The Malnourished Patient: Nutritional Assessment And

THE MALNOURISHED PATIENT : NUTRITIONAL ASSESSMENT AND MANAGEMENT

Samuel Klein and Khursheed N. Jeejeebhoy

BASIC NUTRITIONAL CONCEPTS, 265 MALNUTRITION, 271 Refeeding Syndrome, 277 Energy Stores, 265 Specific Nutrient Deficiencies, 271 Clinical Recommendations, 278 Energy Metabolism, 265 Protein-Energy Malnutrition, 272 PATIENTS WITH SEVERE MALABSORP- Protein, 266 Effect of Protein-Energy Malnutrition on TION, 279 Carbohydrate, 268 Tissue Mass and Function, 273 Clinical Considerations, 279 Lipids, 268 Nutritional Assessment Techniques, 274 Treatment, 280 Major Minerals, 268 REFEEDING THE MALNOURISHED PA- TIENT, 277 Micronutrients, 268 STARVATION, 271

Ingestion and absorption of a nutritionally adequate diet is Energy Metabolism necessary to maintain normal body composition and function. Gastrointestinal (GI) diseases can cause malnutrition by Energy is continuously required for normal organ function, affecting nutrient intake, nutrient absorption, or nutrient re- maintenance of metabolic homeostasis, heat production, and quirements . Therefore, it is important for gastroenterologists performance of mechanical work. Total daily energy expend- to understand the principles involved in evaluating and treat- iture (TEE) is composed of resting energy expenditure (nor- ing malnourished patients . mally -70% of TEE), thermic effect of feeding (normally -10% of TEE), and energy expenditure of physical activity (normally -20% of TEE) . BASIC NUTRITIONAL CONCEPTS Resting Energy Expenditure Energy Stores Resting energy expenditure (REE) represents postabsorptive Endogenous energy stores are continuously oxidized for fuel . energy expenditure while a person lies quietly awake . Dur- Triglyceride present in adipose tissue is the major fuel re- ing these conditions, approximately I kcal/kg body weight is serve in the body and is critical for survival during periods consumed per hour in healthy adults . The energy require- of starvation (Table 15-1) . The high energy density and ments of specific tissues differ dramatically (Table 15-2) . hydrophobic nature of triglycerides make it a fivefold better The liver, gut, brain, kidneys, and heart constitute approxi- fuel per unit mass than glycogen . Triglycerides liberate 9 .3 mately 10% of total body weight but account for approxi- kcal/g when oxidized and are compactly stored as an oil mately 75% of the REE . In contrast, resting skeletal muscle inside the fat cell, accounting for 85% of adipocyte weight . consumes approximately 20% of REE but represents approx- In comparison, glycogen produces only 4 .1 kcal/g on oxida- imately 40% of body weight, and adipose tissue consumes tion and is stored intracellularly as a gel, containing approxi- less than 5% of REE but usually accounts for more than mately 2 g of water for every gram of glycogen . Adipose 20% of body weight . tissue is unable to provide fuel for certain tissues, such as Several equations have been generated to estimate resting bone marrow, erythrocytes, leukocytes, renal medulla, eye energy requirements 2-5 (Table 15-3). The equations for tissues, and peripheral nerves, which cannot oxidize lipids healthy subjects generate values that are usually within 10% and require glucose for their energy supply . During endur- of measured values . However, these equations are much less ance exercise, glycogen and triglycerides present within accurate in persons who are at extremes in weight (either muscle tissue provide an important source of fuel for work- very lean or obese) or who are ill because alterations in ing muscles .' body composition and metabolic stress influence energy ex- 265 pir

TIt fR t OGY

Table 15-1 1 Endogenous Fuel Stores in a Man Weighing followed by carbohydrate and then fat . A meal containing all 70 kg these nutrients usually increases metabolic rate by 5% to 10% of ingested or infused calories . MASS

TISSUE FUEL SOURCE Grams Kilocalories Recommended Energy Intake in

Adipose Triglyceride 13,000 120,000 os i l z d t e s Liver Glycogen 100 400 Protein 300 1200 We developed a simple method for estimating total daily Triglyceride 50 450 energy requirements in hospitalized patients based on body Protein 6000 24,000 Muscle mass index (BMI)A (Table 15-6) . In general, energy given Glycogen 400 1600 Triglyceride 250 2250 per kilogram body weight is inversely related to BMI . Blood Glucose 3 12 Triglyceride 4 35 Free fatty acids 0 .5 5 Protein

Proteins are composed of amino acids, which are nitrogen- penditure. Malnutrition and hypocaloric feeding decrease containing compounds . Twenty different amino acids are REE to values 15% to 20% below those expected for actual commonly found in human proteins . Some amino acids (his- body size, whereas metabolic stress, such as inflammatory tidine, isoleucine, leucine, lysine, methionine, phenylalanine, diseases or trauma, often increases energy requirements . threonine, tryptophan, valine, and possibly arginine) are con- However, it is rare for most illnesses to increase REE by sidered essential because their carbon skeletons cannot be more than 50% of pre-illness values . For example, patients synthesized by the body. Other amino acids (glycine, ala- with Crohn's disease who do not have an infectious compli- nine, serine, cysteine, cystine, tyrosine, glutamine, glutamic cation have normal metabolic rates6 whereas patients with acid, asparagine, and aspartic acid) are nonessential because severe bums may have a 40% increase in REE.7 they can be made from endogenous precursors or essential amino acids . In disease states, nonessential amino acids may become essential . For example, it has been shown that cyste- Energy Expenditure of Physical Activity ine is essential in patients with cirrhosis 9 because the trans- sulfuration pathway is impaired in these patients . The effect of physical activity on energy expenditure de- The body of an average 75-kg male contains approxi- pends on the intensity and duration of daily activities . mately 12 kg of protein and 2 kg of nitrogen . In contrast to Highly trained athletes can increase their TEE 10- to 20-fold fat and carbohydrate, there is no storage depot for protein, during athletic events. The activity factors shown in Table so excess intake is catabolized and the nitrogen component 15-4, expressed as a multiple of REE, can be used to is excreted . Inadequate protein intake causes net nitrogen estimate TEE in active patients . The energy expended during losses, initially from organs such as the liver and then from physical activity is equal to : muscle mass . Data from nitrogen balance studies suggest that the mean daily protein requirement for adults is 0 .6 g/kg (REE) X (activity factor) (with a standard deviation of 12 .5%). Therefore, a protein X (duration of activity in hours/24 h) . intake of 0 .75 g/kg would meet the requirements of 97% of TEE represents the summation of energy expended during the adult population. However, this amount is based on studies in which a reference protein containing a large propor- all daily activities, including rest periods (Table 15-5) . tion of essential amino acids was used. Requirements for dietary protein of lesser biologic value may be higher . Intra- Thermic Effect of Feeding venously administered amino acids are as effective in maintaining nitrogen balance as oral protein of the same amino Eating or infusing nutrients increases metabolic rate . Dietary acid composition . 1 ° protein causes the greatest stimulation of metabolic rate, Individual protein requirements are affected by several

Table 15-2 1 Resting Energy Requirements of a Man Weighing 70 kg

TISSUE MASS ENERGY CONSUMED

Percentage Kilocalories/gram Percentage TISSUE Grams Body Weight of Tissue per Day Kilocalories/Day REE

Liver 1550 2 .2 0.28 445 19 Gut 2000 3 .0 0.15 300 13 Brain 1400 2 .0 0.30 420 18 Kidneys 300 0.4 1 .27 360 15 Heart 300 0.4 0.80 235 10 Skeletal muscle 28,000 40 .0 0.014 400 18 Adipose 15,000 21 .0 0.005 80 4

REE, resting energy expenditure .

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Table 15-3 1 Commonly Used Formulas for Calculating Table 15-5 1 Daily Energy Requirements in Humans Resting Metabolic Rate REE ACTIVITY TEE HARRIS-BENEDICT EQUATION AGE (Yr) (kcal/kg) FACTOR (kcal/kg) Men : 66+(13 .7X W)+(5 X H)-(6 .8XA) Male Women : 11-14 32 .0 1 .70 55 665+(9 .6X W)+(1 .8x H)-(4 .7xA) 15-18 26 .7 1 .67 45 WORLD HEALTH ORGANIZATION 19-25 24 .7 1 .67 40 25-50 22 .8 1 .60 37 Age (Years) Male Female 19 .8 1 .50 30 0-3 (60 .9 X W) - 54 (61 .0X W) - 51 >51 Female 3-10 (22 .7 X W) - 495 (22 .5 x W) + 499 11-14 28 .5 1 .67 47 10-18 (17 .5 X W) + 651 (12 .2 X W) + 746 15-18 24 .9 1 .60 40 18-30 (15 .3 X W) + 679 (14 .7 x W) + 996 19-24 23 .2 1 .60 38 30-60 (11 .2 X W) + 879 (8 .7 x W) + 829 25-50 21 .9 1 .55 36 >60 (13 .5 X W) + 987 (10 .5 x W) + 596 >51 19 .7 1 .50 30 OWEN ET AL . Men : REE, resting energy expenditure; TEE, total daily energy expenditure . 879 + (10 .2 X W) Women : 795 + (7 .18 X W) IRETON-JONES ET AL . ments should be in the form of essential amino acids in Spontaneously breathing : normal adults. 629 - (11 X A) + (25 X W) - (609 X Q) Ventilator dependent: 1925 - (10 X A) + (5 X W) + (281 XG)+(292XT) + (851 X B) Nitrogen Balance

A, age in years ; B, diagnosis of burn (present = 1, absent = 0) ; G, gender (male = 1, female = 0); H, height in centimeters ; 0, obesity (present = 1, absent Nitrogen balance is calculated as the difference between ni- = 0) ; T, diagnosis of traumas (present = 1, absent = 0) ; W, weight in kilograms . trogen intake, in the form of amino acids or protein, and nitrogen losses in urine, stool, skin, and body fluids . Nitro- gen balance can be used to estimate protein balance because factors, such as the amount of nonprotein calories provided, approximately 16% of protein consists of nitrogen and it is overall energy requirements, protein quality, and the pa- assumed that all body nitrogen is incorporated into protein . tient's nutritional status (Table 15-7) . Protein requirements A positive balance (intake greater than losses) represents increase when calorie intake does not meet energy needs . anabolic conditions and a net increase in total body protein, The magnitude of this increase is directly proportional to the whereas a negative balance demonstrates net protein catabo- decrease in energy supply . Conversely, at any level of sub- lism. For example, a negative nitrogen balance of 1 g/day optimal protein intake, nitrogen balance can be improved by represents a 6 .25 g/day (16% of 6.25 g protein = 1 g increasing energy intake. Therefore, nitrogen balance reflects nitrogen) loss of body protein, which is equivalent to a 30 g/ both protein intake and energy balance . Fasting animals and day loss of hydrated lean tissue . In practice, nitrogen balance humans excrete nitrogen at rates that are proportional to studies tend to be artificially positive because of overestima- their metabolic rates and is estimated to be approximately 2 tion of dietary nitrogen intake and underestimation of losses mg N/kcal of REE.t t Illness, by increasing catabolism and caused by incomplete urine collections and unmeasured out- metabolic rate, also increases requirements for protein (see puts. Table 15-7) . Protein requirements are also determined by It is important to consider the patient's recent protein the availability of adequate amounts of essential amino acids intake and nutritional status in interpreting nitrogen balance in the protein source. Inadequate amounts of any of the data. When a person ingesting a low-protein diet is re-fed essential amino acids result in inefficient utilization . In gen- protein, nitrogen excretion does not rise proportionately to eral, approximately 15% to 20% of total protein require- intake and there is retention of administered nitrogen . This

