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

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

Parenteral nutrition in septic patients: effect of increasing nitrogen intake.

Metabolic effects of increasing nitrogen intake during total parenteral nutrition (TPN) were studied in nine septic patients. The patients were given 5% dextrose (D5W) for 1 d. For the next 6 d they received total parenteral nutrition (TPN), at 1.35 times resting energy expenditure (REE), containing either 191 or 366 mg N/(kg.d) Non-protein calories were divided equally between glucose and lipid emulsion. Three patients were studied on both diets (n = 6 for each diet). On the high- but not the low-N diet were significant increases in protein oxidation, blood urea N, O2 consumption, and CO2 production. TPN normalized most plasma amino acid levels but intramuscular amino acids remained unchanged. Transient positive N balance occurred during days 1-3 on the high- but not the low-N intake; on days 5-6 N balance did not differ significantly from zero on either diet and the improvement (165 mg N/[kg.d]) was the same for both diets.

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

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

Changes in nitrogen balance of depleted patients with increasing infusions of glucose.

Depleted patients were maintained on intravenous infusions of amino acids and glucose with constant N intake (173 mg/kg body weight), and three different levels of energy intake (15.4, 37.6, and 58.5 kcal/kg) given sequentially for 4 days each. Changes in N balance were abrupt and maximal in 1 to 2 days. Maximal changes in N balance preceded, and were not dependent on maximal changes in fat and glucose metabolism. N retention increased 1.7 mg/kcal of increased energy balance, during both hypocaloric and hypercaloric intakes, a value similar to that observed in normal adults. No increase in resting energy expenditure occurred with increasing energy intake during negative energy balance. During positive energy balance resting energy expenditure increased by 1 kcal for each 5 of intake. It seems likely that increasing energy restores mainly that portion of lean body mass associated with fat deposition; and rapid restoration of lean body mass requires high N intakes. At zero energy balance, N balance in these depleted patients was only slightly positive at an intake of 173 mg N per kilogram. This is about twice the intake of N required to maintain zero N balance in normal adults.

Effects of increasing nitrogen intake on nitrogen balance and energy expenditure in nutritionally depleted adult patients receiving parenteral nutrition.

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.

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

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

The energy expenditure of the mechanically ventilated critically ill patient. An analysis.

This study characterizes the pattern of caloric expenditure of a group of 19 mechanically ventilated critically ill patients after surgery. Continuous measurements of metabolic rate were used to examine the total energy expended over an eight-hour period (10 AM to 6 PM) on 21 occassions. This allowed for determination of the energy expended during activity, rest, and sleep. The patients were observed to be resting, defined as lying motionless with eyes open and responsive to surrounding events, for 44 +/- 4 percent (SE) of the studied period. Sleeping, a state where the patient was not aroused by surrounding events, was observed for 17 +/- 3 percent of the studied period. Total energy expenditure was 4.8 +/- 1.8 percent greater than resting energy expenditure (REE). The REE was 13.1 +/- 2.3 percent above sleeping energy expenditure (awakeness factor), while activity energy expenditure was 17.1 +/- 2.9 percent above REE (activity factor). The respiratory quotient (RQ) during activity in the 15 patients receiving infusions of physiologic saline solution or 5 percent dextrose solution was significantly less (p less than 0.02) than the RQ during rest. This appears to be due to increased fat oxidation during activity.

Respiratory distress secondary to a high carbohydrate load: a case report.

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.

Carnitine metabolism during fasting in dogs.

During starvation, a series of changes in whole body fuel use occur that result in conservation of fuel, particularly protein. Use of fat stores for ketone production and direct oxidation of fat as a primary fuel are characteristic of starvation. However, the mechanism by which this change develops is unclear. Carnitine is an important compound in the control of fat metabolism, since long-chain free fatty acids must be coupled with it to cross the mitochondrial membrane. This study attempts to define, in the fasting dog model, the interaction between plasma and muscle carnitine, its acyl esters, and the energy substrates available. Eight adult beagle dogs were studied during an 8-day period of starvation. Muscle and plasma were analyzed for free carnitine (FC), acid-soluble fraction, and long-chain esters (LCE), as well as substrate hormone profiles. Total carnitine (TC) and short-chain esters (SCE) were calculated. Muscle was analyzed for carnitine palmityl transferase activity (CPT). These measurements were performed on days 3, 5, and 8. There was a significant (p less than 0.05) loss in weight on days 3, 5, and 8. TC and FC increased significantly (p less 0.05) only on day 8; this occurred simultaneously with a significant (p less than 0.05) decrease in CPT. It was preceded by a significant (p less than 0.05) and persistent increase in plasma TC, FC, and LCE that developed on day 3. During starvation there was an increase in plasma carnitine levels before changes in muscle. The increase in muscle carnitine occurred between days 5 and 8 of starvation and seemed to be associated with a fall in CPT. This may be responsible either for or secondary to the decrease in metabolic rate that occurs during prolonged starvation.

