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Total Parenteral Nutrition in the Critically III Patient
----.III. -.:--
--===-
ICCP _neil on crRicl1 clre Total Parenteral Nutrition In the Critically III Patlent* Michel Lemoyne, M.D.; and Khursheed N. ]eejeebhoy, M.B., B.S., Ph.D.
Nutritional support in the critically ill patient represents a special challenge for the nutritional support team, because of the complex interaction of injury-sepsis and nutrient utilization. In addition, sick patients are more likely to develop complications during intravenous feeding. ThIs article offers principles and guidelines for the proper assessment and nutritional support of the critically ill patient. METABOLIC EFFECTS OF STARVATION, INJURY AND SEPSIS
The human body is not a static entity, but is in a constant state of flux. TIssues are synthesized and broken dowri continuously, processes which need energy. In the critically ill patient there is a variety of factors which prevent the individual from meeting his! her energy requirements. These include: (a) anorexia and inability to eat; (b) possible associated gastrointestinal disease; (c) increased or altered requirements; and (d) altered utilization. The imbalance *From the
of Medicine, Division QfGastroentetology,
De~ent
Toronto General Hospital and University of Toronto, Toronto, Canada. Reprint requeats: Dr.leejeebhoy, University of.Toronto, Room 6352 Medical Science Buililing, Toronto, Ontario, Canada M5S lAB
FAT STORES
FFA ------
MASS STORES
AA----'!i~
(MUSCLE)
ketogenesis - - - -
glucose
gluconeogenesis
(AA
urea
588
Starvation results in reduced insulin levels which promote the mobilization of adipose tissue fat as free fatty acids (FFA). The enhanced output of FFA provides the fuel required for peripherai tissues, particularly muscle. Part of the increased FFA output is oxidized by the liver to ketones. In addition, there is enhanced hepatic glucose output because of glycogenolysis and gluconeogenesis. Despite the increased output of FFA in early fasting, there is continued catabolism of muscle protein, which supplies all amino acids including alanine and glutamine. These amino acids are deaminated in the liver and kidneys, and the carbon skeletons of the deaminated ketoacids are converted to glucose while the nitrogen moiety is
NONPREFERRED GLUCOSE USERS
glycogen
LEAN BODY
Staroation (Fig 1)
__
LIVER '----~
between reduced intake and augmented or altered requirements results in effects which are similar to those of starvation. In addition, altered utilization imposes additional derangements which may result in loss of body tissue and altered function. lienee, in order to give nutritional support to such patients, it is necessary to understand the metabolic effects of both starvationl and acute injury and sepsis. 2.3
a!!lmonia
PREFERRED GLUCOSE USERS (ERAIN - RBC)
FIGURE
1. Metabolism during starvation.
Parenteral Nutrition In Critically II (Lemoyne, Jee}eebho'/)
excreted as urea and ammonia. Hence, muscle breakdown provides substrate for gluconeogenesis, which supplies the brain with glucose, its main fuel, at a time of deprivation. This is associated with a negative nitrogen balance of 10-12 glday, which is maximal after four days of complete fasting, but then begins to taper offand becomes as low as 3 g1dayas starvation extends beyond one week. Chronically starved man is dependent for survival on conserving body protein while providing a continuing fuel supply for vital organs. These opposing needs are met by reducing the overall energy needs of the body, as demonstrated by a decrease in energy expenditure of up to 35 percent during starvation, and reducing the need for gluconeogenesis as ketoacids begin to substitute for glucose as a brain fuel, therefore conserving amino acid precursors from muscle tissue. In summary, from the biochemical point of vie~ one of the important adaptive changes of starvation is the increase in the absolute and relative amounts of fat consumed for energy purposes. This is accomplished by increasing the pool of FFA so that even muscle, a tissue that normally utilizes FFA as a major fuel source in the fasted state increases its utilization of FFA to the point where 90 percent of its calories may be derived from their oxidation. MoreoveI; the increment in lipolysis provides the liver with fatty acids which are converted to ketone bodies and released into the circulation. This minimizes protein breakdown by switching from glucose to ketone bodies as the main source of energy.
Injury and Sepsis (Fig 2) Fifty years ago, Cuthbertson4 showed that trauma caused a rise in the outputs of urea, phosphorus,
NEUROEr.:DOCRINE
ACTIVATION ----:>~
potassium and nitrogen indicative of cell catabolism. The source ofnitrogen and other intracellular constituents that are lost following injury has never been completely defined. However, the nitrogen-sulphur and nitrogen-potassium ratios of the urinary losses suggest that the nitrogen loss is mainly from muscle. 5 These catabolic changes reach a maximum four to eight days after an injuryS and their magnitude is proportional to the level of protein intake before the injury (poor nutritional intake is known to reduce the degree and length ofthe protein catabolic response to injury). 6 Nitrogen balance techniques give infurmation about net exchange of nitrogen, but isotopic tracer studies examine the dynamics of nitrogen within the body. Studies by Long et aF in acutely ill septic surgical patients have indicated that a negative nitrogen balance can be the result ofan increased protein synthesis rate with an even greater increase in protein breakdown. More recently it has been shown that in trauma, counter-regulatory hormones that oppose the action of insulin, namely glucagon, glucocorticoids and catecholamines, are commonly elevated in association with injury and sepsis, and that the combination of these three hormones accelerates nitrogen loss. In addition, Clowes et al3 have shown that there is a circulating factor in the plasma of septic subjects which increases muscle proteolysis in vitro. Hence, there is a variety of factors acting in concert to accelerate the output of nitrogen from the body during trauma and sepsis, although the exact mechanisms which dominate this process are as yet uncertain. The injured septic subject often shows mild-to-moderate hyperglycemia, and even when it is scarcely noticeable, there will be an abnormal response to a glucose tolerance test. That glucose intolerance might be due to inability of the
I
FAT
I~--------->~
FFA
to---~-
GLUCOSE
LIVER
NON-BCAA MUSCLE -----~~
?CIRCULATING FACTORCS) ~
FIGURE
2. Metabolism during injury and sepsis.
PROTEIN ( Aft.)
UREA
A~~HONIA
CHEST I 89 I 4 I APRIL. 1988
589
injured patient to oxidize glucose was disproved by Long et al. 8 In fact, they showed that injured patients oxidize glucose at a normal or even increased rate in the presence of stable circulation. Gump and colleagues, 9 using a technique ofregional catheterization, demonstrated an increased hepatic production of glucose despite the presence of hyperglycemia. One has to remember that gluconeogenesis receives much of its substrate, alanine, from muscle proteolysis. Isotopic glucose studies have shown that the hepatic output ofglucose is not only increased following injury, but cannot be inhibited by the usual infusion of exogenous glucose. Finally, in a study of surgical patients not receiving TPN, indirect calorimetry has indicated that 75-90 percent of the caloric expenditure is from body fat, while protein provides the remaindel: 10 From the above discussion on metabolic effects, it is clear that starvation plus added trauma and/or sepsis have the effect of mobilizing energy stores from adipose tissue, but in addition, there is gradual and continual breakdown of muscle protein with release of amino acid nitrogen, resulting in a loss of muscle mass and thus of vital tissue. Although muscle loss is minimized in starvation, this is not the case in trauma or sepsis where the process may be accelerated. What has not been clearly elucidated, howeveJ; is the signal that elicits this response. NUTRITIONAL ASSESSMENT OF THE CRmCALLY ILL PATIENT
Changes in Body Weight Clinically, the injured-septic patient is seen to waste despite receiving what appears to be an adequate caloric intake. How does this happen? In the past, hypermetabolism was evoked to explain this phenomenon and so it was claimed that the metabolic rate in such patients was excessive. It followed, therefore, that the only way of preventing weight loss was to give massive amounts of calories. As has been discussed previously, however, during injury and sepsis, breakdown of muscle occurs and releases utilizable energy substrates. Muscle is 80 percent water and 20 percent solid mattel: Assuming that most of the solid is protein and carbohydrate, the catabolism of 1 kg of muscle releases 800 kcal ofenergy substrates. In contrast, 1 kg of fat releases 7,000 kcal. ll Thus, when the individual derives energy from muscle catabolism rather than fat, there will be substantial weight loss. This loss occurs because weight for weight, muscle has only one ninth the calories of fat. For example, if the metabolic requirements ofan individual were 2,000 kca1lday, and these were to be met from muscle alone, he or she would have to catabolize 2.5 kg of muscle per day. In contrast, the same needs could be met by catabolizing 570
only 0.3 kg offat per day. Thus, muscle catabolism may cause dramatic wasting without a need to invoke hypermetabolism.
