleted subjects showed an increase in adipose tissue LPL activity, "fat cell size," and plasma insulin concentration. Skeletal muscle LPL activity and plasma FFA concentration decreased. In comparison, trauma patients showed a less marked rise in adipose tissue LPL activity and skeletal muscle LPL activity increased. Infected patients had a much smaller rise in adipose tissue LPL activity than either of the other groups, and muscle activity rose. The depleted and injured patients showed a linear relationship between adipose tissue LPL activity and plasma insulin concentration and an inverse hyperbolic relationship between adipose tissue LPL activity and plasma FFA concentration.

Changes in serum albumin levels and body weight are often used as indicators of the efficiency of a nutritional support regimen. Patients with moderate nutritional depletion demonstrate two distinct patterns of response during refeeding. The first is characterized by a decrease in the previously expanded extracellular fluid space with a rise in serum albumin and a loss of weight and the second by continued fluid retention with weight gain and no rise in serum albumin concentration. The second pattern has been observed in patients with ongoing stress such as infection. This study examines severely malnourished patients with no apparent inflammatory complications and demonstrates that this group responds to nutritional support in a pattern similar to that seen in the stressed patient. Eight patients with profound malnutrition were studied during the 1st week of nutritional support. Nitrogen balance was measured and the findings confirmed that all patients were anabolic. Sodium balances were used as an indicator of changes in the extracellular fluid compartment. Body weight and serum albumin were assessed daily. Body weight increased from 59 +/- 4 to 62 +/- 4% of normal (p less than 0.01) while serum albumin changed insignificantly (3.00 +/- 0.27 to 2.85 +/- 0.23 g/100 ml, NS) during the initial week of an adequate nutritional support regimen (nitrogen balance was +21.0 +/- 4.3 g, p less than 0.05). These changes were associated with a positive sodium balance (+215 +/- 20 mEq, p less than 0.05). These data confirm that some extremely malnourished patients do not experience a diuresis during the initial phase of nutritional support but rather may retain water and increase body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

The high carbohydrate load of total parenteral nutrition (TPN) caused a 67% increase in CO2 production which precipitated respiratory distress in the 59-year-old man reported on herein. TPN given inappropriately can serve as a physiological stress rather than nutritional support.

Nutritional depletion and repletion are associated with changes in the size of the extracellular and intracellular fluid compartments. Although the effect of nutrition on whole body composition is well established, the distribution of changes among the various body tissues is not. This study correlates changes in skeletal muscle composition with whole body electrolyte and nitrogen balance in an attempt to establish the contribution made by skeletal muscle to the changes in whole body fluid and electrolyte composition. Total parenteral nutrition was administered to ten patients for 16 to 25 days. Oxygen consumption, CO2 production, and balances of N, Na, and K were measured daily. Muscle biopsies were taken prior to administration of TPN, in the middle, and at the end of the nutritional regimen. Prior to administration of parenteral nutrition, muscle concentrations of water, sodium, and chloride were significantly higher than normal. With institution of the nutritional support regimen, all three concentrations decreased. The calculated loss in muscle water could account, at most, for only one-sixth of the loss in total body water. Muscle Na loss could account for approximately one-half of the whole body change. Potassium concentrations in the depleted patients were not significantly decreased from normal values and showed a negligible increase with TPN. Since the ratio of K to dry fat-free solids in muscle was constant, most of the whole body changes could be accounted for by assuming that nearly all N is deposited in muscle. Nutritional support results in restoration of cell mass with a contraction of the extracellular fluid (ECF) compartment. The changes in the ECF must occur in tissues other than muscle, while the restoration of cell mass occurs primarily in muscle.