Table 15-6 1 Estimated Energy Requirements Factors Used to Estimate Thermic Effect Table 15-4 1 for Hospitalized Patients Based on Body Physical Activity of Mass Index ACTIVITY ACTIVITY BMI (kg/m 2) ENERGY REQUIREMENTS (kcal/kg/day)* LEVEL EXAMPLES FACTOR <15 35-40 Resting 1 .0 15-19 30-35 Very light Standing, driving, typing 1 .1-2 .0 20-29 20-25 Light Walking 2-3 mph, shopping, light 2 .1-4 .0 ?30 15-20 housekeeping Walking 3-4 mph, biking, gardening, 4 .1-6 .0 Moderate *These values are recommended for critically ill patients and all obese pa- scrubbing floors tients ; add 20% of total calories in estimating energy requirements in non-criti- Heavy Running, swimming, climbing, bas- 6 .1-10 .0 cally ill patients . ketbal I BMI, body mass index . The lower range within each BMI category should be considered in insulin- Adapted from Alpers DA, Stenson WE, Bier DM . Manual of Nutritional Thera- resistant or critically ill patients to decrease the risk of hyperglycemia and infec- peutics . Boston : Little, Brown, 1995 . tion associated with overfeeding .

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for steroid hormone, prostaglandin, thromboxane, and leuko-e triene synthesis ; structural components of cell membranes' PROTEIN REQUIREMENTS and carriers of essential nutrients . Dietary lipids are com- CLINICAL CONDITION (g/kg IBW/day) posed mainly of triglycerides, which contain saturated and Normal 0 .75 unsaturated long-chain fatty acids of 16 to 18 carbon chains Metabolic stress 1 .0-1 .5 in length. The use of fat as a fuel requires the hydrolysis o Hemodialysis 1 .2-1 .4 endogenous or exogenous triglycerides and cellular uptake of Peritoneal dialysis 1 .3-1 .5 released fatty acids . Long-chain fatty acids are delivered IBW, ideal body weight . across the outer and inner mitochondrial membranes by a Additional protein requirements are needed to compensate for excess protein carnitine-dependent transport system ." Once inside the mito- loss in specific patient populations, such as patients with burn injuries, open chondria, fatty acids are degraded by beta oxidation to acetyl wounds, and protein-losing enteropathy or nephropathy . Lower protein intake may be necessary in patients with chronic renal insufficiency not treated by dialysis coenzyme A (CoA), which then enters the tricarboxylic and certain patients with liver disease and hepatic encephalopathy . acid cycle . Therefore, the ability to use fat as a fuel depends on normal functioning mitochondria . A decrease in the number of mitochondria or oxidative enzymes, associated gain during early refeeding is caused by a rapid accumula- with aging or deconditioning, favors the use of carbohydrate tion of nitrogen in the liver and, to a lesser extent, in as a fuel ." kidneys and muscle . However, the early retention of nitrogen is not sustained and decreases markedly within 4 to 7 days . In contrast, when a person ingesting a high-protein diet de- Essential Fatty Acids creases protein intake, the previously high urinary nitrogen loss continues for a few days despite the reduced intake, Most fatty acids can be synthesized by the liver, but humans resulting in a negative nitrogen balance . Similarly, initial nitrogen loss after injury is greater in well-nourished than in lack the desaturase enzyme needed to produce the n-3 (dou- malnourished patients . Therefore, a "labile" nitrogen pool of ble bond between carbons 3 and 4 counted from the methyl approximately 60 g contributes to short-term alterations in end) and n-6 (double bond between carbons 6 and 7) fatty nitrogen balance and makes short-term nitrogen balance acid series. Linoleic acid (C18 :2, n-6) should constitute a measurements an unreliable method for determining optimal least 2% and linolenic acid (C18 :3, n-6,9,12) at least 0 .5% protein intake. of the daily caloric intake to prevent the occurrence of essential fatty acid deficiency (EFAD) . Before the advent of Carbohydrate parenteral nutrition, a clinical syndrome of EFAD, manifested as a rash and a specific alteration in the plasma fatty Approximately 400 g of digestible carbohydrates are eaten acid profile, was recognized only in infants . Adults did not each day in a normal diet : 60% as starch (polysaccharide seem to demonstrate this syndrome because of sufficient made from maize, rice, wheat, and potato) ; 30% as sucrose essential fatty acids stores in adipose tissue . The use of (disaccharide made from sugar cane and beet sugar) ; and total parenteral nutrition given as a continuous infusion 10% as lactose (disaccharide made from milk). In addition, of a fat-free hypertonic glucose solution led to EFAD in approximately 10 to 20 g of indigestible carbohydrate (solu- adults, and the plasma pattern of EFAD was observed as ble and insoluble fibers) are consumed daily . Complete di- early as 10 days after glucose-based total parenteral gestion of the principal dietary carbohydrates generate nutrition was started, before the onset of any clinically monosaccharides (glucose, fructose, and galactose) . All cells observable features . 19 The increase in plasma insulin con- are able to generate energy (adenosine triphosphate) by me- centrations caused by total parenteral nutrition is presum- tabolizing glucose to either three-carbon compounds via gly- ably responsible for EFAD because insulin inhibits lipoly- colysis or to carbon dioxide and water via glycolysis and the sis and, therefore, the release of endogenous essential fatty tricarboxylic acid cycle . acids . There is no dietary requirement for carbohydrate because glucose can be synthesized from endogenous amino acids and glycerol. Nevertheless, carbohydrate is an important fuel Major Minerals because of the interactions between carbohydrate and protein metabolism. Carbohydrate intake stimulates insulin secretion, Major minerals are inorganic nutrients that are required in which inhibits muscle protein breakdown,' 2 stimulates mus- large (>100 mg/day) quantities and are important for ionic cle protein synthesis, 13 and decreases endogenous glucose equilibrium, water balance, and normal cell function . Malnu- production from amino acids. 14 In addition, glucose is the trition and nutritional repletion can have dramatic effects on required or preferred fuel for red and white blood cells, the major mineral balance . Evaluation of macromineral defi- renal medulla, eye tissues, peripheral nerves, and the brain . ciency and recommended dietary intake for healthy adults However, once glucose requirements for these tissues (-150 are shown in Table 15-8 . g/day) are met, the protein-sparing effects of carbohydrate and fat are similar. 15, 16

Lipids Micronutrients

Lipids consist of triglycerides (fat), sterols, and phospholip- Micronutrients consist of trace elements and vitamins . Both ids. These compounds serve as sources of energy ; precursors forms of micronutrients are essential because, as constituents

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Table 15-8 ~ Major Mineral Requirements and Assessment of Deficiency

LABORATORY EVALUATION SYMPTOMS OR SIGNS MINERAL ENTERAL PARENTERAL OF DEFICIENCY Comment

Sodium 0.5-5 g 60-150 mmol Hypovolemia, weakness Urinary sodium May not reflect body stores ; clinical evaluation is best Potassium 2-5 g 60-100 mmol Weakness, paresthesias, ar- Serum potassium May not reflect body stores rhythmias Magnesium 300-400 mg 5-15 mmol Weakness, twitching, let- Serum magnesium May not represent body stores any, arrhythmias, hypo- calcemia Urinary magnesium May not represent body stores Calcium 800-1200 mg 5-15 mmol Osteomalacia, tetany, ar- 24-hr urinary calcium Reflects recent intake rhythmias Dual energy x-ray absorp- Reflects bone calcium content tiometry Phosphorus 800-1200 mg 20-60 mmol Weakness, fatigue, leuko- Plasma phosphorus May not reflect body stores cyte and platelet dysfunction, hemolytic anemia, cardiac failure, and decreased oxygenation

of enzyme complexes, they regulate metabolic processes and requirements that are considerably higher than the recom- substrate metabolism . The recommended dietary intake for mended dietary intake . trace elements and vitamins (Tables 15-9 and 15-10) is set at two standard deviations above the estimated mean so that it covers the needs of 97% of the healthy population . There- Trace Elements fore, the recommended dietary intake exceeds the micronutrient requirements of most persons . However, patients with Trace minerals are inorganic nutrients that are required in disease, particularly those who have decreased GI absorptive small (<100 mg/day) quantities (see Table 15-9) . Fifteen function and increased micronutrient GI losses, may have elements have been found to be essential for health in

Table 15-9 J Trace Mineral Requirements and Assessment of Deficiency

LABORATORY EVALUATION SYMPTOMS OR SIGNS MINERAL ENTERAL PARENTERAL OF DEFICIENCY Comment

Chromium 30-200 Ag 10-20 Ag Glucose intolerance, periph- Serum Does not reflect body stores eral neuropathy, encephalopathy Glucose tolerance test Not specific Copper 2 mg 0.3 mg Anemia, neutropenia, osteo- Serum copper Insensitive for body stores porosis, diarrhea Plasma ceruloplasmin Acute phase reactant Iodine 150 ug 70-140 ug Hypothyroidism, goiter Urine iodine Reflects recent intake Thyroid stimulating hormone Reflects thyroid function Iron 10-15 mg 1-1 .5 mg Microcytic hypochromic Serum iron and total iron Poor measure of body stores; anemia binding capacity high specificity when levels low; poor sensitivity Manganese 1 .5 mg 0.2-0.8 mg* Hypercholesterolemia, de- Serum manganese Does not reflect body stores mentia, dermatitis Selenium 55 ag 20-40 sg Cardiomyopathy (Keshan's Serum selenium Insensitivity for body stores disease), muscle weakness Blood glutathione peroxidase More sensitive for body activity stores Zinc 15 mg 2 .5-4 mg Growth retardation, delayed Plasma zinc Poor specificity for body sexual maturation, hypo- stores gonadism, alopecia, acro- orificial skin lesion, diarrhea, mental status changes

*Recent evidence suggests that manganese toxicity, manifested as extrapyramidal and parkinsonian-like symptoms, can occur in patients with chronic liver disease or those receiving long-term parenteral nutrition . Many clinicians now limit manganese addition to parenteral nutrition solutions to < 0 .1 mg/d or eliminate it entirely (see reference 21 ).

