Whole body protein kinetics in severely septic patients. The response to glucose infusion and total parenteral nutrition.

Rates of whole body protein synthesis and catabolism in normal volunteers and in a group of severely septic patients were isotopically determined. In addition, the effect in the patients of either glucose infusion or total parenteral nutrition (TPN) on protein dynamics was assessed. The basal rate of net protein catabolism (NPC) was significantly higher in the septic patients than in the volunteers (p less than 0.05). The values obtained in the volunteers and patients were 1.44 +/- 0.18 and 2.20 +/- 0.10 g/kg/day, respectively. This increase in NPC was primarily due to a major increase in whole body catabolism that was partially counteracted by a modest increase in protein synthesis. When the patients were infused with glucose (4 mg/kg/min), NPC decreased significantly (p less than 0.001) to 1.96 +/- 0.08 g/kg/day, and during TPN the value was significantly lower again (p less than 0.04) (0.63 +/- 0.28 g/kg/day). In each instance the conservation of host tissue was due to an increase in protein synthesis: the accelerated rate of whole body protein catabolism continued irrespective of the nutritional status. The following conclusions were reached from these data: severely ill septic patients have an accelerated rate of NPC compared with normal volunteers, and this is primarily due to a large increase in whole body protein catabolism; TPN is an effective means of conserving host tissue in severely septic patients via the promotion of whole body protein synthesis; despite the beneficial effect of TPN in these patients, whole body protein catabolism continues unabated, and as a result, protein losses still occur at approximately one fourth the rate seen in the absence of TPN; and there is no obvious advantage in terms of protein-sparing when protein is provided in amounts exceeding 1.5 g/kg/day.     

Glucose intolerance in critically ill surgical patients: relationship to total parenteral nutrition and severity of illness.

The authors evaluated the relative influence of severity of illness and total parenteral nutrition (TPN) on glucose intolerance in critically ill surgical patients. Records of TPN administration, serum glucose measurements, and the simplified acute physiology score (SAPS) were extracted from the surgical intensive care unit (SICU) and hospital clinical information systems (CIS) for all patients admitted to the SICU from October 1, 1989 through March 31, 1990. Critical hyperglycemia was defined as glucose > 400 mg/dL and critical hypoglycemia as < 40 mg/dL. During the study period, 1,129 patients received 3,054 days of care, including 88 patients who received 705 days of TPN. Of 4,985 glucose determinations performed during the study period, 48 (0.96%) were critically abnormal. Critical hyperglycemia occurred in 1.7 per cent of blood samples from TPN patients, compared to 0.7 per cent in non-TPN patients (P < 0.005). However, the mean admission and daily and maximum severity of illness scores were significantly higher in TPN patients compared to non-TPN patients (all P < 0.0005). Mean glucose levels rose with increasing SAPS in both TPN and non-TPN patients. When stratified by severity of illness, TPN patients did not have significantly higher glucose levels than non-TPN patients except for the SAPS = 15 category. The authors conclude that the glucose intolerance noted in critically ill TPN patients reflects their underlying severity of illness rather than TPN administration per se.     

Hunterian Lecture: Insulin resistance in human sepsis: implications for the nutritional and metabolic care of the critically ill surgical patient

Loss of the anabolic effect of insulin (insulin resistance) is a key component of the adverse metabolic consequences of sepsis and may contribute to the apparent lack of efficacy of feeding regimens in critically ill patients. The mechanisms which underlie the development of insulin resistance in stress remain unclear. In this series of studies, the locus of insulin resistance in the septic patient was shown to lie within the metabolic pathways of glucose storage (glycogen synthesis) within skeletal muscle, was noted to be unrelated to the actions of hormone mediators such as leptin and was shown not to be associated with altered nutrient-induced thermogenesis during total parenteral nutrition (TPN). Clinically applicable maximal rates of glucose-based TPN for septic patients were calculated. A technique was also developed in which insulin resistance could be induced and studied in healthy volunteers. These studies demonstrated that insulin resistance develops within 7 h of an inflammatory stimulus and, as in clinical sepsis, is characterised by selective impairment of glucose storage. Finally, a series of related studies indicated that the magnitude and nature of the inflammatory response in vivo could be enhanced by exogenous insulin infusion, indicating links between the hormone systems involved in intermediary metabolism and the inflammatory response. These findings have significant implications for the optimal design of feeding regimens for critically ill patients.     