Total Parenteral Nutrition (TPN) was given to 15 traumatized or infected patients with all of the non-protein calories, either as intravenous glucose (Glucose System), or as 50% glucose + 50% intravenous fat (Lipid System). Before the administration of TPN, mean urinary excretion of unconjugated norepinephrine was 2.37 +/- 0.52 (SEM) microgram/kg/day, which is significantly higher than for normal subjects (0.62 +/- 0.04 microgram/kg/day; n = 56). TPN with the Glucose System for 4-6 days significantly increased the norepinephrine excretion from 1.95 +/- 0.47 to 6.77 +/- 0.95 microgram/kg/day (P less than 0.01). When TPN with the Lipid System was given the increase (from 3.05 +/- 0.89 to 4.26 +/- 0.70 microgram/kg/day) was not statistically significant. A modest increase in resting energy expenditure was seen with the Glucose System but not with the Lipid System. The administration of high glucose loads during TPN, in addition to providing nutritional support, may exert a metabolic stress as reflected by increased metabolic rate and increased catecholamine excretion. These metabolic changes are reduced when intravenous fat emulsions are substituted for a major part of glucose calories.

Total parenteral nutrition with hypertonic glucose/AA solutions given to eighteen nutritionally depleted patients resulted in a rise in the respiratory quotient (RQ) from 0.83 to 1.05 (p less than .001), while oxygen consumption (VO2) increased only 3%. Excess glucose in depleted patients was converted to fat as evidenced by an RQ greater than 1.0. Administration of a similar glucose load to fourteen hypermetabolic patients (injury/infection) resulted in a rise in RQ from 0.76 to 0.90 while VO2 increased 29% (p less than .001) In hypermetabolic patients, even with administration of glucose in quantities above energy expenditure, there was still ongoing utilization of fat for energy, resulting in a RQ significantly less than 1.0. Excess glucose under these circumstances is apparently converted to glycogen while fat stores are utilized to partially meet energy needs. Septic and injuried man seems to preferentially utilize endogenous fat as an energy source. Administration of a large glucose load to hypermetabolic patients does not totally suppress the net fat oxidation as it does in depleted patients. Rather there is an increase in VO2, continuing oxidation of fat and apparently an increase in the conversion of glucose to glycogen.

This study examines the effect of three different hypocaloric diets on the patterns of muscle and plasma amino acids in patients undergoing total hip replacement. Group I (seven patients) received 90 g/day of glucose, Group II (seven patients) received 70 g/day of amino acids, Group III (eight patients) received both 90 g of glucose and 70 grams of amino acids per day. Utilizing the percutaneous biopsy technique of Bergström, free amino acid patterns in muscle and plasma were analyzed pre- and postoperatively (day 4). The postoperative pattern of amino acids was characterized by elevated levels in muscle and plasma of the branched chain amino acids, phenylalanine, tyrosine and methionine. There was a marked decrease in muscle glutamine and smaller decreases in the basic amino acids in both muscle and plasma. Muscle:plasma concentration ratios increased for the neutral amino acids, decreased for glutamine and the basic amino acids and were unchanged for the acidic amino acids. The patterns seen after hip replacement are almost identical to those seen after colectomy or accidental injury. There was little effect of diet on amino acid concentrations in muscle. In plasma, concentrations of leucine, isoleucine, valine and proline were higher in Group II in the absence of glucose intake, than in the other groups. Lysine was lower in Group I with no amino acid intake than in the other groups. Thus, there is a unique amino acid pattern associated with operative trauma which is relatively unaffected by hypocaloric, intravenous nutrition.

The metabolic and hormonal effect of glucose loads, ranging from 125 to 504 g/70 kg/day, were studied in severely injured patients. There was little or no correlation of glucose intake with nitrogen balance, plasma glucose, fatty acid concentrations, or epinephrine excretion. Increased norepinephrine excretion correlated with and may have resulted from increased glucose intake. Serum glucagon concentrations averaged 320 pg/ml and were not depressed by glucose intake. Insulin concentrations rose with glucose intake but were low for the level of plasma glucose. Glucose oxidation and non-oxidative metabolism, including glycogen deposition, correlated well with glucose intake. Gluconeogenesis from alanine was much higher than normal but was completely suppressed at very high intakes. The data imply that cycling of glucose, with glycerol, glycogen, or both, increased with increasing glucose intake.

