Advertisement

A primer of nutritional support for gastroenterologists

      Abstract

      GASTROENTEROLOGY 2002;122:1677-1687

      Abbreviations:

      BMI (body mass index), CPN (central parenteral nutrition), HPN (home parenteral nutrition), PEM (protein-energy malnutrition), TEE (total energy expenditure)
      Ingestion and absorption of a nutritionally adequate diet is necessary to maintain normal body composition and organ function. Patients with gastrointestinal diseases are at increased risk for developing nutritional abnormalities from anorexia, dietary restrictions, malabsorption, increased intestinal losses, or altered nutrient requirements. Therefore, it is important for gastroenterologists to understand the general principles of clinical nutrition for optimal management of patients with diseases of the gastrointestinal tract. The purpose of this review is to provide gastroenterologists with information on the basic principles of nutritional support, including metabolic principles, evaluation of nutritional status, indications for nutritional support, appropriate initiation and monitoring of nutritional therapy, and effective management of nutrition-related complications.

      Metabolic principles

       Energy expenditure

      Daily total energy expenditure (TEE) comprises resting energy expenditure, thermic effect of food, and energy expenditure of physical activity.
      Resting energy expenditure, the energy expended during postabsorptive resting conditions, constitutes approximately 70% of TEE. Approximately 75% of the energy consumed at rest is used by the liver, gut, brain, kidneys, and heart, which together constitute only 10% of total body weight. Malnutrition and hypocaloric feeding decrease resting energy expenditure to values 15% to 20% below that expected for a person's actual body size. In contrast, conditions that increase metabolic stress, such as inflammatory diseases or trauma, often increase energy requirements. However, illness or injury only rarely increases resting energy expenditure by more than 50% of pre-illness values.
      The thermic effect of food represents the increase in energy expenditure associated with digestion, absorption, storage, and increased sympathetic nervous system activity after eating. Usually a mixed meal will increase metabolic rate for several hours, expending approximately 8% of ingested calories.
      Energy expenditure of physical activity is the energy consumed to perform mechanical work. The total energy consumed during physical activity depends on the intensity, muscle involvement, and duration of the activity. High-intensity exercise can cause a temporary 15-fold increase in energy expenditure above resting values.

       Endogenous energy stores

      Adipose tissue contains the largest fuel reserve in the body. Energy stored as triglyceride in adipose tissue (~120,000 kcal in a 70-kg man) is much greater than that stored as glycogen in liver (400 kcal) or muscle (1600 kcal). The use of adipose tissue as a fuel requires the conversion of adipose tissue triglycerides to fatty acids, which are released into the bloodstream and delivered to other tissues for oxidation. Skeletal muscle also contains a considerable amount of stored fuel in the form of glycogen and triglycerides. During endurance exercise, the glycogen and triglycerides within muscle tissue provide a direct source of energy for working muscles.

       Starvation

      During fasting, a series of metabolic changes occur to decrease energy expenditure, increase the use of adipose tissue triglycerides as a fuel, decrease brain glucose requirements, maintain glucose delivery to glucose-requiring tissues, and conserve body nitrogen. The duration of survival during starvation depends primarily on the amount of endogenous body fat and lean tissue mass. For example, in lean men, death occurs after approximately 2 months of starvation when more than 35% (~25 kg) of body weight is lost.
      • Leiter LA
      • Marliss EB.
      Survival during fasting may depend on fat as well as protein stores.
      In contrast, extremely obese persons can fast for long periods without adverse effects. The longest reported fast is that of a 207-kg man who ingested noncaloric fluids for 382 days and lost 61% (126 kg) of his initial weight.
      • Stewart WK
      • Fleming LW.
      Features of a successful therapeutic fast of 382 days duration.
      Death from starvation usually occurs when a critical body size is reached (body mass index [BMI] of 13 kg/m2 for men and 11 kg/m2 for women)
      • Henry CJ.
      Body mass index and the limits of human survival.
      after marked depletion of endogenous fat and lean tissue.

