Body Composition and Nutritional Support

Symposium on Surgical Nutrition

Body Composition and Nutritional Support Harry M. Shizgal, M.D.*

The first report of total parenteral nutrition in human patients was published by Elman and Weiner in 1939. 4 A solution containing amino acidand dextrose was infused intravenously in a group of surgical patients. The amino acids were obtained through the acid hydrolysis of casein, to which tryptophan and cystine were added. Despite the widespread availability of amino acids for intravenous use and the ability to infuse hypertonic dextrose into a central vein, 9 total parenteral nutrition (TPN) was not accepted as a practical method of nutritional support until 1967, primarily because its efficacy had not been demonstrated. Prior to this time it was generally accepted that lasting anabolism and a gain of cellular mass were not possible with parenteral nutrition alone. In 1967 Dudrick et al. 2 reported normal growth and development of beagle puppies that received all of their nutrition by the parenteral route. Subsequently, numerous reports have been published demonstrating the clinical benefits of TPN. The effect of TPN on the mortality associated with enteric-cutaneous fistulae is an excellent example of the importance of nutritional support. Prior to the advent of TPN, this · complication was associated with a 20 to 54 per cent mortality. 3 • 12 When TPN was added to the treatment of these patients, the mortality was reduced to 8 to 14 per cent. 7 • 13 Nutritional support prevented these patients from dying of starvation during the time required for closure of the fistula. It probably also increased the rate at which healing occurred. Morbidity and mortality are a function of multiple etiologic factors, many of which are independent of the nutritional state. As a result, the measurement of morbidity and mortality is associated with a wide variance and can only be used to demonstrate a great difference. Morbidity and mortality data, therefore, successfully demonstrated the importance of TPN in the treatment of patients with enteric-cutaneous fistulae, in whom nutritional support was compared with prolonged starvation. To detect a small difference with these measurements, such as the variation in efficacy of different TPN solutions, would require an extremely large sample.

"Professor of Surgery, McGill University; Surgeon, Royal Victoria Hospital, Montreal, Quebec, Canada

Surgical Clinics of North America- Vol. 61, No.3, June 1981

729

730

HARRY

M. SHIZGAL

Measurements of nitrogen balance provide a more accurate assessment of nutritional support, as they are a measure of the net effect of protein anabolism and catabolism. However, measurements of nitrogen balance are associated with a large experimental error. Nitrogen intake tends to be overestimated and output underestimated. As a result, a component of this error is systematic and not random and therefore cumulative. The sources of the experimental error associated with the measurement of nitrogen balance have been summarized by Vinnars. 17 An additional problem with measurements of nitrogen balance is that only a change in the nutritional state is measured. Positive nitrogen balance is indicative of net protein anabolism. However, this can occur only in the presence of malnutrition. In the normally nourished individual, nitrogen balance remains zero, regardless of the amount of protein and calories administered. The excessive administration of calories and/or protein to the normal individual results simply in an increase in body fat. A positive nitrogen balance will occur in the normally nourished individual only in response to an exercise program designed to increase muscle mass. To interpret nitrogen balance data, a knowledge of the individual's preexisting nutritional state is essential. The measurement of nitrogen balance does not yield this information. The measurement of body composition provides a quantitative assessment of both an individual's nutritional state and the effect of nutritional support. For the past several years, measurements of body composition have been employed in our laboratory to quantitatively assess both the nutritional state and the efficacy of nutritional therapy in a variety of patients.

NORMAL BODY COMPOSITION Body weight is made up of the two major components, body fat and lean body mass. The lean body mass is equivalent to the fat-free inass and consists of the extracellular mass and the body cell mass. The lean body mass is therefore anatomically and metabolically heterogenous in contrast to the body cell mass (Fig. 1). Moore et al. 10 defined the body cell mass as "that component of body composition containing the oxygen exchanging, potassium rich, glucose oxidizing, work performing tissue." The body cell mass is the metabolically active component of the body and as such is the ideal BODY COMPOSITION (Kg)

Fat

Extracellular Lean Body Mass Body Cell Mass

Figure l. Body composition in 25 normally nourished volunteers is shown. Body weight is made up of body fat and lean body mass (LBM). The LBM is, in turn, composed of the extracellular and the body cell mass.