Unlabelled: Lipolysis 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., Conclusions: 1) 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.

High glucose intakes given during administration of total parenteral nutrition (TPN) have been demonstrated to increase CO2 production. The workload imposed by the high CO2 production may precipitate respiratory distress in patients with compromised pulmonary function. Changes in CO2 production and O2 consumption induced by TPN using either glucose as the entire source of non-protein calories, or fat emulsions as 50 per cent of the non-protein calories, have been analyzed either in patients with chronic nutritional depletion or in acutely ill patients secondary to injury and infection. In patients with chronic nutritional depletion, shifting from the lipid to the glucose system caused a 20 per cent (P less than 0.025) increase in CO2 production which resulted in a 26 per cent increase in minute ventilation (P less than 0.01). In the acutely ill patients receiving the glucose system, CO2 production was significantly higher than in those receiving the lipid system (179 vs. 147 ml.min-1.m-2; P less than 0.01. Fat emulsions can serve as a source of non-protein calories and are associated with lesser degrees of CO2 production than isocaloric amounts of glucose.

The effect of nutritional therapy on the utilization of an intravenous fat emulsion was studied in patients with injury, infection, and nutritional depletion using I-14C-trioleate labeled Intralipid. The plasma fractional removal rate and 14C-Intralipid oxidation rate was 55% ad 25% higher, respectively, in patients following trauma and during periods of infection receiving 5% dextrose than in healthy control subjects. Total parenteral nutrition (TPN) was administered as either 1) nonprotein calories given as glucose (Glucose System) or 2) equal proportions of glucose and intravenous fat emulsion (Lipid System). In comparison to TPN with the Lipid System, administration using the Glucose System resulted in higher plasma clearance rates and lower oxidation rates in both acutely ill and depleted patients. There was no correlation between the rates of plasma removal and oxidation of the intravenous fat emulsion (r = -0.04; NS) indicating that the removal of exogenous fat from plasma cannot be used as an indicator of oxidation. A negative linear relationship was seen between the oxidation rate of intravenous fat and carbohydrate intake (r = -0.92; p less than 0.001). Glucose intakes exceeding energy expenditure did not totally inhibit oxidation of the fat emulsion. The oxidation rate of 14C-Intralipid was linearly related to net whole body fat oxidation calculated using indirect calorimetry (r = -0.90; p less than 0.001) suggesting that the fat emulsion was oxidized in a similar manner to endogenous lipids. This study suggests that intravenous fat emulsions are utilized as an energy substrate in patients with major injury, infection or nutritional depletion. This observation, along with a relative unresponsiveness to glucose in surgical patients suggests that fat emulsions may be useful as a calorie source in patients receiving parenteral nutrition.

In the United States, glucose has been until recently the sole non-protein energy substrate utilized in total parenteral nutrition (TPN). However, recent reports show that the administration of massive glucose loads to surgical patients cause a high incidence of pulmonary and hepatic complications. Indirect calorimetry data indicate that these hypermetabolic patients seem to utilize endogenous fat preferentially to carbohydrate. Therefore, we have undertaken some studies on the metabolism of endogenous and exogenous fat. Peripheral lipolysis - as estimated by measurements of glycerol turnover - is increased after injury and during sepsis. There is not correlation between the turnover of glycerol and the plasma concentration in surgical patients. High glucose intake induces a marked decrease in the glycerol turnover of nutritionally depleted subjects but has only a slight effect on the lipolytic rate of injured and septic patients. The rates of free fatty acid turnover and oxidation are elevated in surgical patients. High carbohydrate loads reduce FFA oxidation rate less in hypermetabolic patients than in depleted subjects. The utilization of exogenous fat was studied by associating an estimation of the oxidation rate to the measure of the clearance after the injection of 14C -Intralipid in surgical patients. Both oxidation and clearance rates are increased in these patients in relation with the severity of the injury. A dissociation between the variations of the clearance and the oxidation rates was observed when TPN was given to surgical patients. In such conditions, the clearance rate does not indicate the further utilization of a fat emulsion. Administration of TPN containing exogenous fat seem to induce less pulmonary and hepatic complications than TPN with glucose alone. In conclusion, kinetic measurements are needed for studying the metabolism of endogenous fat in surgical patients. An increased utilization of endogenous and exogenous fat takes place in these patients. Including exogenous fat as part of their parenteral diet is indicated but the optimal proportion of glucose and fat has not been precisely determined yet.