Importance of Loss of Body Components Body composition can be measured noninvasively through measurements of total body nitrogen by prompt gamma emission (PGE),12 total body potassium by whole body counting, 12 and body fat by anthropometry. A combination of these measurements estimates lean body mass. As we have shown previously, the fall in TBK and TBN paralleled the clinical appearance of the patient13 and subsequently predicted the occurrence of a nutrition-associated complication, namely: sepis. At this stage the reHective question arises as to whether malnutrition causes its ill effects solely through loss of body tissue, or whether there are functional effects which may precede the loss of body tissue and which may be restored by nutritional support prior to a full restoration of normal body composition. If the adverse effects of malnutrition are due solely to altered body composition, then surely the best way to decide whether a person needs support is to measure body composition and give support to those with reduced body constituents. This rationale indeed has been the basis of currently practiced nutritional assessment techniques such as anthropometry (weight, arm circumference, skinfold thickness) and creatinine-height index. This reasoning led as well to measurements of TBK and TBN in institutions with facilities for measuring these components. Also based on this philosophy, nutritional support was assessed by its effect on these same measurements.
Functional Effects of Malnutrition Synthesis of hepatic secretory proteins: It has been established that total hepatic protein and RNA levels decline during fasting. Hence, in conditions of deficient input it might be expected that the plasma concentration of albumin and other plasma proteins secreted by the liver (transferrin and retinol-binding protein) would decline. Howevet; the major circulating protein, albumin, has a long half-life (20 days) and therefore its plasma level does not indicate early altered synthesis. Furthermore, plasma protein levels depend upon several factors other than nutrient deprivation, such as liver disease, altered liver function associated with septicemia, and excessive protein losses (protein-losing enteropathy, nephropathy). In conclusion, malnutrition cannot be adequately assessed by measuring plasma protein levels in critically sick patients. Immunodeficiency: Malnutrition is the most common cause of secondary immunode6ciency, and as a consequence, infection is one of the most frequent Parenteral Nutrition in CritIcally III (Lemoyne, Jeejeebhoy)
Table I-Factors Affecting or Suppressing DeR Infections (viral, bacterial, mycoses) Metabolic and systemic disorders (uremia, IBD, sarcoidosis) Malignancy Chemotherapy and radiotherapy Drugs (steroids, immunosuppressants) General anesthesia Surgery Zinc deficiency
complications of malnutrition. All facets of host resistance are altered, but cell-mediated immune response is generally affected earlier and more severely. However, the complement system and opsonic function of plasma may be altered too. A recent report points to the effect of £ibronectin, a high molecular weight glycoprotein, in helping the function of macrophage cells. 14 The levels of fibronectin are sensitive to disturbed nutrition. 15 Finally, malnutrition also alters levels of serum immunoglobulins. The most common form ofin vivo testing ofimmune competence in hospitalized patients is the measurement of delayed cutaneous hypersensitivity (DCH) to known antigens; however, it is well known that a number of factors other than malnutrition can alter or suppress DCH (Table 1). Hence, those factors must be taken into account before attributing abnormalities of skin testing to malnutrition alone. 16 Skeletal muscle function: It has been shown that a course of nutritional support 17.18 can decrease postoperative morbidity and mortality. However, these improvements were not associated with any significant change in the different indices used to predict the presence of malnutrition. Thus, the good outcome did not correlate with the changes in body composition, suggesting that the reversal of the adverse effects of malnutrition was not based on improvement in the traditional parameters of nutrition, such as gain in body nitrogen or an increase in plasma proteins. Rather, there is recent evidence that functional abnormalities may not be the result of simple loss of lean tissue, as might easily be thought, and furthermore may recover before the restoration of lean tissue with nutritional support. When pondering the matter of what function might be more closely related to malnutrition than the two above-mentioned, one is led to consider that of skeletal muscle. Muscle wasting is prominent in severe malnutrition. Recent examination of this parameter has indeed shown it to be more sensitive to nutrient deprivation and restoration than any other objective method yet developed. 19-22 The method chosen for these studies involves stimulation of the ulnar nerve at the wrist in order to test the function of the adductor pollicis of the right hand, according to the method of Edwards. 23 He demonstrated that any given muscle is representative of all skeletal muscles, including the very vital diaphragm. 24
Parameters of muscle contraction measured were the force-frequency curve (ie, the force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50, 100 Hz), the relaxation rate (MRR) and fatiguability. Muscle function in the nonnal individual. Age and sex do not have any effect on the F10/F50 or MRR, although the maximum force of contraction (F50) is higher in men than in women and tends to decrease with age. 19
Muscle function in the malnourished patient. If the dietary intake is ~ 90 percent of EBEE, the parameters ofmuscle function remain normal. However, ifit is < 90 percent of EBEE for at least one week, the F10/F50 increases and MRR decreases and there is a linear relation between the dietary intake and the parameters of muscle function. 19 In a study of obese patients administered a hypocaloric diet (400 kcallday) for four weeks and then starved for another four weeks, Russell et alil demonstrated that the parameters of muscle function, normal at the beginning, became abnormal during the hypocaloric diet and remained abnormal during fasting (F10/F50 increased, MRR decreased, muscle fatigued). Most interesting was the fact that those abnormalities were present at a time when there were no significant changes in body composition (serum albumin and transferrin, creatinine-height index, anthropometry, TBK and TBN).21 Of greater interest was a study of anorexia nervosa patients which showed that these abnormalities were reversible with refeeding at a time when indices of body composition were still abnormal. 22 Other authors have demonstrated that respiratory muscle strength is decreased in malnourished patients25-27 and that this loss of strength is related to a reduction in body cell mass. 25 The majority of patients have shown improvement in muscle strength when treated with TPN for two weeks. . Muscle function in the critically ill patient. Acute sepsis and/or trauma may affect parameters of muscle function. Recently19 it has been shown that in a traumatized patient the F10/FSO is normal, whereas the MRR is decreased temporarily for up to two days. The reason for this phenomenon is presently unknown. In the septic patient, the F10/FSO is slightly increased although not as much as in the malnourished state but MRR remains normal. Howevet; if both conditions (trauma or sepsis) are superimposed on malnutrition, the specific modifications associated with the latter condition oceUI: Finally, it is important to stress that treatment with steroids (up to 30 mg/day for up to 30 days), surgery and renal failure without malnutrition,28 are without effect on the different muscle function parameters. Muscle function abnonnalities: What is the rnechaCHEST I 89 I 4 I APRIL. 1988
571
nism? As for the mechanism of this altered function, a clue for further study comes from an analysis of ra~ and human30 muscle biopsies. In all studies, there was a significant rise in intracellular calcium while none of the other ions was altered. This finding suggests that muscle function may be altered because of factors altering the energy status of the muscle, inhibiting calcium efBux across the sarcolemma, thus altering the contraction-relaxation characteristics of the muscle. Another possibility is that type II fiber atrophy, seen with malnutrition, may reduce the relaxation rate because the remaining type I fibers have a slower relaxation rate. Howeve~ studies by Whittaker et al31 have shown that identical abnormalities of muscle function could be seen in muscles mainly composed of type I fibers. As one may judge from the above discussion, further studies are necessary to define the specific biochemicalJmorphologic changes which cause abnormal muscle function in malnutrition. MACRONUTRIENT REQUIREMENTS
Protein Requirements Protein utilization has been estimated by observing the amount of protein and energy needed to create a positive nitrogen balance. However; M unro6 has drawn attention to the fact that the nitrogen excretion in urine in starvation is dependent on the preceding nitrogen intake. In another study, Greenberg et al31 noticed that the quantity of nitrogen given was an important determinant of nitrogen balance, and providing that 2 glkg of amino acids per day were administered to their patients, a positive nitrogen balance was seen even when total calories were less than the metabolic requirements. Collins et al33 showed that although the total body nitrogen (TBN) was as well maintained with amino acid infusions as with amino acids plus glucose, the patients who received amino acids plus energy recovered earlier and had fewer complications. The point is made once again that our aim in giving nutritional support should be the improvement in function, rather than a positive nitrogen balance or a rise in TBN. Studies by Anderson et al34 have shown that the nitrogen requirements for balance in stable there was inadults are only 0.4 glkglday. Howeve~ creased nitrogen retention with increasing intake and this gain was linear over a range of 0.25 to 2 glkglday. Administration of substantial amounts must be tempered by the fact that altered renal and/or hepatic function will reduce tolerance to amino acid loads. Considering these factors, it seems desirable on average to prescribe 1.0-1.5 glkg ideal body weight (IBW)/ day of a balanced amino acid mixture.