BODY COMPOSITION

731

reference value for the body's metabolic activity as assessed by oxygen consumption, carbon dioxide production, caloric requirement, and work performance. The body cell mass is the sum of all the cellular elements of the body. It includes the cells of both smooth and skeletal muscle, the viscera, nerve tissue, and the cellular components of those tissues with a sparse cellular population (cartilage, tendon, and adipose tissue). Skeletal muscle represents approximately 60 per cent of the body cell mass, and the viscera account for 20 to 30 per cent. The remainder is made up by red cells and the cellular mass of adipose tissue, connective tissue, and the skeleton. The extracellular mass is that component of the lean body mass that surrounds the cellular mass. It is not metabolically active, does not consume oxygen, and does not perform work. Rather, it is largely concerned with transport and support. The fluid component of the extracellular mass consists of plasma and interstitial and transcellular water. Transcellular water is extracellular water that is secreted into a well-defined space, such as the lumen of the gastrointestinal tract and the cerebral, spinal, and joint spaces. The solid component of the extracellular mass includes collagen, tendon, fascia, and the skeleton.

MEASUREMENT OF BODY COMPOSITION Body composition is determined in our laboratory by multiple isotope dilution, which involves the simultaneous intravenous injection of 10 microcuries (f-tC) of human serum albumin labeled with iodine 125 (RISA), 50 ~-tC of autologous red cells tagged with chromium 51, 8 ~-tC of sodium 22, and 500 ~-tC of tritiated water. The total radiation dose to the patient receiving these isotopes is 237 millirems. This is considerably less than the 1000 to 2000 millirems resulting from many routine diagnostic radiologic procedures, such as mammography, barium meal, barium enema, intravenous pyelogram, and so forth. It is also much less than the yearly maximum permissible dose of 5000 millirems, which has been established for occupational exposure. Venous blood samples are obtained before and following isotope injection at 10-minute intervals between 60 and 110 minutes and at 4 and 24 hours. External isotope loss during this time is measured by collecting all urinary and extra-renal losses. Standard differential counting techniques are employed to determine the concentration of each isotope in plasma, whole blood, and urine and any extra-renal loss that might be present. Both deep well crystal and liquid scintillation detectors are employed. The red cell mass is calculated from the equilibrated concentration of 51 Cr-tagged red cells in whole blood. The logarithm of the plasma RISA concentration between 60 and 110 minutes is plotted against time, the independent variable. The line obtained by least square fitting is reversely extrapolated to the time of injection. The resulting intercept is employed to calculate plasma volume. The extracellular water volume is determined in an identical manner using the 22 Na-labeled plasma concentration between 60 and 110 minutes. Total body water is calculated from the equilibrated concentration of tritium-labeled water at 4 and 24 hours. The intracellular water volume is calculated as the difference between total body water (TBW) and extracellular water volume. The total exchangeable sodium (Na.) is

732

HARRY

M. SHIZGAL

determined from the plasma specific activity of2 2 Na at 24 hours. Appropriate corrections are made for both plasma water concentration and the Donnan equilibrium. The total exchangeable potassium (Ke) is determined from the following formula: Ke

=

TBW x R - Nae

where R is the ratio of sodium and potassium content divided by the water content of a whole blood sample. 14 The lean body mass is calculated by assuming that the fat-free component of body composition is 73 per cent water. Thus, lean body mass = TBW/0.73. The difference between body weight and the lean body mass is equal to body fat. The body cell mass in kilograms is calculated by multiplying Ke, in milliequivalents, by the constant 0.00833. T.he extracellular mass in kilograms is calculated as the difference between the lean body mass and the body cell mass, that is, ECM = LBM - BCM. The components of body composition vary directly with body size. To compare the body composition of different individuals, the data must be corrected for body size. This is best accomplished by expressing the components ofbody composition as a function of total body water. Total body water is employed rather than body weight, as the former is linearly related to the lean body mass, whereas body weight is a function of both the lean body mass and body fat. Thus, KJTBW and intracellular water (ICW)/TBW are both a measure of the body cell mass corrected for body size. Similarly, NaJTBW and extracellular water (ECW)/TBW are measures of the extracellular mass corrected for body size. When the data are expressed in this manner the differences between males and females disappear.

