John W. Geiger

Metabolic Response to Injury and Illness: Estimation of Energy and Protein Needs from Indirect Calorimetry and Nitrogen Balance

The metabolic response to injury and illness as manifested by increases in energy expenditure and nitrogen losses makes it difficult for the clinician to evaluate calorie and protein needs. A method for determining daily calorie needs in hospitalized patients is presented. Average increases in resting metabolic expenditure for a group of patients following elective operation, skeletal trauma, skeletal trauma with head injury, blunt trauma, sepsis and burns were determined by indirect calorimetry and protein need by urinary nitrogen losses over extended time periods. Total daily calorie needs were then calculated, using the Harris-Benedict equation and adjusting this value upward using a previously measured activity and injury factor to arrive at the daily needs. Protein requirements may be determined on periodic 24 hour urine samples analyzed for the urinary urea nitrogen and adjusting this to a total nitrogen or protein equivalent. This approach to estimating the calorie nitrogen needs of the hospitalized patient under various degrees of stress more closely approximates the patients variable needs at the height of the catabolic response and during convalescence.

Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans☆

The urinary excretion of 3-methylhistidine (3MEH) in humans and animals has been used as a biologic marker for skeletal muscle protein breakdown. In rats, it has been recently suggested that there is a significant contribution of 3MEH in urine from the gastrointestinal tract due to the rapid turnover of protein in that tissue. To evaluate this point in humans, six patients with short bowel were evaluated. They were placed on three-day meat-free diets while 24-hour urine collections were obtained. The mean +/- SEM 3MEH in the short-bowel group was 3.27 +/- 0.34 mumol/kg/d and the mean +/- SEM molar ratio of 3MEH to creatinine was 0.0212 +/- 0.0012. These data were not significantly different from the control group at 95% confidence level. The results suggest that the contribution of the small intestine appears to be negligible, therefore urinary 3MEH should continue to be a valid index of skeletal muscle breakdown in man.

A comparison of the effects of skeletal trauma and surgery on the ketosis of starvation in man.

The increase of plasma ketone bodies (acetoacetic acid and beta-hydroxybutyric acid) is related to the efficient protein-sparing adaptation during a total fast by healthy man. This study investigated the response to a total fast during the postinjury state. Twenty patients with skeletal or soft-tissue trauma received 3 days of carbohydrate-free intake and then 3 more days of carbohydrate intake. Control subjects were ten postoperative patients and two healthy volunteers who received similar nutritional treatment. The trauma patients lost nearly 20 gm of nitrogen/day, which was twice control, and had a resting energy expenditure of 27.07 kcal/kg, 21.4% greater than controls. Trauma was found related to an elevation in plasma glucose and to inhibit the rise in plasma ketone bodies and free fatty acids. In contrast, indirect calorimetry showed that fat contributed 63% of the nonprotein energy on the third day of fasting and injury. These data indicate that fat is utilized by the trauma patient but that fatty metabolism is abnormal compared to starvation in healthy or mildly stressed patients.

Glutamine Supplementation of Enteral Nutrition: Impact on Whole Body Protein Kinetics and Glucose Metabolism in Critically Ill Patients

BACKGROUND Glutamine-supplemented parenteral nutrition has been reported to attenuate the early postoperative reduction in intracellular glutamine and improve protein synthesis and nitrogen balance. We investigated the effect of an enteral formula or protein and glucose kinetics and nitrogen balance in trauma patients. METHODS The enteral formula (AlitraQ) provided a mean intake of 0.35 g of glutamine/kg body weight per day to 16 trauma patients and was compared with an isonitrogenous formula that provided a mean of 0.05 g of glutamine/kg body weight per day in 14 trauma patients. After 3 days of feeding, protein kinetics were measured using a 4-hour prime-continuous infusion of L-[1-13C]leucine. Glucose kinetics were measured during the same time interval using prime-continuous infusion of [U-14C]- and [6-3H]glucose. RESULTS Nitrogen balance was not significantly different in the two groups. There were no significant differences in protein turnover, synthesis, and breakdown between the two groups. There were no significant differences in glucose turnover, oxidation, recycling, and percent of VCO2 from glucose oxidation between the two groups. CONCLUSIONS Glutamine-enriched enteral formulas are well tolerated by the severely injured patient but provide no additional nutritional advantage compared with standard enteral formulas during the first 3 days of feeding immediately after trauma.

Impact of enteral feeding of a glutamine-supplemented formula on the hypoaminoacidemic response in trauma patients

Plasma amino acid concentrations were measured during fasting and after 3 days of enteral feeding in 16 trauma patients on a glutamine-supplemented diet and 14 patients on an isonitrogenous control diet. During fasting, total amino acids, including glutamine, were depressed by 50% and this was attributed to a reduction in both essential and nonessential amino acids. The essential amino acid concentrations increased in both groups after feeding. The nonessential amino acid concentrations also increased in the control group but not in the glutamine group during feeding. Repletion of the glutamine extracellular pool was not evident after an average intake of 27.1 g per day of glutamine for 3 days. Nitrogen balance was similar for the two groups during feeding. We conclude that in this study, enteral glutamine did not increase the glutamine plasma concentration. In addition, both formulas improved the hypoaminoacidemia of essential amino acids but only the control diet improved the nonessential amino acids plasma concentration.

A physiologic basis for the provision of fuel mixtures in normal and stressed patients.