Hypocaloric Support in the Critically Ill

The critically ill patient exhibits a well defined endocrine and metabolic adaptive response to stressor agents, characterized by incremented resting energy expenditure (hypermetabolism, which is believed to signify increased energy requirements), accelerated whole-body proteolysis (hypercatabolism), and lipolysis. These phenomena occur in the acute stage, which is also characterized by hyperglycemia, typically accompanied by a hyperdynamic cardiovascular reaction manifested by high cardiac output, increased oxygen consumption, high body temperature, and decrease peripheral vascular resistance. High provisions of glucose-derived calories tend to accentuate these reactions and increase the degree of hyperglycemia. We have adopted a hypocaloric-hyperproteic regimen which is provided only during the first days of the flow phase of the adaptive response to injury, sepsis, or critical illness. Our regimen includes a daily supply of 100 to 200 g of glucose and 1.5 to 2.0 g of protein (synthetic amino acids) per kilogram of ideal body weight. We have analyzed the data on 107 critically ill patients, 70 men and 37 women, who were admitted to the surgical intensive care unit and who received nutritional support by the TPN hypocaloric modality for a minimum of 3 days. We found that the high caloric loads contained in TPN regimens results in additional metabolic stress, with consequent hyperdynamic cardiorespiratory repercussion, high CO₂ production, and frequently hepatic steatosis. In contrast, our hypocaloric-hyperproteic approach has resulted in a more physiologic clinical course and considerable reduction in cost. The infusion of high glucose loads, such as those used in hypercaloric TPN, does not seem to suppress the excessive endogenous production of glucose but instead markedly exacerbates the hyperglycemia of the postinjury and acute stress condition. We believe that the hypocaloric-hyperproteic regimen we utilize during the first few days of the stress situation is more in accordance with the inflammatory and hormonal mediator climate of the initial stages of the flow phase and thus appears to be beneficial vis-à-vis the hypercaloric loads that many use as routine metabolic support in critically ill patients.     

An integrated analysis of glucose, fat, and protein metabolism in severely traumatized patients. Studies in the basal state and the response to total parenteral nutrition.

A series of isotopic infusions were performed in 43 severely ill patients suffering from blunt trauma (mean injury severity score of 31). The patient data have been compared with data obtained from 32 normal volunteers, and in addition the metabolic response of the trauma patient to total nutritional support (TPN) has been assessed. The rate of VO2 was elevated in the trauma patients compared with that of the volunteers (160 mumol/kg/minute vs. 103 mumol/kg/minute). Glucose production was significantly increased in the patients compared with the volunteers (21 +/- 2 mumol/kg/minute vs. 14 +/- 1 mumol/kg/minute), but the trauma patients had an impaired capacity to directly oxidize plasma glucose. The percentage of glucose uptake oxidized in the volunteers was 36 +/- 2%, and the percentage of glucose uptake recycled was 10 +/- 1%. By contrast, in the trauma patients, 23 +/- 4% of the glucose uptake was directly oxidized, and 29 +/- 11% was recycled. The rate of glycerol turnover in the trauma patients (5.3 +/- 0.3 mumol/kg/minute) was significantly elevated compared with the volunteer value (2.2 +/- 0.1 mumol/kg/minute), and the basal rate of fat oxidation was twice as high in the patients as in the volunteers (2 mg/kg/minute vs. 1 mg/kg/minute). The rate of whole body protein catabolism was significantly higher in the patients (5.8 +/- 0.7 g/kg/day vs. 4.3 +/- 0.3 g/kg/day), and as a result, the rate of net protein catabolism was significantly elevated in the patients. The response to TPN (amino acids and a 50:50 mixture of glucose and fat) included an increase in the percentage of glucose uptake oxidized (up to 45 +/- 12%), a decrease in the oxidation of fat (up to 0.8 mg/kg/minute), and a significant increase in whole body protein synthesis (up to 6.1 +/- 1.1 g/kg/day) so that the rate of net protein loss was minimized but not prevented. (The rate of net protein catabolism during TPN was 1.3 +/- 0.5 g/kg/day.) There was no correlation between the injury severity score (ISS) and the degree of metabolic abnormality. The rate of NPC in the patients with ISS less than 20 was higher than in the volunteers (ISS = 0), but the values for NPC in patients with ISS 21-40, and ISS greater than 40 were virtually identical to the corresponding values in patients with ISS less than 20. It is concluded from these studies that: 1) Trauma patients have a high rate of VO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Free fatty acid mobilization and oxidation during total parenteral nutrition in trauma and infection.