STARVATION AND INJURY During periods of partial or total starvation endogenous fuels are utilized to meet the daily energy requirements. Protein and lipid are the primary body fuels, as the available glycogen stores are meager and depleted within the initial 24 hours of total starvation. During the initial days of total starvation, the normally nourished unstressed reference man weighing 70 kg breaks down approximately 160 gm of adipose tissue and 75 gm of protein, primarily from skeletal muscle. 1 This protein is converted to glucose, which is required by those tissues, principally the central nervous system, which rely on glucose as their primary fuel. This gluconeogenesis from body protein results in a daily nitrogen loss of 12 gm, which represents a 300 gm per day loss of body cell mass. The normal unstressed individual adapts to starvation with an increased reliance on lipid and a consequent decrease in gluconeogenesis from protein. As a result, the daily urinary nitrogen loss decreases from 12 gm early in starvation to 5 gm by the fourth week of starvation. Four weeks of total starvation in a healthy, normally nourished man weighing 70 kg therefore result in a loss of body cell mass of 5. 7 kg, which represents 38 per cent of the skeletal muscle mass, or 23 per cent of the body cell mass. It has been estimated that a loss of 50 to 60 per cent of body cell mass is incompatible with survival.

733

BODY COMPOSITION

The traumatized patient, in contrast to the unstressed starved individual, is unable to increase the relative utilization of endogenous lipids, with a subsequent reduction in gluconeogenesis from protein. Furthermore, there is an increase in the resting metabolic rate, which is proportional to the severity of trauma. The resting metabolic expenditure increases by 10 per cent following uncomplicated elective operations, 10 to 25 per cent with multiple fractures, 20 to 50 per cent with major sepsis such as peritonitis, and 50 to 125 per cent with a major thermal burn. 8 There is a similar increase in the daily nitrogen loss, which ranges from 10 to 15 gm per day, following an uncomplicated operation of moderate severity. When injury is complicated with sepsis, the daily nitrogen loss increases to 15 to 25 gm per day. With severe injury and sepsis (thermal burns), it may rise to 35 gm per day. These large nitrogen losses represent an extensive erosion of the body cell mass. A nitrogen loss of 10 gm per day for one month is equivalent to a loss of body cell mass of 7 kg. The body cell mass of a normally nourished man weighing 70 kg is 25 kg, of which 15 kg is skeletal muscle. A loss of7 kg, therefore, represents 47 per cent of the skeletal muscle mass, or 28 per cent of the body cell mass. A negative nitrogen balance of 30 gm pe.r day for one week represents a loss of body cell mass of 5.3 kg. At this rate, by 2V2 weeks, in excess of 50 per cent of the body cell mass is lost. Thus, starvation and injury, especially when complicated with sepsis, result in a rapid erosion of the cellular mass. The effect of moderate injury and starvation was demonstrated by measurements of body composition performed before and following an elective operation of moderate severity in 19 normally nourished patients. 16 The majority of patients underwent either a gastrectomy or a colon resection. Body composition was determined preoperatively and on the fifth postoperative day. Body composition prior to surgery was normal. By the fifth postoperative day these patients had developed mild malnutrition. They lost 1.8 ± 0.9 kg of body fat and 3.2 ± 0.6 kg of their body cell mass, a 13.9 per cent reduction (Table 1). The resected speciman accounted for a portion of this loss. The decrease in the body cell mass was accompanied by a concomitant 2.4 ± 0.5 kg expansion of the extracellular mass. As a result, the 3.9 per cent loss of body weight was not a good reflection of the 13.9 per cent decrease in the cellular mass. Similar measurements were perform~d in 75 clinically diagnosed malnourished patients. 16 The majority had developed postoperative complications, and all had been referred for a course ofTPN. Their body composition

Table 1. Body Composition Following a Major Elective Operation DIFFERENCE PRE-OPERATIVE

Body weight (kg) Body fat (kg) ECM (kg)f BCM (kg)t

66.2 18.2 24.9 23.1

± ± ± ±

1.9 1.6 0.9 1.5

*p < 0.05 by paired Studt•nt' s t test. tECM =extracellular mass; BCM =body cell mass.

POST -OPERATIVE

63.5 16.4 27.3 19.9

± 1.8* ± 1.5* ± 0.9* ± 1.4*

KG(%)

-2.7 (-4) -1.8(-10) 2.4 (10) -3.2 (-14)

734

HARRY

M.