Energy Requirements Energy requirements are dependent on a number of 572
factors which include the body surface area (derived from height and weight), age and sex. It can be predicted with reasonable accuracy by the HarrisBenedict equation. 35 Men: kcals/24h=66.473+13.756xwt (kg) +5.0033 x ht (cm) - 6.7550 x age (yr). Women: kcals/24h = 655.0955 + 9.5634 wt (kg) +l.8498xht (cm)-4.6756xage (yr). These equations calculate the expected basal energy expenditure (EBEE). In a study done by Shike36 in 20 adults of various heights and weights, the calculated data agreed with the observed energy consumption calculated by indirect calorimetry with a variation of ± 10 percent. To these values (EBEE) must be added the specific dynamic activity of food (thermogenesis) to give the resting energy expenditure in the bed-ridden patient (REE). Elwyn et al37 stated that REE can be approximated from the BEE by increasing it by 10 percent. In contrast, malnutrition reduces the BEE to an extent which may be as much as 35 percent. Injury, sepsis and especially bums were believed to increase energy requirements by approximately 30, 60 and 100 percent, respectively. Howeve~ this concept of hypermetabolism has recently come into question and three studies38-40 (two of them controlled) have failed to find that injured-septic patients are markedly hypermetabolic. The mean increase in the metabolic rate of injured-septic patients studied by Askanazi et al39 exceeded the expected value by only 14 percent and of those studied by Roulet et al38 by only 12.9 percent. In any case, it should be recognized that an increase in metabolic rate of even 60 percent, when referred to BEE (about 25 kcallkglday) works out to be a requirement of only 40 kcallkglday or 2,800 kcal in a 70 kg individual. Hence, there is little evidence ofa need for 4,000-6,000 kcal, as was sometimes recommended in the past.
Sources of Energy: Glucose vs Fat Based on the known protein-sparing effects of glucose and the observed increased metabolic rate in such patients, parenteral nutrition using very large amounts of glucose was advocated for treating injuredseptic individuals. However, in recent years the importance of glucose as the only source of non-protein calories has been questioned. MacFie et a141 and Jeejeebhoy et ala showed that patients with gastrointestinal disease utilize glucose and fat equally well, and even more recently Baker et al40 demonstrated that critically ill patients were maintaining protein balance while receiving fuel mixtures just as well as when they received glucose as the only source of non-protein calories. Furthermore, by using a glucose-fat mixture, we can prevent the complications associated with the administration of substantial amounts of glucose.
These include hepatic steatosis,43 respiratory failure, 44 and essential fatty acid deficiency as well as the commonly encountered problems when rates of administration are drastically reduced (accidentally or otherwise) in the presence of high circulating levels of insulin (in response to the glucose). Recommendations for Energy Intake
Earlier studies have demonstrated that increasing the caloric intake above 40 kcalJkg IBW did not enhance nitrogen balance. Furthermore, this figure corresponds to the theoretic maximum calculated on the basis ofa 60 percent increase in the metabolic rate referred to earlier. This caloric intake will also comfortably exceed the energy requirements noted for injured-septic patients. 38-40 ELECTROLITES
General Principles
The importance offluid and electrolyte replacement fur promoting tissue perfusion and ionic equilibrium is self-eVident. The processes ofmalnutrition and refeeding are both associated with major changes in electrolyte balance. With malnutrition there is loss of the intracellular ions potassium, magnesium and phosphorus, together with a gain in sodium and water. Hence, to accommodate the reverse (intracellular gain) on refeeding it is necessary to supply "extra" potassium, magnesium and phosphorus while expecting a "de rigueur" positive balance in sodium and water retention, particularly during refeeding with carbohydrate..n This process is referred to as "refeeding edema" and improves concomitantly with nutritional status. In emaciated patients, particularly elderly subjects and those with cardiopulmonary disease, refeeding has to be undertaken very carefully because of the risk of pulmonary edema occurring. Electrolyte Recommendations
The recommendations fur electrolytes are listed in Table 2. MICRONUTRIENTS
The micronutrients belong to two main groups of substances: vitamins and trace elements. Both are essential because they regulate metabolic processes in many different ways, either as coenzymes or as essential elemental constituents of enzyme complexes regulating the utilization of carbohydrates, proteins and fats. Trace Elements
Seven trace elements have been shown to be necessary fur health in human beings. They are: iron, zinc, coppel; chromium, selenium, iodine and cobalt. Most
Table 2-Electrolyte Recommendationa Average Patient Sodium
100-120 mmollday
Potassium Magnesium Phosphorus
80-120 mmollday 12-15 mmollday 14-16 mmollday
Calcium
6.8-10 mmollday
f With GI losses - 50-60 mmollday in elderly and/or cardiopulmonary disease ~ With renal failure f With GI losses f When glucose alone is given ~ With renal failure
of these elements, except chromium, are excreted through the gastrointestinal tract, raising the possibility that abnormal gastrointestinal losses may raise requirements in patients with disease of the gastrointestinal tract. On the other hand, renal disease does not reduce the need for these elements. Trace element recommendations: The recommendations for the principal trace elements in total parente~ nutrition solutions are listed in Table 3. 45 Vitamins
Vitamins are essential nutrients which are active in Table 3-Trace Element Becommendationa in Total Parenteral Nutrition Solutions Iron
Zinc
Copper Chromium Selenium Iodine Manganese*
Men: 1 mglday Women: Premenopausal: 2 mglday Postmenopausal: 1 mglday 1 mglday 2.5 mglday when infusing amino acids + 12 mglL of small intestinal 8uid loss + 17 mgIL of stool loss 0.3 mglday 0.5 mglday with diarrhea None with abnonnalliver function 10-20 ..,glday 120 ..,glday 120 ..,g1day 0.2-0.8 mglday None with abnonnalliver function
*No deficiency during TPN administration has been described in humans.