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 rate and route of nutrient intake on protein metabolism

Isotopic measurements of protein kinetics are useful for the investigation of metabolic protein disorders during surgical illness. The effects of rate and route (oral vs parenteral) of nutritional substrate intake have not been well defined. Fischer 344 rats were infused with a total parenteral nutrition (TPN) solution at either 25, 100, or 175% of their normal substrate intake or were fed an oral diet ad libitum. After 4 days, [15N]glycine was infused at 0.138 mg 15N/hr for 24 hr. Whole-body protein turnover (WPT), synthesis, and catabolism were determined by 15N urea enrichment. Fractional synthesis rates (FSR) of liver and muscle protein were calculated by analyzing 15N tissue enrichment. WPT (r = 0.93, P less than 0.001) and liver FSR (r = 0.57, P less than 0.01) increased linearly with TPN infusion rates. All rats had protein synthesis rates greater than catabolism rates except for the rats infused with 25% TPN. Although caloric intake was the same in rats fed orally and those infused with 100% TPN, the orally fed rats had faster WPT (P less than 0.001), synthesis (P less than 0.05), catabolism (P less than 0.001), and liver FSR (P less than 0.05) than the TPN rats. Muscle FSR was not significantly affected by either the route of feeding or the TPN infusion rate. In this study, rate and route of substrate intake affected protein kinetics in the whole animal and liver, but not in muscle. Rate and route of nutrient intake need to be carefully specified and controlled during isotopic studies of protein kinetics.     

Whole body protein turnover, synthesis and breakdown in patients receiving total parenteral nutrition (TPN) before and after recovery from surgical stress

This study was conducted to clarify the mechanisms underlying the loss of body nitrogen after trauma. Six patients who underwent abdominal surgery and six for control were studied. The measurement of whole body protein turnover was made on the third and tenth postoperative day during TPN with constant infusion of [15N] glycine according to Picou and Taylor-Roberts. The measurement was also made on six control patients during TPN in non-stressed state. The rates of whole body protein turnover (Q), synthesis (S) and breakdown (B) were calculated from the plateau 15N enrichment of urinary total N, which was analyzed with a mass spectrometer. The values were compared with control and the changes in the individual patients were examined by a paired t-test. Immediately after operation, Q and B were significantly elevated (p less than 0.05 and p less than 0.02, respectively), and reduced with the improvement of N-balance after recovery from stress by 0.95 +/- 0.21 and 0.61 +/- 0.13 g X protein/kg X day, respectively. The changes in Q and B were statistically significant (p less than 0.005 and p less than 0.005, respectively). Whereas, no tendency of alteration in S was found throughout the study. It is concluded that protein turnover rate increases in surgical stress, and that the increased protein catabolism rather than the alteration in synthesis could account for the postoperative nitrogen losses.     

Metabolic treatment of critically ill patients: energy balance and substrate disposal

Oxidation of substrates is the main biochemical process used by the human body to produce energy. Different substrates (carbohydrates, lipids, and proteins) have different effects on oxygen consumption and carbon dioxide production: during the critical phase of pathologies it could be relevant pay attention to the use of various nutrients, that have some altered effect respect to the normal subjects metabolism, and during the length of metabolic treatment, too. Generally, nutrition lead to replenish body stores, while endogenous substrates are used to be oxidized. Critically ill patients show a preference for prompt energy availability (i.e. glucose) to avoid endogenous protein catabolism; lipids are shown to have a more pronounced storage effect. Adequate amount of energy intake in carbohydrates determine an increase of RQ, that means a shift from a more lipid-based to a more glucose-based oxidation. Composition of dietary intake can be usefully different for each pathology, and also for different periods of the same pathology, because critically ill patients have a variety of metabolic needs during their stay in ICU.     