Previous studies have demonstrated that if isotonic amino acid infusions were administered at a rate that approximated normal daily protein requirements, a leftward shift of the minute ventilation X PaCO2 relationship occurred. This study examined the effect of the administration of parenteral nutrition, at a fixed caloric intake and two levels of nitrogen (N) intake, on the ventilatory response to CO2 in nutritionally depleted patients. The intent was to determine whether increasing protein intake from normal to twice normal requirements would result in a further enhancement of the ventilatory response to CO2. Eight patients with nutritional depletion (greater than 10% weight loss) were studied. The resting energy expenditure (REE) was measured during administration of 5% dextrose, using principles of indirect calorimetry. Each patient received parenteral nutrition for a 2-week period. Two diets were examined for a 1-week period each: 1) a high N intake-15 mg nitrogen per kcal REE (approximately 21 g/day), or b) a low N intake--7.5 mg nitrogen per kcal REE (approximately 11 g/day). The initial diet was assigned randomly. Total energy intake was set at 1.35 X REE as measured during administration of 5% dextrose solution. Nonprotein calories were administered as 50% glucose and 50% fat. Breathing patterns at rest and during inhalations of 2 and 4% CO2 were analyzed using a canopy-computer-spirometer system. With an increased nitrogen intake there was a significant reduction in resting arterial PaCO2 from 39.9 to 37.6 mmHg (P less than 0.05) with no significant change in pH.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in malnourished adult patients receiving parenteral nutrition with constant nitrogen intake and high or low glucose intakes for 8 day periods. Energy balance, nitrogen balance, weight and temperature were determined daily. Blood samples taken at admission and at the end of days 7 and 8 of each diet were analysed for glucose, fatty acids, urea, insulin, glucagon and thyroid hormones. The effect of increasing glucose intake was to increase nitrogen balance by 0.28 +/- 0.08 (SEM) mg/kJ. A scheme is proposed, based on present and previous findings, of the separate effects of nitrogen and energy intake on nitrogen balance, permitting calculation of rates of repletion of fat and lean body mass from estimates of nitrogen intake and energy balance. Malnourished patients are shown to attain markedly positive nitrogen balances at zero or negative energy balances. Large errors in estimation of energy requirements have little effect on nitrogen balance. Changes in nitrogen balance were entirely due to changes in urea excretion. Creatinine excretion increased 12% with high glucose intake, attributed mainly to increased muscle mass (7%) and body temperature (4%). A 12% increase in resting energy expenditure was only partly due to costs of glycogen storage and lipogenesis; the remainder, about one-half, is probably due to glucose and insulin mediated increases in sympathetic activity. There were marked increases in 3,5,3'-triiodothyronine (T3) concentrations with time, but no difference between the high and low glucose diets. The T3/thyroxine ratio, an index of free T3 concentration, increased much more rapidly on the high than on the low glucose diet. Changes in T3 could not account for the effect of glucose, under these conditions, to increase resting energy expenditure.

Nitrogen balance and energy expenditure were measured in 18 traumatized and/or septic patients and five depleted patients during different dietary conditions. Total parenteral nutrition (TPN) was given with nonprotein energy entirely as hypertonic glucose solutions (glucose system) or as half glucose-half intravenous fat emulsion (lipid system). In acutely ill patients, the change from 5% dextrose to TPN resulted in a prompt improvement of nitrogen balance to maintenance levels. There were no significant differences between patients given the glucose or lipid system. The five depleted patients were given the lipid and glucose systems alternately for a total of 19 one-week periods. A highly positive N balance, 80 mg N/kg . day, was attained on both diets. There was no significant difference between diets and no period of adaptation after switching from one diet to the other. On comparable intravenous diets, the acutely ill patients had higher plasma concentrations of glucose, glycerol, triglycerides, insulin, and glucagon than did the depleted patients. The study shows that the nitrogen-sparing effects of the lipid and the glucose systems are similar in moderately traumatized or infected as well as in malnourished patients. Factors other than nitrogen balance are of greater importance when choosing between the lipid and the glucose system for intravenous support.

