John M. Kinney

Nutrition Support in Clinical Practice: Review of Published Data and Recommendations for Future Research Directions Summary of a Conference Sponsored by the National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition

In the last 30 years, marked advances in enteral feeding techniques, venous access, and enteral and parenteral nutrient formulations have made it possible to provide nutrition support to almost all patients. Despite the abundant medical literature and widespread use of nutritional therapy, many areas of nutrition support remain controversial. Therefore, the leadership at the National Institutes of Health, The American Society for Parenteral and Enteral Nutrition, and The American Society for Clinical Nutrition convened an advisory committee to perform a critical review of the current medical literature evaluating the clinical use of nutrition support; the goal was to assess our current body of knowledge and to identify the issues that deserve further investigation. The panel was divided into five groups to evaluate the following areas: nutrition assessment, nutrition support in patients with gastrointestinal diseases, nutrition support in wasting diseases, nutrition support in critically ill patients, and perioperative nutrition support. The findings from each group are summarized in this report. This document is not meant to establish practice guidelines for nutrition support. The use of nutritional therapy requires a careful integration of data from pertinent clinical trials, clinical expertise in the illness or injury being treated, clinical expertise in nutritional therapy, and input from the patient and his/her family. (Journal of Parenteral and Enteral Nutrition 21:133-156, 1997).

Nutrition for the patient with respiratory failure: glucose vs. fat.

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 percent 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 < 0.025) increase in CO2 production which resulted in a 26 per cent increase in minute ventilation (P < 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 < 0.01).Fat emulsions can serve as a source of non-protein colories and are associated with lesser degrees of CO2 production than isocaloric amounts of glucose.

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.

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.

Energy expenditure in surgical patients.

The metabolic and hormonal mechanisms underlying energy expenditure are reviewed, and the effects of trauma and sepsis on energy expenditure are discussed. Nutritional replacement of energy losses is also considered.

A systematic method for validation of gas exchange measurements.

The measurement of gas exchange is useful, but thus far, has not been practical during the mechanical ventilation of critically ill patients. To validate two new commercial instruments, (Siemens-Elema Servo Ventilator 900B, Beckman Metabolic Cart), the authors constructed a lung model into which they delivered CO2 and N2 at precise rates to simulate Co2 production (Vco2) and O2 consumption (Vos). The model consists of 13.5-1 gas jar with an attached one liter anesthesia bag. The lung model was ventilated at present tidal volumes and frequencies. The authors also compared the measured respiratory quotient (RQ) with the known RQ of burning methanol (RQ = 0.67) in the jar. When the model was ventilated with levels of tidal volume and gas exchange applicable to adults, both instruments measured V02 within 5 to 13% of predicted values. Varying the FI02 did not significantly affect this accuracy. At tidal volumes below 350 ml, the difference increased between predicted VCO2 and measured VCO2. The difference between measured vs. the actual RQ of methanol was 5 and 1.5% in the Siemens-Elema and Beckman Systems, respectively.

Muscle and plasma amino acids after injury: the role of inactivity.

This study is part of an investigation of whether injury is associated with a unique amino acid pattern in muscle and plasma using the total hip replacement as a model for injury. The role of inactivity is examined as a factor in producing the changes observed with injury and associated bed rest. Nineteen preoperative patients and 16 normal subjects received a muscle biopsy following an overnight fast. Blood for plasma amino acids was drawn at the time of the biopsy. Seven patients (Group I) were treated with 90 g/day of dextrose for the first four postoperative days following which a second biopsy was performed. Eight normals were placed on four days of strict bed rest. Four (Group II) received a regular diet and four (Group III) received 90 g of dextrose/day I.V. as the sole nutrient. Both Groups I and III showed increases in valine, leucine, and isoleucine in both muscle and plasma on the postoperative biopsy. The postoperative pattern differed from that observed in either group of normal subjects in that significant decreases occurred in muscle glutamine and histidine, plasma alanine, lysine and glycine. Phenylalanine, tyrosine, methionine and threonine were increased in muscle postoperatively while only phenylalanine was increased in either Group II or III of the normal subjects. Plasma phenylalanine increased in the patients while remaining unchanged in normal subjects. The pattern reported here for the patient group differs from that reported for other catabolic states (uremia, starvation, etc.), as well as inactivity with or without partial starvation. This study suggests that injury in the form of a total hip replacement is associated with a unique amino acid pattern of muscle and plasma which differs from that observed in other catabolic states. Bed rest plus partial starvation causes a pattern with certain similarities but cannot account for the postoperative changes observed.

Amino Acids and Respiration

Parenteral nutrition containing glucose and amino acids may stimulate respiration. To ascertain the effects of these solutions on respiration, eight normal subjects received an infusion of 5% dextrose (100 mL/h) for 7 days followed by an infusion of 3.5% amino acids (125 mL/h) for 24 hours. Minute ventilation (VE), tidal volume, mean inspiratory flow (VT/VI), oxygen consumption, and carbon dioxide production were significantly depressed after 7 days of 5% dextrose infusion. Ventilation and metabolic rate increased within 4 hours after initiation of the amino acid infusion and returned to normal 24 hours after the infusion. The effects of the amino acids on (VE) was secondary to an increase in (VT/VI), which is an indicator of neuromuscular ventilatory drive. Thus, within 4 hours amino acids will restore depressed metabolic rate, minute ventilation, and ventilatory drive after prolonged infusion of 5% dextrose.

Nutritional frailty, sarcopenia and falls in the elderly

Purpose of reviewThere is currently intense interest in understanding why certain elderly individuals become frail and disabled with age whereas others do not. Is frailty the result of an acceleration of normal aging processes or is it the result of chronic medical conditions that are superimposed on the conventional mechanisms of aging? The clinical problem of falls has long been recognized as a threat to some elderly individuals, but too often is not considered worthy of objective study. The factors underlying falls are now being investigated as part of the increasing attention being paid to the evolution of frailty in the elderly. Recent findingsFrailty in the elderly has been given many names, but increasing efforts are now being made to define frailty in a standardized way that would allow more objective study. The frail elderly patient usually shows loss of both neurological and muscle function. Falls in the elderly are an example in which deterioration may be present in both functions. Methods are being developed to separate the loss of muscle capacity from the associated loss of central and peripheral neurological function involved in gait and balance. SummaryThe definition of frailty has been centered around the onset of accelerated weight loss with an associated decrease of mass and strength of skeletal muscle. New studies are discussed that extend this definition. Methods for a more detailed analysis of the physiological and metabolic deficits leading to falls in the elderly may provide a better understanding of frailty in general.

A method for continuous measurement of gas exchange and expired radioactivity in acutely III patients

Abstract Many problems of current metabolic and physiologic interest could be explored if a method were available for the continuous measurement of over-all gas exchange together with the pattern of expired radioactivity following the administration of tracer amounts of labelled foodstuffs. Equipment has been designed to collect and record continuously a patients expired CO 2 O 2 , and C 14 O 2 . It is a closed system using a rigid transparent collection canopy which is practical for long runs with sick patients. Close control of temperature and pressure, with provision for internal calibration, permit ± 2 per cent system accuracy. Concentration measurements are automatically integrated; readout is in chart and printed digital form.