Table 15-10 1 Vitamin Requirements and Assessment of Deficiency

LABORATORY EVALUATION SYMPTOMS OR SIGNS VITAMIN ENTERAL PARENTERAL OF DEFICIENCY Test Comment

A (retinol) 5000 IU 3300 IU Night blindness, Bitot's spots, Serum retinal keratomalacia, follicular hyperkeratosis, xerosis D (ergocalciferol) 400 IU 200 IU Rickets, osteomalacia, osteo- Serum 25-hydroxyvi- porosis, bone pain, muscle tamin D weakness, tetany E (alpha-tocopherol) 33 IU 33 IU Hemolysis, retinopathy, neu- Serum tocopherol ropathy Serum tocopherol : total lipid ratio K (phylloquinone) 50-100 µg 100 µg Easy bruising and bleeding, Prothrombin time Not specific for vita- abnormal clotting min 1 B, (thiamine) 1-1 .5 mg 3 mg Beriberi, cardiac failure, RBC transketolase ac- Reflects body stores Wernicke's encephalopa- tivity thy, peripheral neuropathy, fatigue, ophthalmoplegia B2 (riboflavin) 1 .1-1 .8 mg 3 .6 mg Cheilosis, sore tongue and RBC glutathione re- Reflects body stores mouth, eye irritation, seb- ductase activity horrheic dermatitis B3 (niacin) 12-20 mg 40 mg Pellagra (dermatitis, diarrhea, Urinary N-methyl-nic- Reflects recent intake dementia), sore mouth and otinamide tongue B5 (pantothenic acid) 5-10 mg 10 mg Fatigue, weakness, paresthe- Urinary pantothenic Reflects recent intake sias, tenderness of heels acid and feet B6 (pyridoxine) 1-2 mg 4 mg Sebhorrheic dermatitis, chei- Plasma pyridoxal Reflects body stores losis, glossitis, peripheral phosphate neuritis, convulsions, hypochromic anemia B7 (biotin) 100-200 µg 60 µg Sebhorrheic dermatitis, alope- Plasma biotin cia, change in mental status, seizures, myalgia, hyperesthesia B9 (folic acid) 400 µg 400 µg Megaloblastic anemia, glossi- Serum folic acid Reflects body stores tis, diarrhea and recent intake RBC folic acid Reflects body stores B12 (cobalamin) 3 µg 5 µg Megaloblastic anemia, pares- Serum cobalamin Reflects body stores thesias, decreased vibratory or position sense, ataxia, mental status changes, diarrhea Serum methylmalonic Tests functional block acid in enzyme C (ascorbic acid) 75-90 mg 100 mg Scurvy, petechia, purpura, Plasma ascorbic acid Reflects recent intake (125 mg gingival inflammation and in smokers) bleeding, weakness, de- pression Leukocyte ascorbic Reflects recent stores acid

RBC, red blood cell .

animals: iron, zinc, copper, chromium, selenium, iodine, Vitamins cobalt, manganese, nickel, molybdenum, fluorine, tin, sili- con, vanadium, and arsenic . However, according to the Vitamins are organic compounds that are required in small strict criteria suggested by Cotzias, 20 only the first seven (<100 mg/day) quantities (see Table 15-10) . A negative have been shown to be necessary for health in humans . balance between vitamin intake and vitamin utilization plus Recent data suggest that the recommended daily parenteral losses causes clinical symptoms of vitamin deficiency . The intake for manganese may be too high in patients with amount of time before the onset of clinical manifestations chronic liver disease or those receiving long-term parenteral depends on the cumulative negative vitamin balance and the nutrition because of excessive manganese deposition in basal size of available vitamin stores . In general, water-soluble ganglia, causing extrapyramidal and Parkinson-like symp- vitamin body stores are much smaller than fat-soluble vita- toms.21 min stores, and so the onset of symptoms is more rapid for THE MALNCLJRL"H[1) PAn NT : NUTRITION A[ AS water-soluble than for fat-soluble vitamin deficiency . Blood core production decreases to approximately 75 g/day, pro- test results usually become abnormal before the onset of viding fuel for glycolytic tissues (40 g/day) and the brain clinical manifestations and can be used to assess the need (35 g/day) while maintaining constant plasma glucose con- for supplementation (see Table 15-10) . centration . Energy expenditure decreases by 20% to 25% at 30 days of fasting31 and remains relatively constant thereaf- ter despite continued starvation. STARVATION The metabolic response to short-term and long-term starvation differs between lean and obese persons . Obesity is During starvation, a complex and carefully integrated series associated with a blunted increase in lipolysis and decrease of metabolic alterations decrease metabolic rate, maintain in glucose production compared with that in lean persons.32, 33 glucose homeostasis, conserve body nitrogen, and increase In addition, protein breakdown and nitrogen losses are less the use of adipose tissue triglycerides to meet energy needs . in obese than lean persons, thereby helping conserve muscle During the first 24 hours of fasting, hepatic glucose produc- protein.34 tion and oxidation decrease, whereas whole-body lipolysis The events that mark the terminal phase of starvation and ketone body production increase .22 The relative contribu- have been studied extensively in rats . Body fat mass, muscle tion of gluconeogenesis to hepatic glucose production in- protein, and the sizes of most organs are markedly decreases as the rate of hepatic glycogenolysis declines ; at 24 creased . The weight and protein content of the brain, how- 23 hours of fasting, only 15% of liver glycogen stores remain . ever, remain relatively stable throughout starvation . During Glucose is oxidized predominantly by the brain and glucose- this final phase of starvation, body fat stores reach a critical requiring tissues, accounting for approximately 20% of total level, energy derived from body fat decreases, and muscle energy consumption . The oxidation of fatty acids released protein catabolism is accelerated . Death commonly occurs from adipose tissue triglycerides accounts for approximately when there is a 30% loss of muscle protein .35 The mecha- 65% of energy consumed during the first 24 hours of fast- nisms responsible for death from starvation in humans are . Approximately 15% of resting energy requirements is ing not well understood . In general, the duration of survival provided by the oxidation of protein; 70 g of amino acids during starvation depends on the amount of available body are mobilized from protein stores, and 10 g of nitrogen are fuels and lean body mass . The possibility that there are .24 excreted in urine lethal levels of body weight loss (loss of 40% of body During short-term starvation (1-14 days of fasting), the weight), 36 of protein depletion (loss of 30%-50% of body decline in plasma insulin, increase in plasma epinephrine, protein),37 of fat depletion (loss of 70%-95% of body fat and increase in lipolytic sensitivity to catecholamines stimu- stores)," or of body size (body mass index of 13 for men late adipose tissue lipolysis 25 . 26 The increase in fatty acid and 11 for women) 39 has been proposed . In normal-weight delivery to the liver, in conjunction with an increase in the men, death occurs after approximately 2 months of starva- ratio of plasma glucagon :insulin concentration, enhances the tion, when more than 35% (-25 kg) of body weight is production of ketone bodies by the liver .27 A maximal rate lost.38 In contrast, obese persons have undergone therapeutic of ketogenesis is reached by 3 days of starvation, and fasts for more than a year without adverse consequences . plasma ketone body concentration is increased 75-fold by 7 The longest reported fast was that of a 207 kg man who days. In contrast to fatty acids, ketone bodies can cross the blood-brain barrier and provide most of the brain's energy ingested acaloric fluids, vitamins, and minerals for 382 days needs by 7 days of starvation .28 The use of ketone bodies by and lost 61% (126 kg) of his initial weight.40 the brain greatly diminishes glucose requirements and thus spares the need for muscle protein degradation to provide glucose precursors. If early protein breakdown rates were to MALNUTRITION continue throughout starvation, a potentially lethal amount of muscle protein would be catabolized in less than 3 weeks. A normal nutritional status represents a healthy balance be- Whole-body glucose production decreases by more than half tween nutrient intake and nutrient requirements. Malnutrition during the first few days of fasting because of a marked represents a continuum of events caused by nutrient disequi- reduction in hepatic glucose output . As fasting continues, the librium, which alters intermediary metabolism, organ func- conversion of glutamine to glucose in the kidney represents tion, and finally body composition . Therefore, in a general almost 50% of total glucose production . Energy is conserved sense, malnutrition can be defined as any metabolic, func- by a decrease in physical activity caused by fatigue and a tional, or compositional alteration caused by inadequate nu- reduction in REE caused by increased conversion of active trient intake. Malnutrition can be caused by specific nutrient thyroid hormone to its inactive form,29 and suppressed sym- deficiencies and a more generalized deficiency in protein and pathetic nervous system activity .30 energy. During long-term starvation (14-60 days of fasting), maximal adaptation is reflected in a plateau in lipid, carbohydrate, and protein metabolism . The body relies almost Specific Nutrient Deficiencies entirely on adipose tissue for its fuel, which provides more than 90% of daily energy requirements . Muscle protein A careful history and physical examination, routine blood breakdown decreases to less than 30 g/day, causing a tests, and selected laboratory tests can be used to diagnose marked decrease in urea nitrogen production and excretion . specific macronutrient, major mineral, vitamin, and trace The decrease in osmotic load diminishes urine volume to mineral deficiencies (see Tables 15-8 to 15-11) . Replace- 200 mL/day, thereby limiting fluid requirements. Total glu- ment of the deficient nutrient usually corrects the biochemi-