Twenty-four-hour values for splanchnic substrate balance, O2 consumption, and CO2 production were estimated in nutritionally depleted patients, once while receiving 5% dextrose (D5W) and again after 6 or more days of glucose-based total parenteral nutrition (TPN). Nitrogen balance and whole body gas exchange were also measured. The majority of protein loss during D5W administration and the net protein synthesis during TPN occurred in the periphery. Increases in whole body and splanchnic O2 consumption occurred with TPN administration, but in both cases the splanchnic region accounted for 20% of whole body O2 consumption. Uptake of substrates by the splanchnic region was sufficient to meet splanchnic energy requirements. During TPN infusion uptake by the splanchnic region accounted for 60% of amino acids infused, whereas peripheral uptake accounted for 40%. Splanchnic uptake of glucose accounted for 20% of the glucose infused during TPN. During TPN the splanchnic region took up more glucose and amino acids than was required for energy needs and protein synthesis. It was assumed that the remainder of this substrate was used for lipogenesis. The splanchnic region accounted for 50 +/- 19% of whole body lipogenesis.

Total parenteral nutrition (TPN) using glucose as nonprotein calories was associated with increases in O2 consumption (VO2) and CO2 production (VCO2). The magnitude of the changes was a function of the patient's clinical state and glucose load. Depleted patients showed a minimal increase in VO2, while VCO2 increased 23%. Minute ventilation (VE) increased 32%. Hypermetabolic patients (major trauma, sepsis) had a 30% increase in VO2 and a 57% increase in VCO2, while VE increased 71%. Patients with mild to moderate injuries (energy expenditure +/- 15% of normal) showed a 21% increase in VO2 and a 53% increase in VCO2, while VE increased 121%. Large carbohydrate intakes were associated with increases in CO2 production in all patients, while increases in O2 consumption were seen primarily in hypermetabolic patients. These changes suggest that the high glucose loads of TPN may be a physiologic stress.

The administration of parenteral carbohydrate to nutritionally depleted patients in amounts approximating energy expenditure will markedly suppress fat oxidation. If the amount of carbohydrate is increased, net lipogenesis will occur. In contrast, it has been reported that in acutely ill, hypermetabolic patients net fat oxidation continued during the administration of glucose in quantities that exceeded energy requirements. This investigation was undertaken in an attempt to determine to what extent the latter response is due to persistent oxidation of endogenous plasma free fatty acids (FFAs) or stores of lipid in tissue. In this study, carbohydrate intake above energy equilibrium resulted in a 29% increase in CO2 production, a 2% increase in O2 consumption, and an increase in respiratory quotient (RQ) from 0.77 to 0.97 in nutritionally depleted patients. Injured and infected patients displayed a 44% increase in CO2 production and a 15% increase in O2 consumption, while the RQ increased only to 0.9. An isotopic palmitate infusion was used to measure FFA oxidation during parenteral nutrition with variable amounts of carbohydrate. Simultaneous estimates of net fat oxidation were made by indirect calorimetry. At low carbohydrate intakes, oxidation of plasma FFAs accounted for 50% of net fat oxidation in both groups of patients. Suppression of FFA oxidation was greater in the nutritionally depleted patients than in the acutely ill group at intermediate and at high carbohydrate intakes. We conclude that the continued net fat oxidation seen in acutely ill patients receiving high carbohydrate intakes is at least partially due to continuing plasma FFA oxidation. Tissue fat stores that are not in rapid equilibrium with plasma FFAs make a substantial contribution to net fat oxidation.