SHIZGAL

Table 2. Body Composition in Severe Malnutrition

Number Body weight (kg) Body fat (kg) ECM (kg)f BCM (kg){

NORMAL

MALNOURISHED

DIFFERENCE

VOLUNTEERS

PATIENTS

KG(%)

25 70.4 20.2 25.6 24.7

± 2.5 ± 1.4 ± 0.9 ± 1.1

75 58.9 12.7 31.8 14.7

± ± ± ±

1.8* 1.2* 0.9* 0.6*

-17.5 -7.5 6 -10

(-16) (-37) (24) (-40)

*p < 0.05 by unpaired Student's t test. t ECM = extracellular mass; BCM = body cell mass.

was characterized by a contracted body cell mass and an expansion of the extracellular mass. Because of the increase in the extracellular mass, the change in body weight did not accurately reflect the change in the nutritional state (Table 2). The Na.:K. ratio was significantly elevated in both the postoperative (Na.:Ke = 1.29 ± 0.11) and the malnourished patients (Na.:Ke = 1.95 ± 0.08). This ratio is a measure of the extracellular mass, expressed as a function of the body cell mass. In the normally nourished individual, the body cell mass and the extracellular mass are approximately equal in size and therefore the Na.:K.ratio approximates unity (Na.:K. = 0.98 ± 0.02). With malnutrition, this ratio increases because of the reciprocal changes in the body cell mass and the extracellular mass. The Na.:Ke ratio is therefore a sensitive index of the nutritional state. In 25 normally nourished volunteers, the upper 95 per cent confidence limit was 1.22. Malnutrition has therefore been defined as a ratio of Na. to K. of more than 1.22. The validity of this definition of malnutrition has been established by measurements of body composition performed during the past several years in more than 1700 patients. 6

PROTEIN AND CALORIC REQUIREMENTS Although the importance of nutritional support is well established, especially for the patient subjected to a prolonged catabolic stress, the protein and caloric requirements of the critically ill patient remain controversial. 5 • 11 Studies were therefore carried out to determine (1) the caloric requirements of patients receiving TPN, (2) the optimum amino acid concentration of TPN solutions, and (3) the relative efficacy of carbohydrate and lipid as the major caloric source. The results obtained are probably applicable to all hospitalized patients regardless of the route used for nutritional support. This study involved 204 patients who received TPN for 4447 days. We performed 533 body composition studies to evaluate 308 periods of TPN of approximately two weeks' duration. The patients were randomly allocated to receive one of the following three TPN solutions: (1) 2.5 per cent crystalline L-amino acids (Travasol, Travenol-Baxter Laboratories, Canada) with 25 per cent dextrose, (2) 5 per cent crystalline L-amino acids (Travasol) with 25 per cent dextrose, and (3) a 10 per cent lipid emulsion (Intralipid, Pharmacia, Canada) infused with an equal volume of a solution containing 5 per cent

BODY COMPOSITION

735

amino acids (Travasol) and 25 per cent dextrose. Since the lipid emulsion and the hypertonic dextrose solution were infused at the same rate via a Y tube, the final solution administered contained 2.5 per cent amino acids, 12.5 per cent dextrose, and 5 per cent lipid. There were 102, 68, and 34 patients who received the first, second and third TPN solutions, respectively. The number of patients in each group was unequal since the study was performed in two stages. Initially all patients referred for TPN were randomized to receive either the first or second solution. In the second stage of the study, patients were randomized between the first and third solutions. Each patient in the first two groups received 100 ml of 10 per cent Intralipid weekly to prevent the development of essential fatty acid deficiency. To quantitatively assess the efficacy ofTPN, body composition measurements were performed at the beginning and at two-week intervals during the course ofTPN. The rate of change in the body cell mass was used to evaluate the efficacy ofTPN. In a normally nourished individual, the body cell mass is not expected to increase, regardless of the caloric and protein intake, except with a special exercise program designed specifically to increase muscle mass. Therefore, each group was subdivided according to the presence or absence of preexisting malnutrition at the onset of each TPN period. Malnutrition was defined by the presence of a ratio of Nae to Ke of greater than 1.22. In the normally nourished patients, the body cell mass, as expected, did not increase with any of the three solutions. Body weight increased slightly, principally because of an increase in body fat. Otherwise their body composition remained unchanged. In the patients with preexisting malnutrition, TPN with each of the three solutions produced a significant improvement in body composition (Table 3). Two weeks of TPN with 2.5 per cent amino acids and 25 per cent dextrose resulted in a mean increase in body weight of 1.1±0.5 kg (p<0.5), due principally to an increase in body cell mass of 0.9±0.3 kg (p<0.01). Similar changes occurred in the malnourished patients receiving the 5 per cent amino acid solution and in those who received lipids. Increasing the amino acid concentration from 2.5 to 5 per cent and infusing 47 per cent of the nonprotein calories .as lipid did not appear to affect the efficiency of TPN. The. latter group, however, received 15 per cent more calories than did the other two groups. Multiple linear regression was therefore performed to account for the different caloric, protein, and lipid intake. The daily change in the body cell mass (ABCM per day) was correlated with the carbohydrate, lipid, and protein calories per kilogram of body weight infused and with the Nae:Ke ratio, a measure of the nutritional state. This analysis was performed on a total of 212 TPN periods by combining the data obtained in the three groups of malnourished patients. This approach is possible since the ratio of amino acid to nonprotein calories and the ratio of lipid to carbohydrate calories were different in the three solutions. The following statistically significant (p<0.01) multiple linear regression was obtained: ~