Table 4-Vatamin B e c _ for Patienta Receiving Total ParentertJl Nutrition Vitamin A Vitamin D Vitamin E Vitamin K Thiamine Ribo8avin Niacin Pantothenic acid Pyridoxine Folic acid Vitamin Bll Vitamin C Biotin
2500 IU/day 400 IU/day 50 IU/day (a-Tocopherol)41 10 mglweek 5 mglday 5 mglday 50 mglday 15 mglday 5 mglday 5 mglday 12..,glday 300-500 mglday 60 ..,glday CHEST I 89 I 4 I APRIL. 1988
573
minute quantities. While it is obvious that these substances have to be given in any regimen of total parenteral nutrition to avoid deficiency, the optimum dose and frequency of administration has not been studied in detail in patients receiving total parenteral nutrition. . Vitamin recommendations: The recommendations for patients receiving total parenteral nutrition are listed in Table 4. 46 ACKNOWLEDGMENTS: The authors thank the Medical Research Council ofCanada for the Fellowship award to Michel Lem~e and for financial support of the work described (MA. #7923), and Janet Chrupala for her expert typing. REFERENCES 1 Cahill GF: Starvation in man. N Engl J Med 1970; 282:668-75 2 Kinney JM, Elwyn DU. Protein metabolism and injury. Ann Rev Nutr 1983; 3:433-66 3 Clowes GHA, George BC, Villee CA, Saravis CA. Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. N Eng} J Med 1983; 308:545-52 4 Cuthbertson D~ Observations on disturbance of metabolism produced by injury to limbs. Quart J Med 1932; 25:233-46 5 Cuthbertson DE The metabolic response to injury and its nutritional implications: retrospect and prospect. JPEN 1979; 3:108-29 6 Munro HN. General aspects ofthe regulation of protein metabolism by diet and hormones. In: Mammalian protein metabolism (vol 1), Munro HN, Allison JB, eds. New York: Academic Press, 1964; 381-481 7 Long CL, Jeevanandam B, Kim BM, Kinney JM. Whole body protein synthesis and catabolism in septic man. Am J Clio Nutr 1977; 30:1340 8 Long CL, Spencer JL, Kinney JM, Geiger JW: Carbohydrate metabolism in man: effect ofelective operations and major injury. J Appl Physiol1971; 31:110-16 9 Gump FE, Long CL, Killian ~ Kinney JM. Studies of glucose intolerance in septic injured patients. J Uauma 1974; 14:378-88 10 Duke JU, Jorgensen SB, Bmell JR, Long CL, Kinney JM. Contribution of protein to calorie expenditure following injury. Surgery 1970; 68:168-74 11 Uegsted OM. Energy requirements. In: Present knowledge in nutrition. Washington, D.C.: The Nutrition Foundation, 1984; 1-6 12 McNeill KG, Mernagh JR, Jeejeebhoy leN, Wolman SL, Harrison JR. In vivo measurements of body protein based on the determination of nitrogen by prompt gamma analysis. Am J Clin Nutr 1979; 32:1955-61 13 McNeill KG, Mernagh JR, Harrison JE, Stewart S, Jeejeebhoy KN. Changes in body protein, body potassium and lean body mass during total parenteral nutrition. JPEN 1982; 6:106-08 14 Saba TM, Dillon BC, Lanser ME. Fibronectin and phagocytic host defense: relationship to nutritional support. JPEN 1983; 7:62-8 15 Howard L, Dillon BC, Saba TM, Hofmann S, Cho E. Decreased plasma fibronectin during starvation in man. JPEN 1984; 8:237-44 16 lWomey ~ Ziegler D, Rombeau J. Utility of skin testing in nutritional assessment: a critical review. JPEN 1982; 6:50-8 17 Mullen IL, Buzby G~ Matthews DC, Smale BF, Rosato EF: Reduction of operative morbidity and mortality by combined preoperative and post-operative nutritional support. Ann Surg 1980; 192:604-13 18 Rombeau J, Bamt LR, Williamson CE, Mullen JL. Preoperative
574
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44 Askanazi J, Elwyn DH, Silverberg BS, Rosenbaum SH, Kinney JM. Respiratory distress syndrome secondary to a high carbohydrate load: a case report. Surgery 1980; 87:596-98 45 Russell DMcR, Tsallas G, Pipa DA. 'Irace elements in parenteral nutrition. In: Biological aspects of metals and metal-related diseases, Sarkar B, ed. New York: Raven Press, 1983; 121-32 46 Nichoalds GE, Meng HC, Caldwell MD. Vitamin requirements in patients receiving total parenteral nutrition. Arch Surg 1977;
112:1061-64
47 Thurlow PM, Grant J~ Vitamin E and total parenteral nutrition. In: Vitamin E, biochemical, hematological and clinical aspects. Ann NY Acad Sci 1982; 393:121-32
CHEST I 89 I 4 I APRIL, 1988
575
--===-
ICCP _neil on crRicl1 clre Total Parenteral Nutrition In the Critically III Patlent* Michel Lemoyne, M.D.; and Khursheed N. ]eejeebhoy, M.B., B.S., Ph.D.
Nutritional support in the critically ill patient represents a special challenge for the nutritional support team, because of the complex interaction of injury-sepsis and nutrient utilization. In addition, sick patients are more likely to develop complications during intravenous feeding. ThIs article offers principles and guidelines for the proper assessment and nutritional support of the critically ill patient. METABOLIC EFFECTS OF STARVATION, INJURY AND SEPSIS
The human body is not a static entity, but is in a constant state of flux. TIssues are synthesized and broken dowri continuously, processes which need energy. In the critically ill patient there is a variety of factors which prevent the individual from meeting his! her energy requirements. These include: (a) anorexia and inability to eat; (b) possible associated gastrointestinal disease; (c) increased or altered requirements; and (d) altered utilization. The imbalance *From the
of Medicine, Division QfGastroentetology,
De~ent
Toronto General Hospital and University of Toronto, Toronto, Canada. Reprint requeats: Dr.leejeebhoy, University of.Toronto, Room 6352 Medical Science Buililing, Toronto, Ontario, Canada M5S lAB
FAT STORES
FFA ------
MASS STORES
AA----'!i~
(MUSCLE)
ketogenesis - - - -
glucose
gluconeogenesis
(AA
urea
588
Starvation results in reduced insulin levels which promote the mobilization of adipose tissue fat as free fatty acids (FFA). The enhanced output of FFA provides the fuel required for peripherai tissues, particularly muscle. Part of the increased FFA output is oxidized by the liver to ketones. In addition, there is enhanced hepatic glucose output because of glycogenolysis and gluconeogenesis. Despite the increased output of FFA in early fasting, there is continued catabolism of muscle protein, which supplies all amino acids including alanine and glutamine. These amino acids are deaminated in the liver and kidneys, and the carbon skeletons of the deaminated ketoacids are converted to glucose while the nitrogen moiety is
NONPREFERRED GLUCOSE USERS
glycogen
LEAN BODY
Staroation (Fig 1)
__
LIVER '----~
between reduced intake and augmented or altered requirements results in effects which are similar to those of starvation. In addition, altered utilization imposes additional derangements which may result in loss of body tissue and altered function. lienee, in order to give nutritional support to such patients, it is necessary to understand the metabolic effects of both starvationl and acute injury and sepsis. 2.3
a!!lmonia
PREFERRED GLUCOSE USERS (ERAIN - RBC)