Table 15-11 1 Selected Symptoms and Signs tional therapy. However, prolonged primary PEM can cause of Nutritional Deficiencies irreversible changes in organ function and growth . Second- ary PEM is caused by illness or injury, which alter appetite, ORGAN SYMPTOMS OR POSSIBLE NUTRIENT digestion, absorption, or nutrient metabolism . Wasting disor- SYSTEM SIGNS DEFICIENCY ders, such as cancer, acquired immunodeficiency syndrome, Skin Pallor Iron, folate, vitamin B 72 and rheumatologic diseases, are characterized by involuntary Follicular hyperkera- Vitamins A and C loss of body weight and muscle mass in the setting of a tosis chronic illness. These patients often experience wasting be- Perifollicular petechiae Vitamin C cause of 1) inadequate nutrient intake caused by anorexia Dermatitis Zinc, vitamin A, niacin, riboflavin, essential fatty and possibly gastrointestinal tract dysfunction, and 2) meta- acids bolic abnormalities caused by alterations in regulatory hor- Bruising, purpura Vitamins C and K mones and cytokines . Alterations in metabolism cause Hair Easily plucked, alopecia Protein, zinc, biotin greater loss of muscle tissue than that observed with pure Corkscrew hairs, coiled Vitamins A and C hair starvation or semi-starvation . Restoration of muscle mass is Eyes Night blindness, kerato- Vitamin A unlikely with nutrition support unless the underlying inflam- malacia, photophobia matory disease is corrected . Most of the weight that is Conjunctival inflamma- Vitamin A and riboflavin gained after providing nutrition support is due to increases tion in fat mass and body water without significant increases in Mouth Glossitis Riboflavin, niacin, folate, vitamin B 12 lean tissue. Bleeding or receding Vitamins A, C, and K; fo- gums, mouth ulcers late Burning or sore mouth/ Vitamins B 12 and C ; folate, Protein-Energy Malnutrition in Children tongue niacin Angular stomatitis or Riboflavin, niacin, pyri- Undernutrition in children differs from that in adults because cheilosis doxin, iron Tetany Calcium, magnesium it affects growth and development. Much of our understand- Neurologic Paresthesias Thiamine, pyridoxine ing of undernutrition in children comes from observations Loss of reflexes, wrist Vitamins B 12 and E made in underdeveloped nations where poverty, inadequate drop, foot drop, loss food supply, and unsanitary conditions lead to a high preva- of vibratory and position sense lence of PEM. The Waterlow classification of malnutrition Dementia, disorienta- Niacin, vitamin B 12 takes into account a child's weight-for-height (wasting) and tion height-for-age (stunting)" (Table 15-12) . The characteristics Ophthalmoplegia Thiamine of the three major clinical syndromes of PEM in children, kwashiorkor, marasmus, and nutritional dwarfism, are outlined in Table 15-13.42 Although these three syndromes are classified separately, they may coexist in the same patient . cal and physical abnormalities but may not cure the underlying cause of the problem. For example, iron therapy corrects iron deficiency anemia but not the factors responsible for the Marasmus deficiency (e.g., inadequate intake, malabsorption, or iron loss). Weight loss and marked depletion of subcutaneous fat and muscle mass are characteristic features of children with marasmus . Loss of fat and muscle make ribs, joints, and facial Protein-Energy Malnutrition bones prominent . The skin is thin, loose, and lies in folds . The term protein-energy malnutrition (PEM) has been used to describe several nutritional deficiency syndromes, includ- Kwashiorkor ing kwashiorkor, marasmus, and nutritional dwarfism in children, and wasting associated with illness or injury in chil- The word "kwashiorkor" comes from the Ga language of dren and adults . Primary PEM is caused by inadequate West Africa and can be translated as "disease of the dis- nutrient intake, so the functional and structural abnormalities placed child" because it was commonly seen after weaning. associated with primary PEM are often reversible with nutri- The presence of peripheral edema distinguishes children with

Table 15-12 1 Waterlow Classification of Protein-Energy Malnutrition in Children

PARAMETER NORMAL

Weight-for-height (wasting) Percent of median NCHS standard 90-110 80-89 70-79 <70 Standard deviation from the NCHS median +Z to -Z -1 .1 Z to -2 Z -2 .1 Z to -3 Z <-3 Z Height-for-age (stunting) Percent of median NCHS standard 95-105 90-94 85-89 <85 Standard deviation from the NCHS median +Z to -Z -1 .1 Z to -2 Z -2 .1 Z to -3 Z <-3 Z

NCHS, National Center for Health Statistics . THE MAI Nt I RIi A- EO P, T,rr T : Nu rRmoNA A$Sts E r

Table 15-13 1 Features of Protein-Energy Malnutrition volume depletion because of inadequate water and sodium Syndromes in Children intake, decreased plasma proteins, "leaky" capillaries, and "leaky" cells . However, the percent of body weight that is NUTRI- composed of water may be increased because of increased TIONAL interstitial ion content and expansion of interstitial space. PARAMETER KWASHIORKOR MARASMUS DWARFISM Therefore, malnourished patients may have diminished intra- Weight for age 60-80 <60 <60 vascular volume in the presence of whole-body fluid over- (% expected) load. Weight for Normal or Markedly Normal height decreased decreased Edema Present Absent Absent Gastrointestinal Tract Mood Irritable when Alert Alert picked up, apathetic Starvation and malnutrition cause structural and functional when alone deterioration of the intestinal tract, pancreas, and liver . The Appetite Poor Good Good total mass and protein content of the intestinal mucosa and pancreas are markedly reduced . Mucosal epithelial cell proliferation rates decrease and the intestinal mucosa becomes kwashiorkor from those with marasmus and nutritional dwarf- atrophic with flattened villi . The synthesis of mucosal and ism. Children with kwashiorkor also have typical skin and pancreatic digestive enzyme is reduced . Intestinal transport hair changes (see sections on hair and skin changes below) . and absorption of free amino acids are impaired, whereas The abdomen is protuberant because of weakened abdominal hydrolysis and absorption of peptides are maintained . The muscles, intestinal distension and hepatomegaly, but there is abdomen may become protuberant because of hypomotility and gas distension. never ascites . In fact, the presence of ascites should prompt the clinician to search for liver disease or peritonitis . Chil- dren with kwashiorkor are typically lethargic and apathetic Skin when left alone but become very irritable when held . Kwashiorkor is not caused by a relative deficiency in protein The skin regenerates rapidly and it takes only 2 weeks for a intake and, in fact, protein and energy intake are similar in basal cell of the dermis to reach the cornified layer and die . children with kwashiorkor and marasmus . Kwashiorkor oc- Undernutrition often causes dry, thin, and wrinkled skin with curs when there is physiologic stress, such as an infection, atrophy of the basal layers of the epidermis and hyperkerato- in an already malnourished child. This explains why kwashi- sis. Severe malnutrition may cause considerable depletion of orkor is an acute illness compared with the chronicity of skin protein and collagen . Patients with kwashiorkor experi- undernutrition alone and why there is overlap between ma- ence sequential skin changes in different locations . Hyper- rasmus and kwashiorkor. Kwashiorkor is characterized by pigmentation occurs first, followed by cracking and stripping leaky cell membranes, which permit the movement of potas- of superficial layers, thereby leaving behind hypopigmented, sium and other intracellular ions into the extracellular space . thin, and atrophic epidermis that is friable and easily macer- The increased osmotic load in the interstitium causes water ated. movement and edema. Hair Nutritional Dwarfism Scalp hair becomes thin, sparse, and is easily pulled out. In The child with failure to thrive may be of normal weight for contrast, the eyelashes become long and luxuriant and there height but has short stature and delayed sexual development . may be excessive lanugo hair in children. Children with Providing appropriate feeding can stimulate catch-up growth kwashiorkor experience hypopigmentation with reddish- and sexual maturation . brown, gray, or blond discoloration . Adults may lose axillary The diagnosis of PEM is different in adults than in chil- and pubic hair . dren because adults do not grow in height. Therefore, undernutrition in adults causes wasting rather than stunting . In Heart addition, although kwashiorkor and marasmus can occur in adults, most studies of adult PEM evaluated hospitalized Chronic undernutrition affects cardiac mass and function. patients who had secondary PEM and coexisting illness or Cardiac muscle mass decreases and is accompanied by frag- injury. mentation of myofibrils . Bradycardia (heart rate can decrease to less than 40 beats/min) and decreased stroke volume can Effect of Protein-Energy Malnutrition on cause a marked decrease in cardiac output and low blood pressure. Tissue Mass and Function

Body Composition Lungs

Although all body tissue masses are affected by undemutri- Respiratory muscle function is altered by malnutrition, as tion, the greatest depletion occurs in fat and muscle masses . evidenced by a decrease in vital capacity, tidal volume, and Many patients who are malnourished also have intravascular minute ventilation. Kidneys History

Renal mass and function are often well preserved during The patient or appropriate family members should be inter- undernutrition, provided adequate water is consumed to pre- viewed to provide insight into the patient's current nutri- vent a severe decrease in renal perfusion and acute renal tional state and future ability to consume an adequate failure. However, when malnutrition is severe, there is a amount of nutrients . The nutritional history should evaluate decrease in kidney weight, glomerular filtration rate, the the following issues: ability to excrete acid, the ability to excrete sodium, and to concentrate urine. Mild proteinuria may also occur . 1. Body weight. Has the patient had mild (<5%), moderate (5%-10%), or severe (>10%) unintentional body weight loss in the last 6 months? In general, a 10% or greater Bone Marrow unintentional loss in body weight in the previous 6 months is associated with a poor clinical outcome .43, a4 Severe undernutrition suppresses bone marrow red blood cell However, it may be difficult to determine true weight and white blood cell production, leading to anemia, leuko- loss. Morgan and coworkers45 showed that the accuracy penia, and lymphocytopenia. of determining weight loss by history was only 0 .67 and the predictive power was 0 .75; hence 33% of patients Muscle with weight loss would be missed, and 25% of those who have been weight-stable would have a diagnosis of weight loss Muscle function is impaired by malnutrition because of both . Furthermore, the nutritional significance of changes in body weight can be confounded by changes in a loss of muscle mass and impaired metabolism . Decreased hydration. sodium pump activity causes an increase in intracellular so- 2. Food intake dium and a decrease in intracellular potassium, which affects . Has there been a change in habitual diet pattern (number, size, and contents of meals)? What is myocyte electrical potential and contributes to fatigue . the reason for altered food intake (e.g., appetite, mental status or mood, ability to prepare meals, ability to chew Immune System or swallow, gastrointestinal symptoms)? 3. Evidence of malabsorption. Does the patient have symp- Severe undernutrition causes atrophy of all lymphoid tissues, toms that are consistent with malabsorption? including thymus, tonsils, and lymph nodes . Cell-mediated 4. Evidence of specific nutrient deficiencies . Are there immunity is diminished more than antibody production . Al- symptoms of specific nutrient deficiencies, including ma- terations in cell-mediated immunity cause impaired delayed crominerals, micronutrients, and water (see Tables 15-8 cutaneous hypersensitivity and anergy . The ability to kill to 15-11)? bacteria is diminished because of decreased complement and 5. Influence of disease on nutrient requirements . Does the impaired neutrophil function . Gastrointestinal IgA secretion patient's underlying illness increase nutrient needs be- is also decreased. Malnourished patients are at increased risk cause of high metabolic stress or nutrient losses? for opportunistic infections and should be considered immu- 6. Functional status . Has the patient's ability to function and nocompromised . perform normal daily activities changed?