Anabolic effects of oxandrolone after severe burn

OBJECTIVE: To explore the hypothesis that oxandrolone may reverse muscle catabolism in cachectic, critically ill pediatric burn patients. SUMMARY BACKGROUND DATA: Severe burn causes exaggerated muscle protein catabolism, contributing to weakness and delayed healing. Oxandrolone is an anabolic steroid that has been used in cachectic hepatitis and AIDS patients. METHODS: Fourteen severely burned children were enrolled during a 5-month period in a prospective cohort analytic study. There was a prolonged delay in the arrival of these patients to the burn unit for definitive care. This neglect of skin grafting and nutritional support resulted in critically ill children with significant malnutrition. On arrival, all patients underwent excision and skin grafting and received similar clinical care. Subjects were studied 5 to 7 days after admission, and again after 1 week of oxandrolone treatment at 0.1 mg/kg by mouth twice daily or no pharmacologic treatment. Muscle protein kinetics were derived from femoral arterial and venous blood samples and vastus lateralis muscle biopsies during a stable isotope infusion. RESULTS: Control and oxandrolone subjects were similar in age, weight, and percentage of body surface area burned. Muscle protein net balance decreased in controls and improved in the oxandrolone group. The improvement in the oxandrolone group was associated with increased protein synthesis efficiency. Muscle protein breakdown was unchanged. CONCLUSIONS: In burn victims, oxandrolone improves muscle protein metabolism through enhanced protein synthesis efficiency. These findings suggest the efficacy of oxandrolone in impeding muscle protein catabolism in cachectic, critically injured children.     

Whole-body protein kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion and total parenteral nutrition

We have isotopically determined rates of whole-body protein synthesis and catabolism in a group of normal volunteers and in two groups of cancer patients: 20 patients with advanced weight-loss (AWL) upper gastrointestinal cancer and 7 patients with early non-weight-loss (ENWL) lower gastrointestinal cancer. In both patients and volunteers we determined protein kinetics in the basal state and during glucose infusion at 4 mg/kg/min. In addition, in the AWL patients the effect of total parenteral nutrition (TPN) on protein dynamics was also assessed. The rate of net protein breakdown was determined with the primed constant infusion of either 15N-urea or 14C-urea, the rate of whole-body protein catabolism was measured with the primed constant infusion of 15N-lysine, and the rate of whole-body protein synthesis was deduced from the above two values. The basal rates of net protein catabolism, whole-body protein catabolism, and whole-body protein synthesis were similar in the volunteers and ENWL cancer patients. The basal values for net protein catabolism in the volunteers and ENWL patients were 1.46 +/- 0.18 and 1.34 +/- 0.08 gm/kg/min, respectively. In both volunteers and ENWL patients glucose infusion resulted in a significant decrease in net protein catabolism. In the ENWL patients this decrease was due to a significant decrease in whole-body protein catabolism (p less than 0.05); the rate of whole-body protein synthesis did not change significantly. In the AWL cancer patients the rate of net protein catabolism was significantly higher than in either the volunteer or ENWL group (p less than 0.05), and glucose infusion did not result in a decrease in net protein catabolism. However, when the AWL group was studied during TPN there was a significant decrease in net protein catabolism from 2.24 +/- 0.30 to 0.17 +/- 0.09 gm/kg/day (p less than 0.01). This decrease was due to the combined effect of a significant decrease in whole-body protein catabolism coupled with an increase in whole-body protein synthesis. From these studies we conclude the following: (1) ENWL cancer patients and normal volunteers have similar protein dynamics, and in both groups glucose infusion resulted in a significant decrease in protein loss. (2) AWL cancer patients have an elevated rate of net protein catabolism, and this is not sensitive to glucose infusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical evaluation of a '3-in-1' intravenous nutrient solution