FIGURE
1. Metabolism during starvation.
Parenteral Nutrition In Critically II (Lemoyne, Jee}eebho'/)
excreted as urea and ammonia. Hence, muscle breakdown provides substrate for gluconeogenesis, which supplies the brain with glucose, its main fuel, at a time of deprivation. This is associated with a negative nitrogen balance of 10-12 glday, which is maximal after four days of complete fasting, but then begins to taper offand becomes as low as 3 g1dayas starvation extends beyond one week. Chronically starved man is dependent for survival on conserving body protein while providing a continuing fuel supply for vital organs. These opposing needs are met by reducing the overall energy needs of the body, as demonstrated by a decrease in energy expenditure of up to 35 percent during starvation, and reducing the need for gluconeogenesis as ketoacids begin to substitute for glucose as a brain fuel, therefore conserving amino acid precursors from muscle tissue. In summary, from the biochemical point of vie~ one of the important adaptive changes of starvation is the increase in the absolute and relative amounts of fat consumed for energy purposes. This is accomplished by increasing the pool of FFA so that even muscle, a tissue that normally utilizes FFA as a major fuel source in the fasted state increases its utilization of FFA to the point where 90 percent of its calories may be derived from their oxidation. MoreoveI; the increment in lipolysis provides the liver with fatty acids which are converted to ketone bodies and released into the circulation. This minimizes protein breakdown by switching from glucose to ketone bodies as the main source of energy.
Injury and Sepsis (Fig 2) Fifty years ago, Cuthbertson4 showed that trauma caused a rise in the outputs of urea, phosphorus,
NEUROEr.:DOCRINE
ACTIVATION ----:>~
potassium and nitrogen indicative of cell catabolism. The source ofnitrogen and other intracellular constituents that are lost following injury has never been completely defined. However, the nitrogen-sulphur and nitrogen-potassium ratios of the urinary losses suggest that the nitrogen loss is mainly from muscle. 5 These catabolic changes reach a maximum four to eight days after an injuryS and their magnitude is proportional to the level of protein intake before the injury (poor nutritional intake is known to reduce the degree and length ofthe protein catabolic response to injury). 6 Nitrogen balance techniques give infurmation about net exchange of nitrogen, but isotopic tracer studies examine the dynamics of nitrogen within the body. Studies by Long et aF in acutely ill septic surgical patients have indicated that a negative nitrogen balance can be the result ofan increased protein synthesis rate with an even greater increase in protein breakdown. More recently it has been shown that in trauma, counter-regulatory hormones that oppose the action of insulin, namely glucagon, glucocorticoids and catecholamines, are commonly elevated in association with injury and sepsis, and that the combination of these three hormones accelerates nitrogen loss. In addition, Clowes et al3 have shown that there is a circulating factor in the plasma of septic subjects which increases muscle proteolysis in vitro. Hence, there is a variety of factors acting in concert to accelerate the output of nitrogen from the body during trauma and sepsis, although the exact mechanisms which dominate this process are as yet uncertain. The injured septic subject often shows mild-to-moderate hyperglycemia, and even when it is scarcely noticeable, there will be an abnormal response to a glucose tolerance test. That glucose intolerance might be due to inability of the
I
FAT
I~--------->~
FFA
to---~-
GLUCOSE
LIVER
NON-BCAA MUSCLE -----~~
?CIRCULATING FACTORCS) ~
FIGURE
2. Metabolism during injury and sepsis.
PROTEIN ( Aft.)
UREA
A~~HONIA
CHEST I 89 I 4 I APRIL. 1988
589
injured patient to oxidize glucose was disproved by Long et al. 8 In fact, they showed that injured patients oxidize glucose at a normal or even increased rate in the presence of stable circulation. Gump and colleagues, 9 using a technique ofregional catheterization, demonstrated an increased hepatic production of glucose despite the presence of hyperglycemia. One has to remember that gluconeogenesis receives much of its substrate, alanine, from muscle proteolysis. Isotopic glucose studies have shown that the hepatic output ofglucose is not only increased following injury, but cannot be inhibited by the usual infusion of exogenous glucose. Finally, in a study of surgical patients not receiving TPN, indirect calorimetry has indicated that 75-90 percent of the caloric expenditure is from body fat, while protein provides the remaindel: 10 From the above discussion on metabolic effects, it is clear that starvation plus added trauma and/or sepsis have the effect of mobilizing energy stores from adipose tissue, but in addition, there is gradual and continual breakdown of muscle protein with release of amino acid nitrogen, resulting in a loss of muscle mass and thus of vital tissue. Although muscle loss is minimized in starvation, this is not the case in trauma or sepsis where the process may be accelerated. What has not been clearly elucidated, howeveJ; is the signal that elicits this response. NUTRITIONAL ASSESSMENT OF THE CRmCALLY ILL PATIENT
Changes in Body Weight Clinically, the injured-septic patient is seen to waste despite receiving what appears to be an adequate caloric intake. How does this happen? In the past, hypermetabolism was evoked to explain this phenomenon and so it was claimed that the metabolic rate in such patients was excessive. It followed, therefore, that the only way of preventing weight loss was to give massive amounts of calories. As has been discussed previously, however, during injury and sepsis, breakdown of muscle occurs and releases utilizable energy substrates. Muscle is 80 percent water and 20 percent solid mattel: Assuming that most of the solid is protein and carbohydrate, the catabolism of 1 kg of muscle releases 800 kcal ofenergy substrates. In contrast, 1 kg of fat releases 7,000 kcal. ll Thus, when the individual derives energy from muscle catabolism rather than fat, there will be substantial weight loss. This loss occurs because weight for weight, muscle has only one ninth the calories of fat. For example, if the metabolic requirements ofan individual were 2,000 kca1lday, and these were to be met from muscle alone, he or she would have to catabolize 2.5 kg of muscle per day. In contrast, the same needs could be met by catabolizing 570
only 0.3 kg offat per day. Thus, muscle catabolism may cause dramatic wasting without a need to invoke hypermetabolism.
Importance of Loss of Body Components Body composition can be measured noninvasively through measurements of total body nitrogen by prompt gamma emission (PGE),12 total body potassium by whole body counting, 12 and body fat by anthropometry. A combination of these measurements estimates lean body mass. As we have shown previously, the fall in TBK and TBN paralleled the clinical appearance of the patient13 and subsequently predicted the occurrence of a nutrition-associated complication, namely: sepis. At this stage the reHective question arises as to whether malnutrition causes its ill effects solely through loss of body tissue, or whether there are functional effects which may precede the loss of body tissue and which may be restored by nutritional support prior to a full restoration of normal body composition. If the adverse effects of malnutrition are due solely to altered body composition, then surely the best way to decide whether a person needs support is to measure body composition and give support to those with reduced body constituents. This rationale indeed has been the basis of currently practiced nutritional assessment techniques such as anthropometry (weight, arm circumference, skinfold thickness) and creatinine-height index. This reasoning led as well to measurements of TBK and TBN in institutions with facilities for measuring these components. Also based on this philosophy, nutritional support was assessed by its effect on these same measurements.