Brain Physical Examination

The weight and protein content of the brain remain relatively The physical examination corroborates and adds to the find- stable during prolonged malnutrition . Therefore, the integrity ings obtained by history . of the brain is preserved at the expense of other organs and tissues . 1 . Body mass index (BMI), which is defined as weight (in kilograms) divided by height (in square meters), can help identify patients at increased risk of an adverse clinical Nutritional Assessment Techniques outcome46, 47 (Table 15-14) . Patients who are extremely underweight (BMI < 14 kg/m 2) are at high risk of death The current methods that are used clinically to evaluate and should be considered for admission to the hospital PEM in hospitalized adult patients shifts nutritional assess- for nutrition support. ment from a diagnostic to a prognostic instrument in an 2. Anthropometry . Triceps and subscapular skinfold thick- attempt to identify patients who can benefit from nutritional nesses provide an index of body fat ; midarm muscle therapy . The commonly used indicators of the degree of circumference provides a measure of muscle mass . Al- protein-energy malnutrition, detailed below, correlate with though these measurements seem to be useful in popula- clinical outcome . However, these indicators are always influ- tion studies, their reliability in individual patients is less enced by illness or injury, making it difficult to distinguish clear. The most commonly used standards for triceps the contribution of malnutrition from the severity of illness skinfold thickness and midarm muscle circumference are itself on outcome . Specific features of the medical history, those reported by Jelliffe, 48 which are based on measure- physical examination, and laboratory tests that emphasize the ments of European male military personnel and low-in- indicators which assess generalized nutritional status include come American women, and those reported by Frisan- the following points . cho,49 which are based on measurements of white males

i -IE AQA!AC>Lf'tSl4EL) PA)7J'T : Nt'rRl15)1

Table 15-14 1 Classification of Nutritional Status SERUM ALBUMIN . Several studies have demonstrated that a by Body Mass Index in Adults low serum albumin concentration is correlated with an increased incidence of medical complications . s3-55 However, BODY MASS INDEX an understanding of albumin physiology clarifies why serum (kg/m=) NUTRITIONAL STATUS albumin concentration is correlated with disease severity in <16 .0 Severely malnourished hospitalized patients, but may be inappropriate as a measure 16.0-16.9 Moderately malnourished of nutritional status per se.56 Albumin is highly water-soluble 17 .0-18 .4 Mildly malnourished and resides in the extracellular space . The total body pool of 18.5-24 .9 Normal albumin in a normal 70-kg man is approximately 300 g . 25.0-29.9 Overweight 30 .0-34 .9 Obese (class I) Approximately one third of the total pool constitutes the 35 .0-39.9 Obese (class II) intravascular compartment, and two thirds constitute the ex- ?40 Obese (class III) travascular compartment.57 The concentration of albumin in blood is greater than that in lymph or other extracellular fluids, but the ratio of intravascular to extravascular albumin concentration varies from tissue to tissue . Within 30 minutes and females participating in the 1971 to 1974 United of initiating albumin synthesis, the hepatocyte secretes albu- States Health and Nutrition Survey . The use of these min into the bloodstream .5 S Once albumin is released into standards to identify malnutrition in many patients is plasma, its half-life is approximately 20 days . During steady problematic because of the restricted database and the state conditions, approximately 14 g of albumin (200 mg/kg) absence of correction factors for age, hydration, and are produced and degraded daily . Thus, approximately 5% physical activity on anthropometric parameters . Several of the total albumin pool is degraded and replaced by newly studies have demonstrated that 20% to 30% of healthy synthesized albumin every day . Equilibration of albumin in control subjects would be considered malnourished on the the intravascular compartment is rapid and occurs within basis of these standards and that there is poor correlation minutes after albumin enters the bloodstream . Equilibration between Jelliffe's and Frisancho's standards in classifying between intravascular and extravascular albumin is slower. patients .50 51 Furthermore, Hall and associates 52 found Every hour approximately 5% of the plasma albumin pool considerable inconsistencies when anthropometric mea- exchanges with extravascular albumin, so that the total surements were performed by different observers . plasma albumin mass exchanges with extravascular albumin 3. Hydration status. The patient should be evaluated for each day . signs of dehydration (manifested by hypotension, tachy- Protein-calorie malnutrition (i.e., the state of prolonged cardia, postural changes, mucosal xerosis, decreased axil- deficient intake of protein and calories) causes a decrease in lary sweat, and dry skin), and excess body fluid (mani- the rate of albumin synthesis . Within 24 hours of fasting, the fested by edema or ascites) . rate of albumin synthesis decreases markedly .59 However, a 4. Tissue depletion. A general loss of adipose tissue can be short-term reduction in albumin synthesis has little impact judged by clearly defined bony, muscular, and venous on albumin levels because of albumin's slow turnover rate outlines and loose skinfolds . A fold of skin, pinched and large pool size . Indeed, plasma albumin concentration between the forefinger and thumb, can reveal the ade- may actually increase during short-term fasting because of quacy of subcutaneous fat . The presence of hollowness in reduction of intravascular water .60 Even during chronic mal- the cheeks, buttocks, and perianal area suggests body fat nutrition, plasma albumin concentration is often maintained loss. An examination of the temporalis, deltoid, and because of a compensatory decrease in albumin degradation quadriceps muscles should be made to search for muscle and a transfer of extravascular albumin to the intravascular wasting. compartment. Prolonged protein-calorie restriction induced 5. Muscle function . Strength testing of individual muscle experimentally in human volunteers 31 or observed clinically groups should be made to evaluate for generalized and in patients with anorexia nervosa 61 causes marked reductions localized muscle weakness . In addition, a general evalua- in body weight but little change in plasma albumin concen- tion of respiratory and cardiac muscle function should be tration . A protein-deficient diet with adequate calories in made. elderly persons causes a decrease in lean body mass and 6. Specific nutrient deficiencies (see Tables 15-8 to 15- muscle function without a change in plasma albumin con- 11). Rapidly proliferating tissues, such as oral mucosa, centration .62 hair, skin, and bone marrow are often more sensitive to Hospitalized patients may have low levels of plasma al- nutrient deficiencies than are tissues that turn over more bumin for several reasons . Inflammatory disorders cause a slowly . decrease in albumin synthesis,63 an increase in albumin degradation,64 and an increase in albumin transcapillary losses .65 Specific gastrointestinal and cardiac diseases increase albu- Laboratory Tests min losses through the gut, whereas some renal diseases can cause considerable albuminuria . Wounds, burns, and perito- Specific Nutrient Deficiencies nitis can cause albumin losses from the injured surface or damaged tissues. During serious illness, vascular permeabil- Suspected specific nutrient deficiencies based on history and ity increases dramatically and alters albumin exchange be- physical examination can be further corroborated by appro- tween intravascular and extravascular compartments . Albu- priate diagnostic laboratory tests (see Tables 15-8 to min losses from plasma to the extravascular space were 15-11) . increased twofold in patients with cancer-related cachexia

l ' ttOENTEROL '~rcY

and threefold in patients with septic shock . Plasma albumin provided a quantitative estimate of postoperative complica- levels do not increase in stressed patients until the inflamma- tions when applied prospectively to patients undergoing gas- tory stress remits . For example, albumin levels fail to in- trointestinal surgery . crease in patients with cancer after 21 days of intensive nutritional therapy .66 Subjective Global Assessment SERUM PREALBUMIN . Prealbumin is a transport protein for thyroid hormones and exists in the circulation as a retinol- A clinical method for evaluating nutritional status, termed binding prealbumin complex . The turnover rate of this pro- the subjective global assessment, encompasses historical, . 76 tein is rapid, with a half-life of 2 to 3 days . It is synthesized symptomatic, and physical parameters (Table 15-15) .75 by the liver and is catabolized partly by the kidneys . Pro- This approach defines malnourished patients as those who tein-energy malnutrition reduces the levels of prealbumin, are at increased risk for medical complications . The purpose and refeeding restores levels . 67 However, prealbumin levels of this assessment is to determine whether nutrient assimila- decrease without malnutrition in patients with infections 68 tion has been restricted because of decreased food intake, and in response to cytokine 69 and stress hormone infusion .70 maldigestion, or malabsorption; whether weight loss has oc- Renal failure increases levels," whereas liver failure may curred ; whether weight loss in the previous 6 months was cause a decrease in levels . The influence of disease-related mild (<5%), moderate (5% to 10%), or severe (>10%) ; the factors on prealbumin concentration makes it unreliable as pattern of weight loss (e .g ., a patient who had recently an index of nutritional status in hospitalized patients . regained weight would not be considered malnourished) ; whether any effects of malnutrition on organ function and CREATININE-HEIGHT INDEX . The amount of creatinine ex- body composition are present ; and whether the patient's dis- creted in urine provides a measure of skeletal muscle and ease process influences nutrient requirements (e .g ., high- lean body masses . 72 Approximately 2% of creatine, which is stress conditions are burns, major trauma, and severe inflam- distributed mainly in muscle cells, is converted daily by an mation, whereas moderate-stress diseases are mild infections irreversible nonenzymatic reaction to creatinine, which is and limited malignant tumor) . subsequently excreted unchanged in urine . The creatinine- The findings of the history and physical examination are height index is determined by measuring 24-hour urinary used to categorize patients as well nourished (category A), creatinine excretion in relationship to the patient's height having mild or moderate malnutrition (category B), or hav- while the patient is consuming a creatine and creatinine-free ing severe malnutrition (category C) . The rank is assigned diet . However, the normal range of values was derived from on the basis of subjective weighting ; equivocal information healthy men and women of ideal body weight . Estimates of is given less weight than definitive data . Fluid shifts related "ideal" muscle mass may not apply to patients whose to onset or treatment of edema or ascites must be considered weights do not fall within the ideal range . Furthermore, the in interpreting changes in body weight. In general, a patient validity of the creatinine-height index can be affected by who has experienced weight loss and muscle wasting but is inaccurate urine collections, alterations in protein intake, and currently eating well and gaining weight is classified as well medical variables that alter creatinine excretion, independent nourished . A patient who has experienced moderate weight of muscle mass (e .g ., renal failure, sepsis, trauma, exercise, loss, continued compromised food intake, continued weight and steroid therapy) . loss, progressive functional impairment, and a moderate- stress illness is classified as moderately malnourished. A patient who has experienced severe weight loss and contin- Immune Competence ues to have poor nutrient intake, progressive functional impairment, and muscle wasting is classified as severely mal- Immune competence, as measured by delayed cutaneous hy- nourished, independent of disease stress . Several studies persensitivity (DCH), is altered by severe malnutrition and have found that the use of subjective global assessment in patients suffering from severe PEM can become anergic . evaluating hospitalized patients gives reproducible results However, a large number of clinical factors also influence and that there was more than 80% agreement when two DCH, making it a poor marker of malnutrition in sick pa- blinded observers assessed the same patient76.77 Detsky and tients . The following factors alter DCH in the absence of colleagues 77 found that preoperative subjective global assess- malnutrition : 1) infection ; 2) illnesses, such as uremia, cir- ment was a better predictor of postoperative infectious com- rhosis, hepatitis, myocardial infarction, trauma, burns, and plications than were serum albumin concentration, DCH, an- hemorrhage ; 3) medications, such as steroids, immunosup- thropometry, creatinine-height index, and the prognostic pressants, cimetidine, and warfarin ; and 4) medical proce- nutritional index . dures, such as anesthesia and surgery .