Eighty-five consecutive general hospital patients requiring total parenteral nutrition (TPN) were prospectively studied in order to evaluate the safety and efficacy of a '3-in-1' nutrient mixture. All formulas were individualized to estimated requirements (average composition nitrogen 14 g, glucose 350 g, fat 50 g), mixed in the hospital pharmacy, contained within 3-litre EVA plastic bags, and given to the patients as a continuous 24-hour infusion. The average duration of TPN was 19 days per patient (range 8 - 84 days). Judging by nitrogen balance and plasma protein concentrations, the system was effective in maintaining or improving nutritional status in patients in a relatively stable condition but not in those who were critically ill (e.g. those in an intensive care unit). Development of magnesium and iron deficiencies was common during the period of TPN (25% of patients developing magnesium deficiency and 40% developing iron deficiency) despite daily supplementation with commercial trace element mixtures, but these states were easily corrected by high-dose administration. 'Creaming' of less than 5 mm on the surface of the emulsion was common, whereas that of more than 10 mm was rare (12 bags) and invariably associated with excessive addition of polyvalent cation or glucose. Deposition of lipid on the internal surface of the catheter was a common problem after 2 weeks' continuous administration. Temporary problems with faulty bag connections resulted in excessive catheter sepsis (14%) due to Staphylococcus epidermidis. Mild reversible disturbances in liver function occurred in one-third of the patients. The system appears safe and effective for the management of most patients requiring long-term TPN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sepsis from triple- vs single-lumen catheters during total parenteral nutrition in surgical or critically ill patients

We prospectively studied the infection rates for 59 triple-lumen (TLC) and 68 single-lumen (SLC) subclavian catheters during the administration of total parenteral nutrition (TPN) to surgical or critically ill patients. A standard protocol was used for catheter insertion and maintenance. The infection control committee determined independently whether patients had catheter-related sepsis, an infected insertion site only, or no catheter infection. The TLCs had an increased incidence of catheter sepsis (19%) compared with the SLCs (3%). Low rates (5% for TLCs and 3% for SLCs) of infected catheter sites only indicated that the catheter care was comparable for both groups. The patients in the two groups were similar but not identical; those with TLCs appeared to be sicker and, therefore, at greater risk to develop catheter sepsis than patients with SLC. However, since TLCs were involved in six times more catheter sepsis than were SLCs, limiting the use of a subclavian catheter to giving TPN only and strict adherence to a TPN protocol are necessary to minimize the risk of catheter sepsis.     

The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol

Total parenteral nutrition (TPN) after trauma and sepsis has two major goals. One is the reduction of enhanced protein catabolism; the second is the avoidance of enhancement of whole-body glucose turnover. Glucose and xylitol differ in their quantitative utilization rate after trauma and sepsis. Maximal glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects with regard to whole-body glucose turnover rate of gluconeogenesis and protein sparing, we conducted two studies using animal models and two clinical studies. METHODS. For the determination of glucose and protein turnover, radioactive and stable isotope techniques were applied. In an animal model a primed constant infusion of 3-H-6-glucose, 14-C-1-alanine and 13-C-3-alanine and 14-C-U-acetate was used to determine total glucose appearance, gluconeogenesis from 3-C-precursors and alanine flux. In the human studies hepatic glucose production was determined by using a primed constant infusion of 6.6-D-2-glucose and urea synthesis rate was determined by a primed constant infusion of 2-N-15-urea. RESULTS. In the first rat model we were able to show that hypocaloric xylitol compared to glucose significantly reduced whole-body glucose turnover from 1741 +/- 232 mumol/h during glucose infusion to 449 +/- 49 mumol/h during xylitol infusion and gluconeogenesis from C-3 carbons form 382 +/- 24 mumol/h during glucose infusion to 155 +/- 39 mumol/h during xylitol infusion after a burn trauma. In a second septic rat model the exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated N-balance from +144 +/- 90 mgN/kg body weight per day during glucose infusion to +699 +/- 80 mgN/kg body weight per day during glucose-xylitol infusion and a reduced 3-methyl-histidine excretion from 7.14 +/- 0.61 mumol/kg body wt. per day during glucose infusion to 4.10 +/- 0.56 mumol/kg per day during glucose-xylitol infusion, respectively. In two studies with surgical intensive care patients we were able to confirm the nitrogen-sparing properties of xylitol infusion, together with amino acids during hypocaloric feeding or during TPN with a glucose/xylitol mixture in a proportion of 1:1. From a basal urea production rate of 9.2 +/- 1.6 mumol/kg min. xylitol led to a significant reduction with 6.4 +/- 1.5 mumol/kg per min. Hepatic glucose production was significantly reduced during xylitol infusion from basal 4.8 +/- 0.6 mg/kg per min to 3.1 +/- 0.7 mg/kg per min, respectively. Equicaloric glucose in a dosage of 3 g/kg per day had no effect. During TPN glucose/xylitol, in a proportion of 1:1 at a total dosage of 0.24 g/kg per h, significantly reduced whole-body glucose turnover, endogenous glucose production and lactate concentrations compared to an isocaloric glucose infusion. DISCUSSION. In animal as well as in human studies hypocaloric xylitol as well as a glucose-xylitol mixture were more efficient in preserving body protein than glucose alone. Whole-body glucose turnover was significantly reduced during hypocaloric xylitol or glucose-xylitol infusion compared to isocaloric glucose infusion. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg body wt. per day using xylitol. During long-term TPN, a glucose-xylitol mixture in a proportion of 1:1 in a dosage of 3 g/kg body wt. per day each is recommended as energy source, together with amino acids and, if necessary, lipids.     