Functional Effects of Malnutrition Synthesis of hepatic secretory proteins: It has been established that total hepatic protein and RNA levels decline during fasting. Hence, in conditions of deficient input it might be expected that the plasma concentration of albumin and other plasma proteins secreted by the liver (transferrin and retinol-binding protein) would decline. Howevet; the major circulating protein, albumin, has a long half-life (20 days) and therefore its plasma level does not indicate early altered synthesis. Furthermore, plasma protein levels depend upon several factors other than nutrient deprivation, such as liver disease, altered liver function associated with septicemia, and excessive protein losses (protein-losing enteropathy, nephropathy). In conclusion, malnutrition cannot be adequately assessed by measuring plasma protein levels in critically sick patients. Immunodeficiency: Malnutrition is the most common cause of secondary immunode6ciency, and as a consequence, infection is one of the most frequent Parenteral Nutrition in CritIcally III (Lemoyne, Jeejeebhoy)
Table I-Factors Affecting or Suppressing DeR Infections (viral, bacterial, mycoses) Metabolic and systemic disorders (uremia, IBD, sarcoidosis) Malignancy Chemotherapy and radiotherapy Drugs (steroids, immunosuppressants) General anesthesia Surgery Zinc deficiency
complications of malnutrition. All facets of host resistance are altered, but cell-mediated immune response is generally affected earlier and more severely. However, the complement system and opsonic function of plasma may be altered too. A recent report points to the effect of £ibronectin, a high molecular weight glycoprotein, in helping the function of macrophage cells. 14 The levels of fibronectin are sensitive to disturbed nutrition. 15 Finally, malnutrition also alters levels of serum immunoglobulins. The most common form ofin vivo testing ofimmune competence in hospitalized patients is the measurement of delayed cutaneous hypersensitivity (DCH) to known antigens; however, it is well known that a number of factors other than malnutrition can alter or suppress DCH (Table 1). Hence, those factors must be taken into account before attributing abnormalities of skin testing to malnutrition alone. 16 Skeletal muscle function: It has been shown that a course of nutritional support 17.18 can decrease postoperative morbidity and mortality. However, these improvements were not associated with any significant change in the different indices used to predict the presence of malnutrition. Thus, the good outcome did not correlate with the changes in body composition, suggesting that the reversal of the adverse effects of malnutrition was not based on improvement in the traditional parameters of nutrition, such as gain in body nitrogen or an increase in plasma proteins. Rather, there is recent evidence that functional abnormalities may not be the result of simple loss of lean tissue, as might easily be thought, and furthermore may recover before the restoration of lean tissue with nutritional support. When pondering the matter of what function might be more closely related to malnutrition than the two above-mentioned, one is led to consider that of skeletal muscle. Muscle wasting is prominent in severe malnutrition. Recent examination of this parameter has indeed shown it to be more sensitive to nutrient deprivation and restoration than any other objective method yet developed. 19-22 The method chosen for these studies involves stimulation of the ulnar nerve at the wrist in order to test the function of the adductor pollicis of the right hand, according to the method of Edwards. 23 He demonstrated that any given muscle is representative of all skeletal muscles, including the very vital diaphragm. 24
Parameters of muscle contraction measured were the force-frequency curve (ie, the force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50, 100 Hz), the relaxation rate (MRR) and fatiguability. Muscle function in the nonnal individual. Age and sex do not have any effect on the F10/F50 or MRR, although the maximum force of contraction (F50) is higher in men than in women and tends to decrease with age. 19
Muscle function in the malnourished patient. If the dietary intake is ~ 90 percent of EBEE, the parameters ofmuscle function remain normal. However, ifit is < 90 percent of EBEE for at least one week, the F10/F50 increases and MRR decreases and there is a linear relation between the dietary intake and the parameters of muscle function. 19 In a study of obese patients administered a hypocaloric diet (400 kcallday) for four weeks and then starved for another four weeks, Russell et alil demonstrated that the parameters of muscle function, normal at the beginning, became abnormal during the hypocaloric diet and remained abnormal during fasting (F10/F50 increased, MRR decreased, muscle fatigued). Most interesting was the fact that those abnormalities were present at a time when there were no significant changes in body composition (serum albumin and transferrin, creatinine-height index, anthropometry, TBK and TBN).21 Of greater interest was a study of anorexia nervosa patients which showed that these abnormalities were reversible with refeeding at a time when indices of body composition were still abnormal. 22 Other authors have demonstrated that respiratory muscle strength is decreased in malnourished patients25-27 and that this loss of strength is related to a reduction in body cell mass. 25 The majority of patients have shown improvement in muscle strength when treated with TPN for two weeks. . Muscle function in the critically ill patient. Acute sepsis and/or trauma may affect parameters of muscle function. Recently19 it has been shown that in a traumatized patient the F10/FSO is normal, whereas the MRR is decreased temporarily for up to two days. The reason for this phenomenon is presently unknown. In the septic patient, the F10/FSO is slightly increased although not as much as in the malnourished state but MRR remains normal. Howevet; if both conditions (trauma or sepsis) are superimposed on malnutrition, the specific modifications associated with the latter condition oceUI: Finally, it is important to stress that treatment with steroids (up to 30 mg/day for up to 30 days), surgery and renal failure without malnutrition,28 are without effect on the different muscle function parameters. Muscle function abnonnalities: What is the rnechaCHEST I 89 I 4 I APRIL. 1988
571
nism? As for the mechanism of this altered function, a clue for further study comes from an analysis of ra~ and human30 muscle biopsies. In all studies, there was a significant rise in intracellular calcium while none of the other ions was altered. This finding suggests that muscle function may be altered because of factors altering the energy status of the muscle, inhibiting calcium efBux across the sarcolemma, thus altering the contraction-relaxation characteristics of the muscle. Another possibility is that type II fiber atrophy, seen with malnutrition, may reduce the relaxation rate because the remaining type I fibers have a slower relaxation rate. Howeve~ studies by Whittaker et al31 have shown that identical abnormalities of muscle function could be seen in muscles mainly composed of type I fibers. As one may judge from the above discussion, further studies are necessary to define the specific biochemicalJmorphologic changes which cause abnormal muscle function in malnutrition. MACRONUTRIENT REQUIREMENTS
Protein Requirements Protein utilization has been estimated by observing the amount of protein and energy needed to create a positive nitrogen balance. However; M unro6 has drawn attention to the fact that the nitrogen excretion in urine in starvation is dependent on the preceding nitrogen intake. In another study, Greenberg et al31 noticed that the quantity of nitrogen given was an important determinant of nitrogen balance, and providing that 2 glkg of amino acids per day were administered to their patients, a positive nitrogen balance was seen even when total calories were less than the metabolic requirements. Collins et al33 showed that although the total body nitrogen (TBN) was as well maintained with amino acid infusions as with amino acids plus glucose, the patients who received amino acids plus energy recovered earlier and had fewer complications. The point is made once again that our aim in giving nutritional support should be the improvement in function, rather than a positive nitrogen balance or a rise in TBN. Studies by Anderson et al34 have shown that the nitrogen requirements for balance in stable there was inadults are only 0.4 glkglday. Howeve~ creased nitrogen retention with increasing intake and this gain was linear over a range of 0.25 to 2 glkglday. Administration of substantial amounts must be tempered by the fact that altered renal and/or hepatic function will reduce tolerance to amino acid loads. Considering these factors, it seems desirable on average to prescribe 1.0-1.5 glkg ideal body weight (IBW)/ day of a balanced amino acid mixture.