Muscle Function Discriminant Analysis Impaired muscle function is a manifestation of malnutrition Discriminant function analysis, based on retrospective evalu- and often occurs before there are structural alterations in ation of multiple parameters, has been used to develop pre- muscle mass . Although muscle function testing is not rou- .71, 74 dictive equations of clinical outcome Serum protein tinely used in nutritional assessment, it may gain greater concentrations and DCH are important variables included in acceptance with experience . Electrical stimulation of the ul- these equations . Buzby and colleagues 73 found that their pre- nar nerve at the wrist permits the measurement of several dictive equation, termed the prognostic nutritional index, involuntary muscle function parameters of the adductor pol- THE MAL . )I ;RI HEf) P:Al1E',[ : NUTRITIONAL As sSMEtrI'

Table 15-15 1 Features of Subjective Global Assessment (SGA)

HISTORY Weight Change Loss in past 6 months : amount = kg; % loss = Change in past 2 weeks : Increase No change Decrease . Dietary Intake Change: No change Change Duration = weeks Type : Suboptimal solid diet Hypocaloric liquids Starvation Gastrointestinal Symptoms (That Persisted for > 2 Weeks) : None Nausea Vomiting Diarrhea Anorexia Functional Capacity No dysfunction Dysfunction Duration = weeks Type Working suboptimally Ambulatory but not working Bedridden Effect of Disease on Nutritional Requirements Primary diagnosis : Metabolic Demand : Low stress Moderate stress High stress PHYSICAL EXAMINATION (NORMAL, MODERATE, OR SEVERE) Loss of subcutaneous fat (triceps, chest) Muscle wasting (quadriceps, deltoids) Ankle or sacral edema Ascites SGA RATING A = Well nourished B = Mild or moderate malnutrition C = Severe malnutrition

licis muscle . Studies performed during starvation and refeed- medical complications, it is not clear whether the restoration ing in humans suggest that muscle function testing can pro- of function leads to an improvement in clinical outcome . vide a sensitive measure of the adequacy of nutrient The authors recommend that nutritional assessment involve a intake."-80 Short-term parenteral nutritional therapy has also careful nutritional history and physical examination . In addi- been shown to improve respiratory and hand muscle function tion, appropriate laboratory studies should be obtained as in malnourished patients with inflammatory bowel disease 81 needed to further evaluate considerations raised during the and malnourished patients awaiting surgery .8'2 Moreover, clinical examination . The information from this evaluation muscle function may be a better predictor of clinical out- should help determine the patient's current clinical condition come than other markers of nutritional status, such as arm and the anticipated duration of inadequate volitional feeding muscle circumference, serum albumin concentration, and to identify patients who may require oral, enteral, or paren- weight loss .83-85 teral nutrition support (see Chapter 16, Enteral and Paren- teral Nutrition) .

Overview of Nutritional Assessment REFEEDING THE MALNOURISHED At present, there is no gold standard for evaluating nutri- PATIENT tional status, and the reliability of any nutritional assessment technique as a true measure of nutritional status has never Refeeding the severely malnourished patient is necessary to been validated . No prospective randomized controlled clini- reverse the adverse effects of malnutrition and to prevent cal trials have been performed to evaluate whether providing death from starvation . The goal is to inhibit mobilization of nutrition support improves clinical outcome in patients endogenous fuels and use ingested or infused nutrients to judged to be severely malnourished compared with those meet body nutritional requirements and rebuild lost nutrient who are judged to be mildly or moderately malnourished . stores . However, a retrospective subgroup analysis of a large multi- center trial found that parenteral nutrition given preopera- tively to patients with a diagnosis of severe malnutrition by Refeeding Syndrome subjective global assessment or a nutritional risk index (based on serum albumin and body weight change) de- Because of the structural, functional, and metabolic altera- creased postoperative infectious complications .86 The poten- tions caused by previously inadequate food intake, injudi- tial use of muscle function as a measure of nutritional status cious nutritional therapy can have adverse clinical conse- represents an exciting area for further investigation . Al- quences known in part as the refeeding syndrome .", "I Early though there is strong evidence that muscle function pro- evidence of the refeeding syndrome was reported at the end vides an index of both nutritional state and the risk of of World War II, when it was found that oral refeeding of chronically semistarved research volunteers and war victims parenteral glucose may not be well tolerated initially and caused cardiac insufficiency and neurologic complications ." may produce marked elevations in blood glucose, glucosuria, More recently, refeeding abnormalities and serious complica- dehydration, and hyperosmolar coma. 102 Furthermore, be- tions have been reported after aggressive refeeding in hospi- cause of the importance of thiamine in glucose metabolism, talized cachectic patients .90, 91 carbohydrate refeeding in patients who have thiamine depletion can precipitate Wernicke's encephalopathy .l°3

Fluid Overload Gastrointestinal Dysfunction Decreased cardiac mass, stroke volume, and end-diastolic volume ; bradycardia ; and fragmentation of cardiac myofibrils Starvation and malnutrition cause structural and functional are associated with chronic undernutrition .92-95 In addition, deterioration of the GI tract. The total mass and protein carbohydrate refeeding increases the concentration of circu- content of the intestinal mucosa and pancreas are markedly lating insulin, which enhances sodium and water reabsorp- reduced . Mucosal epithelial cell proliferation rates, the syn- tion by the renal tubule .96 These factors put the severely thesis of mucosal and pancreatic digestive enzymes, and malnourished patient at increased risk of fluid retention and intestinal transport and absorption of free amino acids are congestive heart failure after nutritional therapy containing impaired,104 whereas hydrolysis and absorption of peptides water, glucose, and sodium . are better maintained. 105 These alterations limit the ability of the GI tract to digest and absorb food. When malnutrition is severe, oral refeeding has been associated with increased Mineral Depletion incidence of diarrhea and death . 106 However, most of the adverse consequences of starvation on the GI tract disappear Of the mineral abnormalities associated with refeeding, after 1 to 2 weeks of refeeding . phosphate depletion has received the most attention . During starvation, phosphorus requirements are decreased because of the predominant use of fat as a fuel source . Serum phos- Cardiac Arrhythmias phate is maintained at normal levels by mobilizing bone stores and increasing renal tubular reabsorption . Refeeding Ventricular tachyarrhythmias, which can be fatal, occur dur- with enteral carbohydrates or glucose-based parenteral for- ing the first week of refeeding . 107 A prolonged QT interval, mulas stimulates insulin release and intracellular uptake of often documented before death, is a contributing cause of phosphate .97 Phosphate is needed for protein synthesis and the rhythm disturbances . It is not known whether refeeding for the production of phosphorylated intermediates necessary per se or the cardiac dysfunction underlying malnutrition for glucose metabolism .98 These metabolic processes can precipitated the terminal arrhythmias . cause extracellular phosphorus concentration to fall below 1 mg/dL within hours of initiating nutritional therapy if adequate phosphate is not given . Severe hypophosphatemia, Clinical Recommendations which is associated with muscle weakness, paresthesias, seizures, coma, cardiopulmonary decompensation, and death, Initial Evaluation has occurred in patients receiving enteral or parenteral nutritional repletion.9°. 91, 99. 100 However, it is difficult to deter- The severity of complications during refeeding cachectic, mine the contribution of hypophosphatemia to the reported chronically semistarved patients emphasizes the importance clinical complications because of other coexistent medical of a particularly cautious approach to their nutritional ther- and nutritional abnormalities . apy, particularly during the first week of therapy when the Potassium and magnesium are the most abundant intracel- risk of complications is highest . A careful search for cardio- lular cations . Loss of body cell mass in the malnourished vascular and electrolyte abnormalities should be performed patient causes whole body potassium and magnesium deple- before refeeding . In addition, a search for infections (e.g., tion. Serum potassium and magnesium concentrations, how- obtaining a white blood cell count, urine analysis and cul- ever, remain normal or near normal during starvation be- ture, blood cultures, and chest radiograph) should be consid- cause of their release from tissue and bone stores . The ered even in the absence of physical findings, because many increases in protein synthesis rates, body cell mass, and patients are not able to mount a normal inflammatory re- glycogen stores during refeeding require increased intracellu- sponse. lar potassium and magnesium . In addition, hyperinsulinemia during refeeding increases cellular uptake of potassium and can cause a rapid decline in extracellular concentrations .'°' Initial Supportive Care Judicious resuscitation with fluids and electrolytes may be Glucose Intolerance necessary before beginning feedings to prevent congestive heart failure from excessive fluid . Vitamin supplementation The adaptive changes during starvation enhance use of fatty should be given routinely . Severely malnourished patients acids and ketone bodies for fuel while glucose is conserved . are poikilothermic so warm ambient temperature and warm- In addition, the ability of insulin to stimulate glucose uptake ing blankets may be necessary to slowly increase core tem- and oxidation by peripheral tissues is impaired . 101 Thus, re- perature. However, if warming blankets are being used, pa- feeding with high-carbohydrate meals or large amounts of tients must be carefully monitored to avoid hyperthermia. THE MALNOURISHED PATIENT : NUTRITIONAL ASSESSMtNT AND eIVAANY