BCM/day = -348.5 + 4.9 CHO + 3.2 lipid + 4.7 protein + 98.7 Nae:Ke

There was considerable scatter of points about the regression, as indicated by a correlation coefficient of0.4. The correlation coefficient was improved (r=0.6, p<0.01) by correlating the daily change in the body cell mass, as grams

'-1 ~

Q'l

Table 3. The Effect of TPN on Body Composition in Patients with Preexisting Malnutrition 2.5% AMINO ACID, 25% DEXTROSE

5% AMINO ACID, 25% DEXTROSE

2.5% AMINO ACID, 12.5% DEXTROSE, 5% LIPID

NORMAL

Pre

VOLUNTEERS

Weight (kg) Body fat (kg) Lean body mass (kg) Body cell mass (kg) Extracellular mass (kg)

70.4 20.2 50.3 24.7 25.6

K.,/TBW (mEq/L) Na,/TBW (mEq/L) Na,/K.,

80.0 ± 1.0 77.5 ± 0.9 0.98 ± 0.02

Patients Studies TPN periods TPN days Total calories (cal/kg/day) Carbohydrate (cal!kg/day) Lipid (cal!kg/day) Protein (gm/kg/day)

± 2.5 ± ± ± ±

1.4 1.9 1.1

0.9

25

57.5 11.9 45.6 15.5 30.1

± ± ± ± ±

Post

1.5 0.9 1.1

0.5 0.8

56.1 ± 1.1 t 94.6 ± l.Ot 1.79 ± 0.07t

58.6 12.4 46.2 16.4 29.9

± ± ± ± ±

1.4* 0.8 1.0 0.4* 0.9

59.2 ± 1.3*t 91.5 ± 1.2*t 1.66 ± 0.06*t

55 151 90 14.9 ± 0.3t 49.5 ± 1.4 43.6 ± 1.2 0.8 ± 0.1 1.26 ± 0.04

Pre 56.9 13.6 43.3 14.9 28.4

± ± ± ± ±

Post

1.5 0.9 1.3 0.5 0.9

57.7 14.4 43.3 16.1 27.3

56.5 ± 1.1 t 92.2 ± l.ll t 1.71 ± 0.06t

13.8 53.6 41.6 2.5 2.37

± ± ± ± ±

1.4* 1.0 1.0 0.5* 0.7

61.1 ± 1.2*t 88.0 ± 1.2*t 1.50 ± 0.05*t 50 125 72 ± 0.2 ± 1.6 ± 1.2 ± 0.5t ± 0.07t

*Significantly different (p < 0.05) from pre-mean by a paired Student's t test. t Significantly different (p < 0.05) from normal volunteers by an analysis of variance and Scheffe' s test. t Significantly different (p < 0.05) from the other two groups by an analysis of variance and Scheffe' s test.

Pre 57.4. 13.6 43.8 14.6 29.2

± ± ± ± ±

Post

2.3 1.6 1.5 0.7

59.1 15.5 43.6 15.6 28.0

1.1

± ± ± ± ±

2.4* 1.6* 1.5 0.8* 1.0

58.2 ± 1.6*t 91.3 ± 1.3t 1.70 ± O.ll t

54.7 ± 1.4t 94.1 ± 1.3t 1.85 ± O.ll t 29 81 50 14.0 57.1 27.4 24.4 1.36

± 0.22

± 2.3t ± 1.1 t ±

1.2t

± 0.06

::r:

~

~ 'JJ

:I:

N

~

737

BODY COMPOSITION

per kilogram of body cell mass per day, with the carbohydrate, lipid, and protein intake, expressed as calories per kilogram of body cell mass. The statistical significance of the regression coefficients also improved. N evertheless, in the subsequent discussion, the caloric intake is expressed as a function of body weight. Although it is less precise, the results obtained are more applicable to daily clinical practice. The regression indicates that the rate at which a depleted body cell mass is restored is related to caloric intake and the degree of malnutrition and is not affected by increasing the amino acid concentration from 2.5 to 5 per cent. The regression coefficient associated with carbohydrate intake was larger than the one associated with lipid intake. This indicates that in the malnourished patient, carbohydrate calories are more efficient than lipid calories. This difference is demonstrated in Figure 2, in which, using the regression equation mentioned earlier, the daily change in the body cell mass, in kilograms per day, is related to the nonprotein calories infused. Because the regression involves four independent variables and one dependent variable, a multidimensional space is required to plot the experimental data and the regression. A two-dimensional graph was plotted by setting several of the independent variables constant. Thus, in Figure 2, the Na.:Ke ratio is set at 1.50 (indicative of moderate malnutrition), and the daily amino acid infusion rate is set at 1.26 gm per kilogram of body weight, the mean amino acid infusion rate in the patients who received the 2.5 per cent amino acid solution. As illustrated in Figure 2, the body cell mass is maintained with a daily infusion of 36 cal per kilogram of body weight when all of the nonprotein calories are carbohydrate, and 55 cal per kilogram of body weight with lipid. When 50 per cent of the nonprotein calories are carbohydrate, an infusion of 44 cal per kilogram of body weight will maintain the body cell mass. A daily infusion of 50 nonprotein calories per kilogram of body weight will result in a daily body cell mass increase of 69 gm per day with the carbohydrate solution and 16 gm per day when 50 per cent of the nonprotein calories are lipid. These data therefore demonstrate that in depleted malnourished patients carbohydrate calories were far more efficient than lipid calories. An additional important consideration is the difference in cost 120-

>

"'

"0

100-

......

80-

"'

>

60-

u

40-


20-

50%CHO Vso%Lipid

NaeiKe=1.5 AA =1.26g/Kg

~

"0

...... ::! al

0 50

60

70

cai/Kg BW/day Figure 2. The relationship between the· daily change in body cell mass and the nonprotein caloric intake is depicted. The amino acid intake is maintained constant at 1.26 gm/kg of body weight and the Nae:Kee ratio is set at 1.5, indicating moderate malnutrition. The nonprotein calories were either carbohydrate, lipid or 50 per cent carbohydrate and 50 per cent lipid.

738

HARRY M. SIDZGAL

120 100

>

80

>

60

~ :::E

40

"C "' ...... E?

"'

u

al


Nae /Ke =1.50

20 0 10

20

30

cai/Kg

40 BW/day

50

60

Figure 3. The relationship between the daily change in body cell mass and the nonprotein caloric intake when the daily amino acid infusion rate is 1.26 and 2.37 gm/kg of body weight (solid lines) is shown . The latter are the mean rates at which the amino acids were infused in patients receiving the 2.5 per cent and 5 per cent amino acid solutions, respectively. The Na.,:K.ratio is maintained constant at 1.5. All of the nonprotein calories are carbohydrate. The broken line represents an amino acid intake of 2.37 gm/kg when taking into account the extra calories associated with the higher amino acid intake.