Energy expenditure, nitrogen balance, and norepinephrine excretion after injury.

In this study we examine the effect of different hypocaloric nutritional regimens on nitrogen balance in patients following total hip replacement and compare it to that of normal subjects on strict bed rest. The interrelationship between nitrogen balance, energy expenditure, and urinary free norepinephrine excretion is analyzed with emphasis on the effects of nutrition on these relationships. Amino acid infusions following major elective orthopedic surgery had no nitrogen-sparing effect above that of 5% dextrose. Optimum nitrogen balance was obtained by administration of both 5% dextose and 3.5% amino acids. Patients receiving 5% dextrose showed no increase in resting energy expenditure in postoperative period compared to the preoperative control value. However, patients receiving amino acid infusions showed a 14% rise in energy expenditure postoperatively. Failure to administer 5% dextrose was associated with a high urinary norepinephrine excretion postoperatively. In normal subjects on bed rest either 5% dextrose or total starvation resulted in a marked fall in resting energy expenditure, whereas amino acid infusions isocaloric to the carbohydrate intake prevented any fall in resting energy expenditure. Nitrogen balance was improved with amino acid infusions in normal subjects. This study suggests the effect of amino acid infusions is highly dependent on the metabolic state of the patient.

Metabolic and endocrine effects of fasting followed by infusion of five-percent glucose.

Isotonic glucose is often the sole nutrient provided to hospitalized patients with varying degrees of protein calorie malnutrition. To study the effects of such diets uncomplicated by illness, normal human subjects were fasted (6 to 14 days) before receiving an infusion of 5% dextrose (5 to 7 days). Norepinephrine excretion rose steadily-to six times control values-during the first 6 days of the fast and changed little thereafter. It remained high during the first 3 days of glucose infusion and subsequently returned toward normal. The rate of NTau-methylhistidine excretion changed little during the fast but decreased abruptly with glucose infusion. The magnitude of NTau-methylhistidine excretion indicated that undirectional muscle protein degradation was about equal to nitrogen excretion during the fast, and that the decrease in muscle protein degradation could account for the abrupt decrease in nitrogen excretion (from 91 to 30 mg N/kg . day) after glucose infusion. This suggests that the conservation of muscle protein caused by glucose infusion in this setting is affected by decreased degradation rather than by increased synthesis. Changes in NTau-methylhistidine excretion and total nitrogen excretion were more rapid than, and therefore not mediated by, changes in insulin concentration or norepinephrine excretion.

Influence of parenteral carbohydrate on fat oxidation in surgical patients.

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 effect of carbohydrate intake on the lipolytic rate in depleted patients.

The effect of intravenous carbohydrate intake on glycerol turnover and fat metabolism was estimated in six nutritionally depleted surgical patients requiring total parenteral nutrition. Two diets were given. Nitrogen intake was the same in both diets. The calorie intake, adjusted by varying glucose intake, provided either 72% or 128% of the measured resting energy expenditure. Glycerol turnover was measured during administration of 5% dextrose solutions before starting total parenteral nutrition, and again after 4 days on each diet. Turnover rates of glycerol were closely correlated with plasma concentrations. However, fractional turnover rates were only two-thirds of normal values, indicating decreased clearance possibly due to decreased hepatic blood flow. Glycerol turnover, plasma free fatty acid concentrations, and rate of fat oxidation declined progressively with increased glucose intake. When compared with these results, previous studies of injured and septic patients showed: higher values for glycerol turnover, FFA concentrations, and fat oxidation; poor corrlation between glycerol turnover and concentration; inhibition of lipogenesis at high glucose intake; and high rates of norepinephrine excretion. The data suggest that in severe injury, counter regulatory hormones may almost completely block the effects of insulin on hormone sensitive lipase but have less influence on insulin stimulation of FFA esterification and inhibition of ketone body synthesis.