Feeding Regimen approach depends on the functioning of the intestinal tract ; the presence of macronutrient, micronutrient, electrolyte, and Patients can be refed orally, by enteral tube feeding, by fluid deficits ; identification of risk factors for future medical parenteral nutrition, or through a combination of these meth- complications; the presence of coexisting diseases that ham- ods. Oral or enteral tube feedings are preferred over paren- per the ability to provide nutritional therapy; and an evalua- teral feeding because of fewer serious complications and tion of factors that affect the patient's daily activities . enhanced gastrointestinal tract recovery . Isotonic feedings A careful review of medical records, operative reports, should be given in small amounts at frequent intervals to and radiologic studies is needed to evaluate the absorptive prevent overwhelming the body's limited capacity for nutri- capacity of the intestine by determining the length of re- ent processing and to prevent hypoglycemia, which can oc- maining intestine, the site of intestinal disease or resection, cur during brief nonfeeding intervals . Parenteral supplemen- and the presence of diseases that reduce intestinal absorp- tation or complete parenteral nutrition may be necessary if tion, such as pancreatic insufficiency or cholestasis . An as- the intestine cannot tolerate oral/enteral feeding . A combina- sessment of fluid losses through diarrhea, ostomy output, and tion of many nutrients, particularly nitrogen, phosphorus, fistula volume should be made to help determine fluid re- potassium, magnesium, and sodium, is needed to restore lean quirements . Knowledge of fluid losses is also useful in cal- body mass . Inadequate intake of one nutrient may impair culating intestinal mineral losses by multiplying fluid loss by retention of others during refeeding . the estimated electrolyte concentration in intestinal fluid Although it is impossible to know the precise nutrient (Table 15-16) . In patients who do not respond to treatment requirements of individual patients, some general guidelines as predicted, dynamic studies of intestinal absorptive func- are recommended for the first week of refeeding . Fluid in- tion may be helpful in adjusting the treatment program . Such take should be limited to approximately 800 mL/day plus studies include measuring fat, carbohydrate, and nitrogen replacement for insensible losses . Adjustments in fluid intake balance and evaluating ostomy, fecal, or fistula mineral and are necessary in patients who have evidence of fluid over- fluid losses . load or dehydration. Changes in body weight provide a use- The urgency for medical intervention is determined by ful guide for evaluating the efficacy of fluid administration . the severity of hemodynamic and nutritional abnormalities. Weight gain greater than 0 .25 kg/day, or 1 .5 kg/week, prob- This requires an evaluation for volume depletion, weight ably represents fluid accumulation . Daily calorie intake loss, and specific nutrient deficiencies . In addition to stan- should be approximately 15 to 20 kcal/kg, containing ap- dard laboratory tests to evaluate for anemia (iron, folate, or proximately 100 g of carbohydrate and 1 .5 g of protein per vitamin B 12 deficiency), prolonged prothrombin time (vita- kilogram body weight. Sodium should be restricted to ap- min K deficiency), and electrolyte abnormalities, more so- proximately 60 mEq or 1 .5 g/day, but liberal amounts of phisticated measurements to determine vitamin and trace phosphorus, potassium, and magnesium should be given to mineral status can be obtained when deficiencies are sus- patients who have normal renal function tests results . All pected clinically. Bone mineral densitometry may be useful other nutrients should be given in amounts needed to meet in many patients to establish a baseline and to screen for the recommended dietary allowance . Daily monitoring of unrecognized bone mineral depletion . An accurate dietary body weight, fluid intake, urine output, and plasma glucose history obtained by using food records is useful in evaluat- and electrolyte values are critical during early refeeding (first ing nutrient requirements in nutritionally stable patients and 3-7 days), so that nutritional therapy can be appropriately in identifying dietary inadequacies in those with nutrient adjusted when necessary . deficiencies. Finally, it is also important to consider specific problems that interfere with the patient's quality of life . Maintaining PATIENTS WITH SEVERE adequate nutritional status with oral feedings at the cost of MALABSORPTION massive diarrhea and frequent bowel movements may be unacceptable to the patient with an active social or profes- Some patients become malnourished because of impaired sional life outside the home . In this patient, parenteral sup- gastrointestinal tract absorptive capacity . These patients have plementation may be necessary to improve the quality of inadequate functional small bowel length because of intesti- life. nal resection or intestinal disease and present the most chal- lenging nutritional management problems for the clinician . The medical management of these patients is often difficult Table 15-16 1 Electrolyte Concentrations and frustrating, but it can be made much easier by under- in Gastrointestinal Fluids* standing the physiologic and clinical principles of treatment . Malabsorption syndromes and short bowel syndrome are dis- Na K CI HCO 3 LOCATION (mEq/L) (mEq/L) (mEq/L) (mEq/L) cussed in greater detail in Chapters 89 and 92, respectively . Stomach 65 10 100 Bile 150 4 100 35 Clinical Considerations Pancreas 150 7 80 75 Duodenum 90 15 90 15 The initial assessment of the patient with chronic malabsorp- Mid-small bowel 140 6 100 20 Terminal ileum 140 8 60 70 tion is meant to provide a logical basis for developing a Rectum 40 90 15 30 treatment strategy to improve the patient's current clinical condition and prevent future complications . The therapeutic *Average values are listed ; these can vary considerably from patient to patient . Treatment However, these capsules are not commercially available and require a willing pharmacist to make them . Diphenoxylate The goals of therapy are to control diarrhea ; maintain fluid, with atropine (Lomotil) is an effective agent, but it is expen electrolyte, and nutritional homeostasis ; treat and prevent sive and inconvenient if large doses are needed . medical complications ; and maximize the quality of life . The Foods and medications that cause diarrhea should be therapeutic approach depends on the results of the clinical avoided . Traditionally, the recommendation has been to de- evaluation . Initial therapy often requires subsequent modifi- crease or eliminate lactose-containing foods because of the cation using a trial-and-error approach, because of individual reduction in intestinal lactase in patients who have had intes- variability in absorptive function, continued intestinal adapta- tinal resection . However, patients with jejunostomies with 15 tion, and the development of new medical complications or to 150 cm of jejunum remaining can tolerate 20-g lactose disease progression . Continued clinical monitoring is critical loads as milk or yogurt ."s Although lactose was better ab- so that medical and nutritional therapy can be adjusted when sorbed from yogurt than from milk, there was no difference necessary . in clinical symptoms . Foods that have laxative effects, such as caffeine-containing drinks and diet products containing osmotically active sweeteners (sorbitol, xylitol, and manni- Control of Diarrhea tol), should be avoided . Medications that contain magnesium or sorbitol can also contribute to diarrhea . 110 Diarrhea is often caused by a combination of factors, including increased gastrointestinal secretions, decreased intestinal Enteral Feeding transit time, and osmotic stimulation of water secretion by unabsorbed luminal contents . Therefore, therapy for diarrhea The ability to use the gut to provide nutritional therapy involves limiting endogenous secretions, slowing motility, depends on intestinal absorptive function as well as on the and improving solute absorption . patient's ability to feed without producing adverse symp- The stomach normally produces approximately 2 .5 L of toms . Patients with nausea, vomiting, abdominal pain, or fluid per day, which is absorbed by the small bowel . Gastric severe diarrhea may be unable to tolerate enteral feeding secretion and, in some patients, gastric hypersecretion may regardless of intestinal absorptive capacity . Specific foods contribute to diarrhea . The use of Hz receptor antagonists or that cause gastrointestinal complaints should be avoided . proton pump inhibitors may be necessary to reduce gastric However, it is important to evaluate objectively the validity secretions . The presence of acidic jejunostomy or ileostomy of these complaints to prevent the unnecessary withdrawal of contents after meals is a clear indication for acid-reduction nutritious foods . Patients with gluten-sensitive enteropathy therapy ."" Large dosages, twice the normal amount used for require a strict gluten-free diet . the treatment of peptic ulcer disease or reflux, may be re- The goal of feeding is to provide the patient with all quired for adequate control in certain patients because of recommended nutritional requirements . The amount of in- reduced drug absorption . gested nutrients needed to reach this goal depends on the The long-acting somatostatin analog, octreotide acetate normal recommended dietary allowances modified by an es- (Sandostatin) can decrease small intestine secretions . Ther- timate of absorptive function and intestinal losses . This usu- apy with octreotide has been shown to decrease ostomy or ally requires ingestion of large amounts of fluid, calories. stool volume (by 500 to 4000 g/day), decrease sodium and protein, vitamins, and minerals . Even in patients with severe chloride output, and prolong small bowel transit time in short bowel syndrome, total parenteral nutrition may not be patients with short bowel syndrome . 109-111 However, octreo- needed when vitamin and mineral supplements and large tide therapy does not improve absorption of macronutrients amounts of calories and protein are provided enterally ."' and other minerals . In addition, octreotide is expensive, must Increasing the time that food is in contact with the intestine be given by subcutaneous injections, can decrease appetite, may enhance absorption in patients with limited absorptive impair fat absorption,' 12 increase the risk of gallstones, 1 ' function . For this reason, total dietary intake should be di- and decrease the use of amino acids for splanchnic protein vided into at least six meals per day . If this is unsuccessful, synthesis .' 14 Nevertheless, in patients who have persistent defined liquid formulas ingested between meals or adminis- large volume intestinal output despite standard antidiarrheal tered by continuous tube feedings at night may prevent the therapy, a trial of 100 µg octreotide injected subcutaneously need for parenteral nutrition . In general, most patients with three times a day with meals may be useful . severe malabsorption must ingest 40 to 60 kcal/kg/day and Opiates are the most effective means for slowing intesti- 1 .2 to 1 .5 g of protein/kg/day . Suggested guidelines for nal motility and act by delaying gastric emptying, decreasing vitamin and mineral supplementation are outlined in Table peristalsis of the small and large intestine, and increasing 15-17 . The needs of each patient, however, can be deter- anal sphincter tone . Loperamide (Imodium) should be tried mined only by experimentation with different dietary manip- first, because it is metabolized on first pass by the liver and ulations . does not easily cross the blood-brain barrier, thereby limiting its side effects and potential for drug dependence . If loper- FAT INTAKE . Fat intake should not be restricted in patients amide is not effective, other opiates, such as codeine or with a jejunostomy or ileostomy despite the presence of deodorized tincture of opium (10 to 25 drops every 6 hours), steatorrhea . A high-fat, low-carbohydrate diet has been should be considered . In addition, the combination of an found to be comparable to a low-fat, high-carbohydrate diet anticholinergic drug and an opiate may be beneficial . We with regard to total fluid, energy, nitrogen, sodium, potas- have found that capsules containing 25 mg powdered opium sium, and divalent ion absorption in patients with short and 15 mg powdered belladonna are a potent combination . bowel syndrome .' 11-120 Furthermore, a high-fat diet facili-