between intravenous carbohydrate and lipid. In our institution, an intravenous lipid calorie is 1180 per cent more expensive than a carbohydrate calorie. The regression data also demonstrated that doubling the amino acid concentration did not alter the repletion rate of a depleted body cell mass. In Figure 3 the daily change in the body cell mass is plotted against the caloric intake, with a daily amino acid intake of either 1.26 or 2.37 gm per kilogram of body weight. These amino acid infusion rates represent the mean amino acid intake of the malnourished patients receiving the 2.5 and 5 per cent solutions, respectively. The Na.:K. ratio is set at 1.50, and all of the nonprotein calories are carbohydrate. Increasing the amino acid concentration shifted the curve to the left. Therefore at the same caloric intake, there is a more rapid restoration of the body cell mass. However, this apparently increased efficiency disappeared when the extra calories associated with the increased amino acid concentration were accounted for. Wilmore, in a recent review, 18 pointed out that at any level of protein intake, nitrogen balance improves as the caloric intake is increased. With a constant caloric intake, nitrogen balance improves as the protein intake is increased. However, the latter relationship reaches a maximum so that a further increase in protein intake does not result in any further improvement in nitrogen balance. In the present study the flat portion of the curve was probably achieved with the 2.5 per cent solution. As a result, increasing the amino acid concentration above 2.5 per cent had very little effect on the rate at which a depleted body cell mass was restored. These data have had a significant impact on the cost of TPN in our institution. When this study was carried out, the amino acid concentrations of the commercially available TPN solutions varied from 2.5 to 4.25 per cent, representing a considerable variation in cost. With the 2.5 per cent solution, amino acids accounted for 81 per cent of the solution's costs. Increasing the amino acid concentration to 5 per cent resulted in an 84 per cent cost increase. Thus, considerable cost savings were achieved by employing a 2.5 per cent amino acid solution and using glucose as the major source of nonprotein calories. Intralipid is used only to prevent the development of essential fatty acid deficiency and is therefore infused at a rate of 500 ml twice a week. The regression equation also demonstrated a relationship between the restoration rate of a depleted body cell mass and the degree of malnutrition. This is illustrated in Figure 4, in which the daily change in the body cell mass

739

BonY CoMPOSITION

120 AA=1.26g/Kg

>

100

"' ~

80

"'

>

60

::!: u

40

~ "0

...... Ill


20

10

20

30

40

50

60

70

cai/Kg BW/day Figure 4. The relationship between caloric intake and the daily change in body cell mass with varying degrees of malnutrition as assessed by Na,:K.,. The Na,:K, ratio increases as the severity of malnutrition increases. Thus, an Na,:K, ratio of 1.5 indicates mild malnutrition, whereas an Na,:K, ratio of 2.5 is indicative of severe malnutrition.

is plotted against the caloric intake for increasingly more severe malnutrition, as indicated by the Nae:Ke ratio. In Figure 4 the daily amino acid intake is set to equal 1.26 gm per kilogram of body weight, the mean intake of the malnourished patients who received the 2.5 per cent solution. As the severity of malnutrition increased, the caloric requirements for maintenance decreased. Thus, with moderate malnutrition (Nae:Ke = 1.5) the body cell mass is maintained with a caloric intake of 36 cal per kilogram of body weight. With severe malnutrition (Nae:Ke = 2.5), 16 cal per kg is sufficient for maintenance. With caloric intakes in excess of the amount required for maintenance, the restoration of the depleted body cell mass is more rapid in the more malnourished. Thus, with a daily infusion of 50 cal per kilogram of body weight, the body cell mass increases at a rate of 69 gm per day when the Nae:Ke ratio is 1.5 and 168 gm per day when the Nae:Ke·ratio is 2.5. Thus, as the malnourished state is corrected, the restoration rate of the depleted body cell mass decreases continuously and becomes zero as the normally nourished state is achieved. This is consistent with our observation that in the normally nourished individual, TPN has no effect on the body cell mass. These data also emphasize the importance of a knowledge of an individual's nutritional state when evaluating the results of nutritional therapy. This is true both with body composition measurements and nitrogen balance data. In the normally nourished individual, nitrogen balance will never exceed zero despite the caloric and protein intake, except with a special exercise program designed to increase muscle mass. Thus, in evaluating the effects of nutritional support it is imperative to differentiate the normally nourished from the malnourished individual. Otherwise, the data from the normally nourished group will bias the malnourished data. It is also important to estimate the degree of malnutrition present, as this will affect the response to nutritional therapy. The data described indicate that the restoration rate of a depleted body cell mass is related to caloric intake and the degree of malnutrition but is not affected by increasing the amino acid intake from 1.3 gm per kg per day to 2.4 gm per kg per day. Elwyn et al. have reported a similar relationship between the restoration of the body cell mass and caloric intake. 5 In a group of depleted

740

HARRY

M.