Whole body protein synthesis and turnover in normal man and malnourished patients with and without known cancer.

Plateau enrichment of 15N-ammonia following 24 hour continuous intravenous infusion of 15N-glycine was used to measure total body protein turnover and synthesis in normal volunteers and malnourished patients, with and without cancer. The mean postabsorptive total body protein synthesis rate in three normal controls was 2.5 g protein/kg/day. Protein synthesis and turnover decreased by a mean of 23% following one week of fasting, and returned to baseline levels following one week of refeeding. In three malnourished patients without known tumor, whole body protein synthesis and turnover was similar to controls; following seven to ten days of total parenteral nutrition (TPN) in the nontumor-bearing patients whole body protein synthesis and turnover decreased by 18%. Three of seven malnourished patients with known tumors had marked elevations in total body protein synthesis and turnover; TPN increased protein turnover in five of seven patients with known cancer. This study suggests that some malignant tumors can increase whole body protein synthesis and turnover in both the malnourished and fed state. This increase in protein turnover may represent a direct effect of the tumor, or reflect concomitant illness.     

Metabolic utilization of intravenous fat emulsion during total parenteral nutrition

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.     

Sequential Metabolic Changes following Induction of Systemic Inflammatory Response in Patients with Severe Sepsis or Major Blunt Trauma

We have recently completed studies in critically ill patients with severe sepsis or major trauma that investigated sequential changes in the metabolic response following admission to the intensive care unit. Protein, water, and energy metabolism were measured using in vivo neutron activation analysis, tracer dilution, dual-energy x-ray absorptiometry, and indirect calorimetry. Over the 3-week study period both groups of patients lost 13% of their total body protein. The severe sepsis patients retained twice the volume of fluid of those with major trauma, and the return to normal hydration in the sepsis group was correspondingly prolonged, especially for those in the elderly age group. In both groups of patients resting energy expenditure increased progressively over the first week to around 40% above normal and was still elevated 3 weeks from onset of illness. A twofold increase in total energy expenditure occurred in both groups of patients between the first and second weeks of critical care admission. The prolonged hypermetabolism throughout the study period was not reflected in the concentrations of circulating proinflammatory cytokines, which fell rapidly over the first week. The pattern of changes seen in plasma proinflammatory and antiinflammatory cytokine concentrations is similar for sepsis and trauma. The remarkably similar metabolic sequelae seen in critically ill patients following the onset of severe sepsis or major trauma may constitute a universal response to the induction of the systemic inflammatory response syndrome.     