The experiences of the past decades have shown that critically ill patients regularly suffer marked tissue depletion. Recently, it has come to light that malnutrition may cause this depletion. The need, thus, arises for a comprehensive study of nutrition in the intensive care unit, a study relating present knowledge concerning the metabolic and catabolic states of the critically ill to possible applications in parenteral nutritional support.

A series of eight septic patients was provided varying levels of beef fibrin protein hydrolysate by central vein in the presence of adequate calories for evaluation of nitrogen retention under septic conditions. The mean nitrogen intake to achieve nitrogen equilibrium was 240 mg/kg of body wt per day. This represents a 40% increase over that required to produce nitrogen equilibrium in normal adults. The mean caloric intake of these patients was 43.3 kcal/kg of body wt per day. The calorie to nitrogen ratio based on the above intake was calculated to be 180:1. In order to utilize effectively calorie to nitrogen ratios in the nutritional care of patients, it is suggested that ratios be standardized using daily total coloric expenditures. Correcting the mean measured resting calorie expenditures of these patients for minimal daily activity, a caloric to nitrogen ratio of 138:1 was obtained. The plasma amino acid ratios in these septic patients confirm the finding that valine and phenylalnine are limiting amino acids in a beef fibrin hydrolysate at infusion levels below 240 mg of N/kg of body wt per day. Analysis of the urinary excretion of total nitrogen, urea, and amino acids in two patients suggests that 30 to 50% of the infused peptides of a beef fibrin hydrolysate are lost in the urine in these septic patients.

Malnutrition in surgical patients is associated with an increased incidence of postoperative mortality and morbidity. Preoperative nutritional support has been shown to be efficacious in reducing the incidence of these complications, although the postoperative complication rate in these patients continues to be greater than in their wellnourished counterparts. This study attempts to determine whether the postoperative course can be either influenced by or predicted from the preoperative response to nutritional support. Thirty-two patients with nutritional depletion who received an average of 1 week of total parenteral nutrition prior to a major abdominal operation were studied. These patients were followed for postoperative complications. Of the 16 patients who exhibited the characteristic response to early nutritional support, diuresis of the expanded extracellular fluid compartment with a resultant loss of weight (127.9 +/- 5.7 to 124.6 +/- 5.8 (SEM) lbs, p less than .001) and rise in serum albumin (3.21 +/- 0.14 to 3.46 +/- 0.15 gms%, p less than 0.001), only one developed a complication in the postoperative period. The other 16 patients did not exhibit this response. They retained additional fluid, gained weight (119.3 +/- 8.1 to 121.3 +/- 8.2 lbs, p less than .025), and showed a decrease in serum albumin levels (3.14 +/- 0.14 to 3.00 +/- 0.14%), p less than 0.01). Eight of these patients developed a total of 15 postoperative complications (p less than 0.01). This study demonstrates that the response to preoperative TPN is an important factor in assessing operative risk and morbidity. The need to individualize preoperative nutritional support and the timing of surgical intervention is clearly demonstrated.

Severely depleted surgical patients were given total parenteral nutrition, providing an average of 34.6 kcal and 266 mg nitrogen/kg body weight. Two diets were used, one with glucose as sole source of nonprotein energy, the other with a fat emulsion, Liposyn 10%, substituted isocalorically for one-third of the glucose. The two diets were given alternately, for 1 wk at a time, to each patient. N balance, at zero energy balance, was estimated to average 50 mg nitrogen/kg, indicating that energy intake in excess of expenditure is not required to restore lean body mass in depleted patients. Nitrogen (N) balance was equally good with either diet. Respiratory quotients and carbohydrate oxidation were lower, and fat oxidation was higher with the fat-containing diet. Amino acids and glucose were infused continuously over each 24-hr period and fat was given for only 6--8 hr. During the period of fat infusion, fat oxidation was significantly higher, and carbohydrate oxidation and RQ were lower than at other times of day.