Energy Requirements Energy requirements are dependent on a number of 572
factors which include the body surface area (derived from height and weight), age and sex. It can be predicted with reasonable accuracy by the HarrisBenedict equation. 35 Men: kcals/24h=66.473+13.756xwt (kg) +5.0033 x ht (cm) - 6.7550 x age (yr). Women: kcals/24h = 655.0955 + 9.5634 wt (kg) +l.8498xht (cm)-4.6756xage (yr). These equations calculate the expected basal energy expenditure (EBEE). In a study done by Shike36 in 20 adults of various heights and weights, the calculated data agreed with the observed energy consumption calculated by indirect calorimetry with a variation of ± 10 percent. To these values (EBEE) must be added the specific dynamic activity of food (thermogenesis) to give the resting energy expenditure in the bed-ridden patient (REE). Elwyn et al37 stated that REE can be approximated from the BEE by increasing it by 10 percent. In contrast, malnutrition reduces the BEE to an extent which may be as much as 35 percent. Injury, sepsis and especially bums were believed to increase energy requirements by approximately 30, 60 and 100 percent, respectively. Howeve~ this concept of hypermetabolism has recently come into question and three studies38-40 (two of them controlled) have failed to find that injured-septic patients are markedly hypermetabolic. The mean increase in the metabolic rate of injured-septic patients studied by Askanazi et al39 exceeded the expected value by only 14 percent and of those studied by Roulet et al38 by only 12.9 percent. In any case, it should be recognized that an increase in metabolic rate of even 60 percent, when referred to BEE (about 25 kcallkglday) works out to be a requirement of only 40 kcallkglday or 2,800 kcal in a 70 kg individual. Hence, there is little evidence ofa need for 4,000-6,000 kcal, as was sometimes recommended in the past.
Sources of Energy: Glucose vs Fat Based on the known protein-sparing effects of glucose and the observed increased metabolic rate in such patients, parenteral nutrition using very large amounts of glucose was advocated for treating injuredseptic individuals. However, in recent years the importance of glucose as the only source of non-protein calories has been questioned. MacFie et a141 and Jeejeebhoy et ala showed that patients with gastrointestinal disease utilize glucose and fat equally well, and even more recently Baker et al40 demonstrated that critically ill patients were maintaining protein balance while receiving fuel mixtures just as well as when they received glucose as the only source of non-protein calories. Furthermore, by using a glucose-fat mixture, we can prevent the complications associated with the administration of substantial amounts of glucose.
These include hepatic steatosis,43 respiratory failure, 44 and essential fatty acid deficiency as well as the commonly encountered problems when rates of administration are drastically reduced (accidentally or otherwise) in the presence of high circulating levels of insulin (in response to the glucose). Recommendations for Energy Intake
Earlier studies have demonstrated that increasing the caloric intake above 40 kcalJkg IBW did not enhance nitrogen balance. Furthermore, this figure corresponds to the theoretic maximum calculated on the basis ofa 60 percent increase in the metabolic rate referred to earlier. This caloric intake will also comfortably exceed the energy requirements noted for injured-septic patients. 38-40 ELECTROLITES
General Principles
The importance offluid and electrolyte replacement fur promoting tissue perfusion and ionic equilibrium is self-eVident. The processes ofmalnutrition and refeeding are both associated with major changes in electrolyte balance. With malnutrition there is loss of the intracellular ions potassium, magnesium and phosphorus, together with a gain in sodium and water. Hence, to accommodate the reverse (intracellular gain) on refeeding it is necessary to supply "extra" potassium, magnesium and phosphorus while expecting a "de rigueur" positive balance in sodium and water retention, particularly during refeeding with carbohydrate..n This process is referred to as "refeeding edema" and improves concomitantly with nutritional status. In emaciated patients, particularly elderly subjects and those with cardiopulmonary disease, refeeding has to be undertaken very carefully because of the risk of pulmonary edema occurring. Electrolyte Recommendations
The recommendations fur electrolytes are listed in Table 2. MICRONUTRIENTS
The micronutrients belong to two main groups of substances: vitamins and trace elements. Both are essential because they regulate metabolic processes in many different ways, either as coenzymes or as essential elemental constituents of enzyme complexes regulating the utilization of carbohydrates, proteins and fats. Trace Elements
Seven trace elements have been shown to be necessary fur health in human beings. They are: iron, zinc, coppel; chromium, selenium, iodine and cobalt. Most
Table 2-Electrolyte Recommendationa Average Patient Sodium
100-120 mmollday
Potassium Magnesium Phosphorus
80-120 mmollday 12-15 mmollday 14-16 mmollday
Calcium
6.8-10 mmollday
f With GI losses - 50-60 mmollday in elderly and/or cardiopulmonary disease ~ With renal failure f With GI losses f When glucose alone is given ~ With renal failure
of these elements, except chromium, are excreted through the gastrointestinal tract, raising the possibility that abnormal gastrointestinal losses may raise requirements in patients with disease of the gastrointestinal tract. On the other hand, renal disease does not reduce the need for these elements. Trace element recommendations: The recommendations for the principal trace elements in total parente~ nutrition solutions are listed in Table 3. 45 Vitamins
Vitamins are essential nutrients which are active in Table 3-Trace Element Becommendationa in Total Parenteral Nutrition Solutions Iron
Zinc
Copper Chromium Selenium Iodine Manganese*
Men: 1 mglday Women: Premenopausal: 2 mglday Postmenopausal: 1 mglday 1 mglday 2.5 mglday when infusing amino acids + 12 mglL of small intestinal 8uid loss + 17 mgIL of stool loss 0.3 mglday 0.5 mglday with diarrhea None with abnonnalliver function 10-20 ..,glday 120 ..,glday 120 ..,g1day 0.2-0.8 mglday None with abnonnalliver function
*No deficiency during TPN administration has been described in humans.