A prospective randomized study of the optimal source of nonprotein calories in total parenteral nutrition

We previously showed that providing 30% of nonprotein calories as lipid eliminated glucose intolerance and ameliorated the other troublesome metabolic complications of total parenteral nutrition (TPN): hepatic abnormalities and hypertriglyceridemia. Whether such a mixed-fuel system is as effective as a hypertonic glucose-only TPN fuel system in achieving an anabolic state was tested in 88 consenting patients randomized to either conventional TPN (25% dextrose and 4.25% amino acids) or modified TPN (15% dextrose, fat, and 5% amino acids). Treatment groups were: group A, no surgery, TPN only; group B, postoperative TPN starting 48 hours after surgery; and group C, preoperative TPN, surgery on day 7 and with continued postoperative TPN. In all groups TPN was given for 14 days while patients were given nothing by mouth. Changes in the indexes of body protein metabolism, reflected by nitrogen balance, serum albumin, blood urea nitrogen, and weight, were measured on days 1 and 14. Nitrogen balance improved in patients randomized to either regimen, but there was no significant difference in the degree of improvement. Albumin levels were maintained, and differences between initial and final values were not significant. Blood urea nitrogen increased in all groups (p less than 0.05); however there was no significant difference between regimens. Patients maintained their weight, and fluid balance data indicated no water retention. Observed weight changes were not statistically significant. In each treatment group an anabolic state occurred and gains in measured protein indexes were similar. Isocaloric replacement of 30% of TPN glucose calories with fat was as effective as glucose-only TPN in achieving an anabolic state without the metabolic complications associated with glucose-only TPN.     

A controlled, randomized trial evaluating the effects of enteral and parenteral nutrition on protein metabolism in cancer-bearing man

To characterize the effects of enteral versus parenteral nutritional support on protein metabolism in the cancer patient, patients with localized, squamous cell carcinoma of the distal esophagus were randomized to receive nutritional support as follows: (1) if there was a loss of less than 20% of the preillness body weight, patients were randomized to continue eating ad libitum (group I) versus receiving total parenteral nutrition (TPN) (group II); (2) if there was a loss greater than 20% of the preillness body weight and/or the patient was unable to swallow, patients were randomized to jejunostomy feedings (group III) versus TPN (group IV). Patients were initially studied in the postabsorptive state and again 2 weeks after beginning, and while receiving, enteral or parenteral feedings. Stable isotopic tracer methods utilizing constant infusion of [15N]glycine were used to determine whole-body protein turnover (flux), synthesis, and catabolism. Skeletal muscle catabolism was determined by measuring the urinary excretion of 3-methylhistidine and lean tissue mass was evaluated by determining total-body potassium by 40K whole-body scanning. Positive nitrogen balance was obtained in groups II and IV associated with significant weight gain in both; the changes in weight were not significant in groups I and III. Whole-body protein flux increased in all groups, but significantly only in group II. Synthesis increased in groups II and IV and decreased in I and III, but not significantly. Catabolism tended to decrease in all groups but group I. Urinary 3-methylhistidine excretion decreased in groups II and IV signifying decreased skeletal muscle catabolism, but increased in groups I and III. Total body potassium tended to increase in groups II and IV. In this group of patients with localized squamous cell carcinoma of the esophagus, both TPN and jejunal feedings tended to stabilize nutritional status and whole-body protein economics. TPN appeared to be slightly more efficacious, although the differences between enteral and parenteral nutritional support in this study were slight.     

Do multi-lumen catheters increase central venous catheter sepsis compared to single-lumen catheters?

Triple-lumen catheters (TLC) are now routinely used in critically ill and multiply injured patients who require multi-port central venous access. An apparent rise in catheter contamination and catheter-related sepsis (CRS) occurred in patients receiving total parenteral nutrition (TPN) through a TLC as opposed to a single-lumen catheter (SLC). A prospective study was performed to determine rates of catheter contamination and CRS in multiple trauma and general surgical-medical patients who received TPN through TLC's and SLC's. Three hundred seven TLC's and 68 SLC's were placed in 234 patients during a 12-month period. There was no statistically significant difference in the rate of contamination or CRS between the two groups although there was a trend toward increased CRS and contamination in the TLC group. TLC's may be used for short-term administration of TPN without significant increase in catheter contamination or CRS.