THE MALNOURIM,t t r PAM N3 : Nut RITK?NAt AsSE s 2 , rtNtn

Table 15-17 1 Guidelines for Vitamin and Mineral sorption, but not total calorie absorption, was greater when a Supplementation in Patients with Severe peptide-based diet was consumed than when a diet contain- Malabsorption ing whole proteins was consumed. However, it is not known whether the increase in nitrogen absorption led to an im- SUPPLEMENT provement in protein metabolism or nitrogen balance, (REPRESENTATIVE because these parameters were not measured . Blood urea ni- PRODUCT) DOSE ROUTE trogen and urinary urea excretion were greater during pep- Prenatal multivitamin with 1 tab qd po tide-based diet feeding than during whole protein diet inges- minerals* tion, suggesting that the absorption of additional amino acids Vitamin D* 50,000 U 2-3 times per po stimulated amino acid oxidation . Therefore, at present there week is insufficient clinical evidence to justify the routine use of Calcium* 500 mg elemental cal- po cium tid to qid expensive predigested formulas in patients with short bowel Vitamin B 12t 1 mg qd po syndrome . 100-500 µg q 1-2 mo s.c. Vitamin At 10,000 to 50,000 U qd po ORAL REHYDRATION THERAPY. A subset of patients, usu- Vitamin Kt 5 mg/d po ally those with 50 to 100 cm of jejunum that either ends in (Mephyton; Aqua- 5-10 mg/wk S .C . a jejunostomy or is anastomosed to the midtransverse or MEPHYTON) distal colon, cannot maintain fluid and electrolyte homeosta- Vitamin Et (Aquasol E) 100 U/d po Magnesium gluconatet (Ma- 108-169 mg elemental po sis but may be able to absorb adequate protein and calories . gonate) or magnesium ox- magnesium qid These patients may benefit from oral rehydration therapy ide capsules (URO-MAG) that takes advantage of the sodium-glucose cotransporter Magnesium sulfatet 290 mg elemental mag- IM/IV present in the brush border of intestinal epithelium . 125 Fre- nesium 1-3 times per wk quent ingestion of small volume feedings of an isotonic Zinc gluconate or zinc sul- 25 mg elemental zinc qd po glucose or starch-based electrolyte solution 126 stimulates ac- fatet plus 100 mg elemental tive sodium transport across the intestine, whereas water zinc/L intestinal output follows passively by solvent drag. 127 Data from studies in Ferrous sulfatet 60 mg elemental iron tid po animals and patients with short bowel syndrome suggest that Iron dextrant X100 mg elemental iron IV per day based on for- sodium and water absorption is maximal from solutions con- mula or table taining 90 to 120 mmol/L of sodium .'25 Unfortunately, most commercially available oral rehydra- *Recommended routinely for all patients . tRecommended for patients with documented nutrient deficiency or malab- tion formulas and sport drinks contain lower sodium concen- sorption . trations and are not optimal for patients with short bowel IM, intramuscular ; IV, intravenous ; po, oral ; s.c., subcutaneous . syndrome. However, inexpensive and more effective solutions can be made by patients at home (Table 15-18). Daily oral administration of 1 to 2 L of rehydration solutions has tates the ingestion of more calories . Limiting fat intake, been successful in correcting fluid and electrolyte abnormali- however, may decrease gastrointestinal symptoms, colonic ties and allows intravenous supplementation to be discontin- water secretion, hyperoxaluria, and divalent certain losses in ued in patients who have had extensive intestinal resec- 121, 122 patients who have steatorrhea and an intact colon . tion. 12s-111 In some patients, oral rehydration therapy has Theoretically, medium-chain triglycerides (MCTs) are decreased ostomy output by 4 L/day . 131 useful as a feeding supplement in patients who have impaired fat absorption, because they are rapidly hydrolyzed MAJOR MINERALS . Major minerals should be supplemented and do not require bile salts and micelle formation for ab- as needed, depending on the assessment of body content . sorption . 123 However, many patients do not find MCT oil Maintaining magnesium homeostasis is often difficult, be- palatable. Furthermore, MCT oil can cause nausea, vomiting, cause magnesium is poorly absorbed and enteral supplemen- and abdominal discomfort . A dosage of 1 tablespoon (15 tation with magnesium salts increases diarrhea . Enteric- mL) three to four times daily, providing a total of approxi- coated magnesium supplements should not be used, because intestine for mately 500 kcal, is usually the maximal amount tolerated . their delayed release reduces contact with the absorption .132 PREDIGESTED FORMULAS . Predigested formulas-that is; Soluble magnesium salts, such as magnesium gluconate, monomeric (elemental) and oligomeric formulas-have been are better tolerated and absorbed than are other magnesium recommended for patients with short bowel syndrome . Theo- complexes . In some patients, magnesium is best given in retically, these formulas, which contain nitrogen in the form liquid form as magnesium gluconate (Fleming Inc ., St. of free amino acids or small peptides, are absorbed more Louis, MO) and can be added to a oral rehydration solution efficiently over a shorter length of intestine than are poly- in doses of 18 to 27 mmol (432 to 648 mg of elemental meric formulas or whole food . However, the clinical efficacy magnesium) per day . This solution should be sipped, not of these formulas is not clear. Two prospective trials, using ingested as a bolus, to maximize absorption and avoid diar- a randomized cross-over design, have evaluated the use of rhea. Normal serum magnesium levels do not exclude the predigested formulas in patients with a jejunostomy and less possibility of magnesium deficiency . The percentage of mag- than 150 cm of residual small bowel.120• 124 McIntyre and nesium excreted in urine after infusion may prove to be a colleagues 120 found no difference in nitrogen or total calorie better index of body magnesium stores ; excretion of less absorption between a polymeric and an oligomeric diet. In than 80% of infused magnesium suggests whole body mag- contrast, Cosnes and coworkers 124 found that nitrogen ab- nesium depletion . 133 IN GASTkOENTFR(_11 Q( r

Table 15-18 1 Characteristics of Selected Oral Rehydration Solutions

Equalyte 78m 22 68 1900 mg 100 25 305 CeraLyte 70 70 20 98 30 165 40 235 CeraLyte 90 90 20 98 30 165 40 260 Pedialyte 45 20 35 30 100 20 300 Rehydralyte 74 19 64 30 100 25 305 Gatorade 20 3 N/A N/A 210 45 330 WHO 90 20 80 30 80 20 200 Washington University 105 0 100 10 85 20 250

Equalyte also contains fructooIigosaccharides . WHO (World Health Organization) formula : Mix 3/4 tsp sodium chloride, 1/2 tsp sodium citrate, 1/4 tsp potassium chloride, and 4 tsp glucose (dextrose) in 1 L (4 1/4 cups) of distilled water . Washington University formula : Mix 3/4 tsp sodium chloride, 1/2 tsp sodium citrate, and 3 tbsp + 1 tsp Polycose powder in 1 L (4 1/4 cups) of distilled water . Mix formulas with sugar-free flavorings as needed for palatability .

Supplemental calcium is given routinely because of both diet, but patients with steatorrhea and bile acid depletion reduced intestinal absorption and the limited calcium content have difficulty absorbing fat-soluble vitamins . Vitamin K of low-lactose diets . Plasma levels of calcium are usually deficiency is rarely a clinical problem unless patients are maintained by mobilizing bone stores unless there is concur- receiving antibiotics . However, large doses of vitamins A, D, rent magnesium or vitamin D deficiency . Therefore, urinary and E may be required to maintain normal body concentra- calcium excretion, which should be greater than 50 mg in 24 tions. Liquid vitamins present in water-miscible and water- hours, is a more reliable index of calcium status . Most pa- soluble forms are more effective than are standard vitamins tients require approximately 1 .5 to 2 g of elemental calcium in pill form . An assessment of vitamin status should be used daily. Although it has been suggested that calcium citrate is to guide therapy . absorbed better than calcium carbonate, 114 most studies do Parenteral nutrition may be neces- not demonstrate any differences in calcium bioavailability PARENTERAL FEEDING. sary to provide fluids, specific nutrients, or complete nutri- from calcium ingested as carbonate, citrate, gluconate, lac- tional requirements in patients who cannot maintain normal tate, or sulfate salt .t35, 136 However, the amount of calcium hydration, electrolyte balance, or nutritional status with oral present in each calcium salt differs significantly, which influ- feeding . Some general guidelines are useful in deciding ences the number of tablets needed each day . which patients require parenteral therapy . Patients in whom Trace Minerals . Data regarding trace mineral requirements in urine output is less than I L day are at increased risk for patients with malabsorption disorders are limited . With the developing renal dysfunction and should receive intravenous exception of zinc and iron, absorption of trace minerals from fluids . Adequate levels of certain minerals-such as magne- ingested foods or liquid formulas is often adequate to pre- sium, potassium, and zinc-and fat-soluble vitamins are dif- vent overt deficiency syndromes . Zinc deficiency is common, ficult to maintain with oral feedings in patients with severe and often subclinical, in patients with malabsorption . Large steatorrhea or large intestinal fluid output and may require dosages of oral zinc supplements may become necessary, parenteral supplementation . Magnesium sulfate can be in- because zinc losses are often high and zinc absorption is jected intramuscularly at a dose of 12 mmol (290 mg of low . Zinc gluconate is tolerated well and does not cause the elemental magnesium) one to three times per week if at- gastric distress caused by zinc sulfate . Zinc should not be tempts at oral therapy are unsuccessful . Intravenous infusion given with meals, because absorption is reduced by food ."' of magnesium is preferred, however, because intramuscular Daily zinc supplementation of 25 mg plus an additional 100 injections are painful and can cause sterile abscesses . mg/L (or 100 mg/kg) of ostomy or diarrheal output is Monthly intramuscular injections of vitamin B 12 (200 mg/ needed to maintain zinc homeostasis . 138 Thus, many patients month) are required in patients who have evidence of vita- require approximately 150 mg of elemental zinc per day . min B 12 malabsorption . In patients who have evidence of, or Although zinc ingestion reduces copper absorption and can are at high risk for, vitamin K-associated hypoprothrombin- cause clinically significant copper deficiency, 139 additional emia, 5 to 10 mg of vitamin K should be given intramuscu- copper intake usually is not needed because of the low larly or intravenously each week . In some patients, total efficiency of zinc absorption . Treating iron deficiency with parenteral nutrition may be lifesaving or may be needed to oral preparations can be difficult . We recommend a liquid limit diarrhea and achieve an acceptable quality of life . form of ferrous sulfate (300 mg/5 mL containing 60 mg of elemental iron) mixed in orange juice four times per day . Diluting ferrous sulfate liquid prevents staining of teeth, and REFERENCES the ascorbic acid present in orange juice enhances iron ab- 1 . Martin WH, Klein S : Use of endogenous carbohydrate and fat as fuels sorption . Some patients, however, require intermittent admin- during exercise . Proc Nutr Soc 57 :49, 1998 . istration of parenteral iron . 2. Harris JA, Benedict FG : Standard basal metabolism constants for physiologists and clinicians . In A Biometric Study of Basal Metabo- Vitamins . Patients with malabsorption can usually absorb ad- lism in Man . Publication 279, The Camegie Institute of Washington . equate amounts of most water-soluble vitamins from their Philadelphia, JB Lippincott, 1919, p 223 .