Protein and energy sparing of glucose added in hypocaloric amounts to peripheral infusions of amino acids.

After abdominal surgery, patients were given peripheral infusions of amino acids alone for 4 days followed by amino acids plus glucose for 4 days, or the same solutions in the reverse order. Although there was a wide variation in the response of individual subjects, the typical effect of glucose under these conditions was to reduce both nitrogen excretion (average of 2.8 g N/day) and resting metabolic expenditure (average of 110 kcal/day).

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

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

Some metabolic effects of fat infusions in depleted patients.

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.

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

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

The effects of varying energy and nitrogen intake on nitrogen balance, body composition, and metabolic rate.

Body protein content (as measured by N balance) is normally regulated at a constant level, but is influenced by the level of both energy and N intake. Energy and N act synergistically on N balance. Not all forms of energy are equally effective in maintaining zero N balance; approximately 500 kcal of carbohydrate are required daily by the brain, and this minimum amount of dietary carbohydrate cannot be replaced by fat without loss of body N. Acute illness is accompanied by a catabolic state and an increase in the minimum N intake required for zero N balance. Nutritional depletion induces a metabolic state similar to that typical of growing organisms, in that N can be retained at zero energy balance. BMR includes essential thermogenesis and facultative thermogenesis. In addition, food has a specific dynamic action; it increases metabolic rate. Nutrient-induced increases in metabolic rate are exaggerated in acutely ill patients, such that large amounts of IV glucose may constitute a metabolic stress when given to patients. Equivalent N sparing can be obtained when as much as half of the glucose calories are replaced by fat calories. N balance is an incomplete index of nutritional status, and important information may be gained from measurements of body composition of acutely ill patients; in particular, the degree of expansion of ECW may predict outcome.

Muscle and plasma amino acids during semi-starvation in normal subjects: hypocaloric glucose vs. amino acid infusions.

Normal subjects were fed hypocaloric amounts of amino acids or glucose for 3 days to separate the effects of these nutrients from those of trauma on muscle and plasma amino acids. Intracellular and plasma levels of Val, Leu and Ile were increased in both groups but were increased to a greater extent when amino acids were infused. Intracellular free glutamine concentration in muscle tissue was not significantly altered. Some of the trauma induced changes in amino acids can be replicated by maintaining normal subjects on hypocaloric amino acids; the decrease in glutamine concentration seen with trauma is not a function of hypocaloric nutrition.

Resting energy expenditure in injured, septic, and malnourished adult patients on intravenous diets.

Energy expenditures of 237 adult patients and 37 normal subjects receiving all nutrition intravenously were analysed retrospectively. Patients were classified as nutritionally depleted (67), post-operative (96), injured (43), or septic/depleted (31). Groups were further divided into those receiving either: (1) only 5% dextrose (D5W); (2) hypocaloric regimens including glucose and amino-acids; and (3) eucaloric or hypercaloric total parenteral nutrition (TPN) which also included fat. Resting energy expenditures (REE) of normal subjects on D5W were only 85% of predicted basal values based on either the Aub-Du Bois or Harris-Benedict equations. During D5W infusions, increases for the patient groups, above these values for normal subjects, varied depending on whether they were based on absolute values or ratios to predicted values. They were: (1) 1-11% for depleted; 1-21% for post-operative; 28-30% for injured; and 18-30% for septic/depleted patients. The average increase in REE with TPN was 10%. Variability within the patient groups was high, reducing the utility of these values as a basis for estimating energy requirements of patients needing artificial nutrition. Coefficients of variation averaged 15% across patient groups when the data were expressed in kJ/kg, and were reduced only slightly, to 12%, when data were expressed as ratios to predicted values. Thus, 1 3 of the patients would differ by more than 12% from mean values, and 1 out of 20 by more than 24%. Properly performed measurements of individual energy expenditure are therefore superior to values predicted from equations or average values previously obtained from patient groups and should be used wherever possible, particularly in the very sick.