Table 4-Vatamin B e c _ for Patienta Receiving Total ParentertJl Nutrition Vitamin A Vitamin D Vitamin E Vitamin K Thiamine Ribo8avin Niacin Pantothenic acid Pyridoxine Folic acid Vitamin Bll Vitamin C Biotin
2500 IU/day 400 IU/day 50 IU/day (a-Tocopherol)41 10 mglweek 5 mglday 5 mglday 50 mglday 15 mglday 5 mglday 5 mglday 12..,glday 300-500 mglday 60 ..,glday CHEST I 89 I 4 I APRIL. 1988
573
minute quantities. While it is obvious that these substances have to be given in any regimen of total parenteral nutrition to avoid deficiency, the optimum dose and frequency of administration has not been studied in detail in patients receiving total parenteral nutrition. . Vitamin recommendations: The recommendations for patients receiving total parenteral nutrition are listed in Table 4. 46 ACKNOWLEDGMENTS: The authors thank the Medical Research Council ofCanada for the Fellowship award to Michel Lem~e and for financial support of the work described (MA. #7923), and Janet Chrupala for her expert typing. REFERENCES 1 Cahill GF: Starvation in man. N Engl J Med 1970; 282:668-75 2 Kinney JM, Elwyn DU. Protein metabolism and injury. Ann Rev Nutr 1983; 3:433-66 3 Clowes GHA, George BC, Villee CA, Saravis CA. Muscle proteolysis induced by a circulating peptide in patients with sepsis or trauma. N Eng} J Med 1983; 308:545-52 4 Cuthbertson D~ Observations on disturbance of metabolism produced by injury to limbs. Quart J Med 1932; 25:233-46 5 Cuthbertson DE The metabolic response to injury and its nutritional implications: retrospect and prospect. JPEN 1979; 3:108-29 6 Munro HN. General aspects ofthe regulation of protein metabolism by diet and hormones. In: Mammalian protein metabolism (vol 1), Munro HN, Allison JB, eds. New York: Academic Press, 1964; 381-481 7 Long CL, Jeevanandam B, Kim BM, Kinney JM. Whole body protein synthesis and catabolism in septic man. Am J Clio Nutr 1977; 30:1340 8 Long CL, Spencer JL, Kinney JM, Geiger JW: Carbohydrate metabolism in man: effect ofelective operations and major injury. J Appl Physiol1971; 31:110-16 9 Gump FE, Long CL, Killian ~ Kinney JM. Studies of glucose intolerance in septic injured patients. J Uauma 1974; 14:378-88 10 Duke JU, Jorgensen SB, Bmell JR, Long CL, Kinney JM. Contribution of protein to calorie expenditure following injury. Surgery 1970; 68:168-74 11 Uegsted OM. Energy requirements. In: Present knowledge in nutrition. Washington, D.C.: The Nutrition Foundation, 1984; 1-6 12 McNeill KG, Mernagh JR, Jeejeebhoy leN, Wolman SL, Harrison JR. In vivo measurements of body protein based on the determination of nitrogen by prompt gamma analysis. Am J Clin Nutr 1979; 32:1955-61 13 McNeill KG, Mernagh JR, Harrison JE, Stewart S, Jeejeebhoy KN. Changes in body protein, body potassium and lean body mass during total parenteral nutrition. JPEN 1982; 6:106-08 14 Saba TM, Dillon BC, Lanser ME. Fibronectin and phagocytic host defense: relationship to nutritional support. JPEN 1983; 7:62-8 15 Howard L, Dillon BC, Saba TM, Hofmann S, Cho E. Decreased plasma fibronectin during starvation in man. JPEN 1984; 8:237-44 16 lWomey ~ Ziegler D, Rombeau J. Utility of skin testing in nutritional assessment: a critical review. JPEN 1982; 6:50-8 17 Mullen IL, Buzby G~ Matthews DC, Smale BF, Rosato EF: Reduction of operative morbidity and mortality by combined preoperative and post-operative nutritional support. Ann Surg 1980; 192:604-13 18 Rombeau J, Bamt LR, Williamson CE, Mullen JL. Preoperative
574
total parenteral nutrition and surgical outcome in patients with in8ammatory bowel disease. Am J Surg 1982; 143:139-43 19 Brough W, Horne H, Blount A, Jeejeebhoy KN. The effect of nutrient intake, surgery, sepsis, trauma and chronic steroid administration on muscle function. (in preparation) 20 Lopes j, Russell DMcR, Whitwell j, jeejeebhoy KN. Skeletal muscle function in malnutrition. Am J Clin Nutr 1982; 36:602-10 21 Russell DMcR, Leiter LA, Whitwell j, Marliss EB, jeejeebhoy KN. Skeletal muscle function during hypocaloric diets and fasting: a comparison with standard nutritional assessment parameters. Am J Clin Nutr 1983; 37:133-38 22 Russell DMcR, Prendergast Pj, Darby PE, Garfinkel PE, Whitwell J, Jeejeebhoy KN. A comparison between muscle function and body composition in anorexia nervosa: the effect of refeeding. Am J Clin Nutr 1983; 37:229-37 23 Edwards RH1: Young A, Hosking G~ Human skeletal muscle function description of tests and normal values. Clin Sci Mol Med 1977; 52:283-90 24 Moxham J, Morris AJR, Spiro SG, Edwards RIn Green M. Contractile properties and fatigue of the diaphragm in man. Thorax 1981; 36:164-68 25 Kelly SM, Rosa A, Field S, Coughlin M, Shizgal HM, Macklem YI: Respiratory muscle strength and body composition in patients receiving total parenteral nutrition therapy. Am Rev Respir Dis 1984; 130:33-7 26 Arora NS, Rochester DR Respiratory muscle strength and maximum voluntary ventilation in undernourished patients. Am Rev Respir Dis 1982; 126:5-8 27 Fraser 1M, Russell DMcR, Whittaker JS, Zamel N, Goldstein R, Jeejeebhoy KN. Skeletal and diaphragmatic muscle function in malnourished patients with chronic obstructive lung disease. Am Rev Respir Dis 1984; 129:A269 28 Berkelhammer CH, Baker J~ Jeejeebhoy KN. Skeletal muscle function in chronic renal failure: a valid test of nutritional status. Clin Invest Med 1984; 7:(suppI2):72 29 Russell DMcR, Atwood HL, Whittaker JS, Itakura 1: Walker PM, Mickle DAG, et ale The effects of fasting and hypocaloric diets on the functional and metabolic characteristics of rat gastrocnemius muscle. Clin Sci 1984; 67:185-94 30 Russell DMcR, Walker PM, Leiter LA, Sima AAF, Tanner WK, Mickle DAG, et ale Metabolic and structural changes in skeletal muscle during hypocaloric dieting. Am J Clin Nutr 1984; 39:503-13 31 Whittaker JS, Desai M, Atwood UL, Walker PM, Jeejeebhoy leN. Effect of hypocaloric feeding and refeeding on rat soleus muscle function and composition. Clin Res 1984; 32:479A 32 Greenberg GR, jeejeebhoy KN. Intravenous protein-sparing therapy in patients with gastrointestinal disease. JPEN 1979; 3:427-32 33 Collins J~ Oxby CB, Hill GL. Intravenous amino acids and intravenous hyperalimentation as protein-sparing therapy after major surgery: a controlled clinical trial. Lancet 1978; 1:788-91 34 Anderson GH, Patel DG, Jeejeebhoy KN. Design and evaluation by nitrogen balance and blood amioograms of an amino acid mixture for total parenteral nutrition of adults with gastrointestinal disease. J Clio Invest 1974; 53:904-12 35 Harris]A, Benedict FG. Standard basal metabolism constants for physiologists and clinicians. In: A biometric study of basal metabolism in man. Carnegie Institute of Washington, publication 279. Philadelphia: JB Lippincott, 1919; 233-50 36 Shike M, Russell DMcR, Detsky AS, Harrison JE, McNeill KG, Shepherd FA, et ale Changes in body composition in patients with small cell lung cancer. The effect oftotal parenteral nutrition as an adjunct to chemotherapy. Ann Intern Med 1984; 101: 303-39 37 Elwyn DH, Gump FE, Munro UN, Iles M, Kinney JM. PaIenteraI Nutrition In CrtIicaIIy II (LMnoyne, JeelNbhof)
Changes in nitrogen balance ofdepleted patients with increasing infusions of glucose. Am J Clio Nutr 1979; 32:1597-1611 38 Roulet M, Detsky AS, Marliss EB, Todd TRJ, Mahon WA, Anderson GU, et ale A controlled trial of the effect ofparenteral nutritional support on patients with respiratory failure and sepsis. Clin Nutr 1983; 2:97-105 39 Askanazi J, Carpentier YA, Elwyn DH, Nordenstrom J, Jeevanandam M, Rosenbaum SH, et ale Influence of total parenteral nutrition on fuel utilization in injury and sepsis. Ann Surg 1980;
191:40-6
40 Baker J~ Detsky AS, Stewart S, Whitwell J, Marliss EB, Jeejeebhoy KN. A randomized trial of total parenteral nutrition in critically ill patients: metabolic effects ofvarying glucose-lipid ratios as the energy source. Gastroenterology 1984; 87:53-9 41 MacFie J, Smith RC, Hill GL. Glucose or fat as a non-protein energy source? A controlled clinical trial in gastroenterological patients requiring intravenous nutrition. Gastroenterology 1981;
80:103-07
42 Jeejeebhoy KN, Anderson GH, Nakhooda AF, Greenberg GR,
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