It has been suggested that lipid is a preferred fuel in stressed patients. We evaluated glucose oxidation in 20 patients (sepsis, cancer of the colon, multiple trauma, controls) while they received TPN (5.65 mg glucose/kg/min). Respiratory quotient (RQ) was measured by indirect calorimetry and the percent VCO2 arising from the oxidation of glucose was measured using [U-14C] glucose. Since RQs were 1.0 or greater in all patients, the nonprotein energy utilized by them was calculated to be derived completely from glucose. However, the kinetic data showed that glucose contributed only 55-60% of the VCO2. Protein oxidation contributed less than 20% of the VCO2, as calculated from urinary nitrogen. The difference must have been derived from fatty acid oxidation. The glucose turnover that was not oxidized was presumed to be converted to lipid at an RQ of 8.6. The net oxygen consumption and carbon dioxide production from this overall distribution resulted in an RQ of about 1.0 with only 60% coming from glucose oxidation. Since all patients responded in the same manner, it appears that the proper ratio of glucose and lipid was dictated on a physiologic basis and not on the type of disease.

Comparison of Three Methods for the Estimation of Total Nitrogen Losses in Hospitalized Patients

Since the measurement of total nitrogen output (TNO) is not routinely determined in the clinical setting, its level is frequently estimated using formulas based on the urinary urea nitrogen excretion (UUN). We measured TNO in 124 surgical patients over 990 days (TNO, 19.22 +/- 8.72 g N/day; total urinary nitrogen (TUN) 18.17 +/- 8.70 g N/day; UUN, 15.17 +/- 7.70 g N/day; mean gastrointestinal nitrogen (MGIN) 0.68 +/- 0.49 g N/day; integumental nitrogen (ITGN), 0.34 +/- 0.08 g N/day) and compared the results with the daily estimations using three different formulas: formula A, UUN + 4; formula B, UUN x 1.20 + 1.05, where 1.20 is the reciprocal of the mean ratio UUN/TUN and 1.05 the mean extraurinary nitrogen losses; and formula C, UUN x 1.0986 + 2.55, derived from the regression analysis of UUN vs TNO. TNO estimated by these formulas were 19.17 +/- 7.70, 19.26 +/- 9.24, and 19.22 +/- 8.70 g N/day, respectively. The regression analyses of the estimated TNO from the three formulas versus the measured TNO indicated that formulas A, B and C were equally accurate in estimating TNO over the entire range of UUN. However, when only values of UUN greater than or equal to 30 g N were considered, a modified formula A (UUN + 6) was the best predictor of TNO. Daily audits of the differences between the estimated and measured TNO showed comparable results for the three formulas. In 28.4 to 31.1% of the observed days the differences were higher than +/- 2 g N/day, an error which is not acceptable when estimating the protein requirements in many clinical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

LIQUID SCINTILLATION COUNTING OF THE POTASSIUM GLUCONATE DERIVATIVE OF BLOOD GLUCOSE.

Abstract The conditions for the radioactive assay of the water-soluble potassium gluconate derivative of blood glucose by liquid scintillation have been described. This method is of value when the counting of individual carbon atoms of the glucose molecule is not desired. The decline of blood glucose specific activity has been determined in a normal subject.

Protein and energy balance following femoral neck fracture in geriatric patients

To elucidate the effect of total peripheral parenteral nutrition (TPPN) on protein kinetics following injury, we compared the whole-body leucine kinetic response using a primed-constant infusion of L-[1-14C]leucine in 33 elderly patients (aged 82 +/- 1.0 years) following hip fracture and 33 healthy elderly control subjects (aged 75 +/- 0.7 years). Following a 36-hour fast, leucine release from protein breakdown was 1.2 +/- 0.10 mumol.kg-1.min-1 and leucine incorporation into protein was 0.94 +/- 0.095 mumol.kg-1.min-1 in control subjects, and in injured subjects leucine release from protein breakdown was 1.3 +/- 0.14 mumol.kg-1.min-1 and leucine incorporation into protein was 0.97 +/- 0.092 mumol.kg-1.min-1. Control and injured subjects were then administered TPPN (protein, 1.5 g amino acids.kg-1; carbohydrate, 10.0 kcal.kg-1; lipid, 15.0 kcal.kg-1) for 24 hours, and leucine kinetics were redetermined. Compared with protein kinetics in the fasting state, leucine release from protein decreased to 1.0 +/- 0.14 mumol.kg-1.min-1 and leucine incorporation into protein increased to 1.16 +/- 0.097 mumol.kg-1.min-1 in control subjects. Injured patients also responded to TPPN with a decrease in leucine release from protein breakdown (1.12 +/- 0.156 mumol.kg-1.min-1) and an increase in leucine incorporation into protein (1.29 +/- 0.164 mumol.kg-1.min-1). These results indicate that in a geriatric population, whole-body leucine kinetics following hip fracture and the anabolic response to TPPN are not significantly altered from those of uninjured subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Gluconeogenic response during glucose infusions in patients following skeletal trauma or during sepsis.

In order to quantitate the effect of sepsis and skeletal trauma on gluconeogenesis, four septic and five skeletal trauma patients were evaluated for their ability to convert 14C-L-alanine to 14C-glucose while receiving 5% dextrose by peripheral vein. In the septic group, the mean glucose pool size increased by 35% and the glucose turnover rate increased by 85% over normal. The alanine conversion averaged 11.1% of the dose. The skeletal trauma group showed a glucose pool size increase of 61%, a 100% increase in glucose turnover rate and a 11.7% conversion of the alanine dose to glucose. The increased conversion of 14C-alanine to 14C-glucose in both sepsis and skeletal trauma in the face of an exogenous glucose infusion indicates an abnormal unsuppressible response. Each of the above parameters when compared to normal values was found to be significant at levels greater than 97.5%. The percentages of the dose expired as 14CO2 in three hours were not significantly different from the normals.