SHIZGAL

patients receiving TPN, they described a straight line relationship between nitrogen balance and the daily caloric intake. Their equation had an intercept of -24.3 mg nitrogen per kilogram of body weight and a slope of 1.4 mg nitrogen per calorie. Using the mean values for the malnourished patients receiving the 2.5 per cent solution, this equation predicted a mean daily positive nitrogen balance of 45 mg per kilogram of body weight. This is equivalent to a daily increase in the body cell mass of 64 gm per day. Using the same data, our regression equation predicted a restoration rate of 69 gm per day. At this rate, two weeks ofTPN would result in an increase in the body cell mass of 0.97 kg, which is the increase measured in the malnourished patients who received the 2.5 per cent solution for a mean of 14.7 days (see Table 3). Although the data described were obtained in patients receiving TPN, the conclusions are probably applicable to all forms of nutritional support. Thus, the restoration rate of a malnolirished individual is directly dependent on the caloric intake, provided that the protein intake is adequate. There are no apparent advantages to increasing the daily protein intake to levels above 1.5 to 2 gm per kilogram of body weight. Carbohydrate calories are more efficient than lipid calories in restoring the malnourished individual. These data also emphasize that correction of the malnourished state is relatively slow compared with the rate at which it develops. The normally nourished individual during the first few days of starvation breaks down more than 300 gm per day of body cell mass. A much more rapid breakdown occurs with trauma, especially when complicated with sepsis. However, in spite of large caloric intakes the body cell mass is restored at a rate of only 50 to 100 gm per day.

REFERENCES 1. Cahill, G. F., Jr.: Starvation in man. N. Engl. J. Med., 282:668, 1970. 2. Dudrick, S. J., Wilmore, D. W., and Vars, H. M.: Long-term total parenteral nutrition with growth in puppies and positive nitrogen balance in patients. Surg. Forum, 18:356, 1967. 3. Edmunds, L. D., Jr., Williams, E. M., and Welch, C. E.: External fistula arising from the gastrointestinal tract. Ann. Surg., 152:445, 1960. 4. Elman, R., and Weiner, D. 0.: Intravenous alimentation with special reference to protein (amino acid) metabolism. J.A.M.A., 112:796, 1939. 5. Elwyn, D. H., Gump, F. E., Munro, H. M., et a!.: Changes in nitrogen balance of depleted patients with increasing infusions of glucose. Am. J. Clin. Nutr., 32:1597, 1979. 6. Forse, R. A., and Shizgal, H. M.: The Na,/K, ratio: A predictor of malnutrition. Surg. Forum, 31 :89-92; 1980. 7. Himal, H. S., Allard, J. R., Nadeau, J. E., eta!: The importance of adequate nutrition in closure of small intestinal fistulae. Br. J. Surg., 61:724, 1974. 8. Kinney, J. M.: Energy requirements of the surgical patient. In Ballinger, W. F. (ed.): Manual of Surgical Nutrition. American College of Surgeons. Philadelphia, W. B. Saunders Co., 1975, pp. 223-235. 9. Moore, F. D.: Metabolic Care of the Surgical Patient. Philadelphia, W. B. Saunders Co., 1959. . 10. Moore, F. D., Olesen, K. H., McMurrey, J. D., eta!.: The Body Cell Mass and Its Supporting Environment. Philadelphia, W. B. Saunders Co., 1963. 11. Peters, C. P., and Fischer, J. E.: Studies in calorie to nitrogen ratio for total parenteral nutrition. Surg. Gynecol. Obstet., 151:1-8, 1980. 12. Roback, S. A., and Nicoloff, D. M.: High output entero-cutaneous fistula of the small bowel. Am. J. Surg., 123:317, 1972. 13. Sheldon, E. F., Gardiner, B. M., Way, L. W., eta!.: Management of gastrointestinal fistulas. Surg. Gynecol. Obstet., 133:385, 1971.

BODY COMPOSITION

741

14. Shizgal, H. M., Spanier, A. H., Humes, J., eta!.: Indirect measurement of total exrhangeable potassium. Am. J. Physiol., 233:F253-F259, 1977. 15. Shizgal, H. M., and Forse, R. A.: Protein and calorie requirements with total parenteral nutrition. Ann. Surg., 192:132, 1980. 16. Shizgal, H. M.: The effect of malnutrition on body composition. Surg. Gynecol. Obstet., 152:22, 1981. 17. Vinnars, E.: Effect of intravenous amino acid administration on nitrogen retention. Scand. J. Clin. Lab. Invest., 27(Suppl. 1): 117, 1971. 18. Wilmore, D. W.: Energy requirements for maximum nitrogen retention. In Green, H. L., Holliday, M. A., and Munro, H. M. (eds.): Clinical Nutrition Update: Amino Acids. Chicago, American Medical Association, 1977. Department of Surgery Royal Victoria Hospital 687 Pine Avenue West Montreal, Quebec Canada