      Nutrient requirements

       Energy

      Predictive equations can be helpful in estimating a patient's energy needs. The Harris–Benedict Equation
      • Harris JA
      • Benedict FG.
      Standard basal metabolism constants for physiologists and clinicians..
      provides a reasonable estimate of resting energy expenditure (in kcal/day) in healthy adults, and Men = 66 + (13.7 × weight in kg) + (5 × height in cm) − (6.8 × age in years), and Women = 665 + (9.6 × weight in kg) + (1.8 × height in cm) − (4.7 × age in years).
      A correlated body weight should be used for patients with edema or ascites. Also, an adjusted body weight rather than actual body weight should be used in obese patients (BMI ≥ 30 kg/m2) to avoid overfeeding. Adjusted body weight is equal to ideal body weight + ([actual body weight − ideal body weight] × [0.25]). Adding 10%–20% to the value obtained from the Harris–Benedict calculation (for activity and thermic effect of food) is a reasonable goal for normal-weight patients who are not critically ill. Providing total daily calories equal to the Harris–Benedict calculation should be considered in obese and critically ill patients. An additional 300–500 kcal should be added to the Harris–Benedict estimate in patients who are underweight (BMI <18.5 kg/m2), unless they are critically ill.
      We have developed a simple approach, based on BMI, for estimating energy intake in hospitalized patients (Table 1).
      Table 1Suggested energy requirements for hospitalized patients based on BMI
      BMI (kg/m2)Energy requirements (kcal · kg−1 · d−1)
      <1536–45
      15–1931–35
      20–2926–30
      ≥3015–25
      NOTE. The lower range within each category should be considered in a critically ill patient, unless he or she is depleted in body fat, to decrease the risk of hyperglycemia and infection associated with overfeeding.
      This approach permits making a rapid estimate of initial energy administration and reduces the risk of overfeeding. However, energy intake in specific patients should be modified based on clinical factors and observed responses to nutritional therapy.

       Protein

      The average daily protein requirement for adults is 0.6 g/kg, with a standard deviation of 12.5%. Therefore, a protein intake of 0.75 g/kg meets the requirements of 97% of the adult population and is the basis for the U.S. Recommended Dietary Intake of 0.8 g/kg per day. However, protein requirements are affected by the amount of nonprotein calories consumed (e.g., protein requirements increase when energy intake is inadequate), TEE (protein requirements usually increase with increased energy requirements), and protein quality (an inadequate amount of any of the essential amino acids decreases the efficiency of protein use). Table 2 lists suggested protein requirements for hospitalized patients.
      • Klein S.
      Nutritional therapy.
      Table 2Recommended daily protein intake in adults
      Clinical conditionProtein requirements (g · kg IBW−1 · d−1)
      Normal0.8
      Metabolic stress (illness/injury)1.0–1.5
      Acute renal failure (undialyzed)0.8–1.0
      Hemodialysis1.2–1.4
      Peritoneal dialysis1.3–1.5
      NOTE. Additional protein intake may be needed to compensate for excess protein loss in certain patient groups, such as those with burn injury, open wounds, and protein-losing enteropathy or nephropathy. Decreased protein intake may be necessary in patients with chronic renal insufficiency who are not being treated with dialysis and in patients with hepatic encephalopathy.
      IBW, ideal body weight.
      Adapted and reprinted with permission from Klein S. Nutritional therapy. In: Ahya S, Flood K, Paranjothi S, eds. The Washington manual of medical therapeutics. 30th ed. Philadelphia, Lippincott Williams & Wilkins, 2000:27–42.

       Lipids

      Dietary lipids are composed primarily of triglycerides, which contain saturated and unsaturated long-chain fatty acids. Although most fatty acids can be synthesized by the liver, some fatty acids are essential (i.e., linoleic acid and linolenic acid) because they cannot be synthesized by humans. Obtaining at least 2% of total energy intake from linoleic acid and 0.5% as linolenic acid is needed to prevent essential fatty acid deficiency.

       Carbohydrate

      There is no absolute dietary requirement for carbohydrate, because glucose can be synthesized from endogenous precursors, amino acids, and glycerol. However, glucose is a necessary fuel for certain tissues (e.g., erythrocytes, leukocytes, bone marrow, eye tissues, renal medulla, peripheral nerves), because these tissues cannot metabolize fatty acids. In addition, the brain normally uses glucose as a fuel, but switches to ketone bodies when plasma ketones are increased (e.g., in starvation). Providing approximately 160 g of carbohydrate per day for the brain (~120 g/day) and glucose-requiring tissues (~40 g/day) can spare the breakdown of protein to provide amino acids for gluconeogenesis.

      Protein–energy malnutrition

      Protein–energy malnutrition (PEM) is a term used to describe the clinical effects of inadequate protein and energy intake, including biochemical alterations, impaired organ function, and depletion of body tissues.
      • Klein S.
      Protein-energy malnutrition.
      Primary PEM (e.g., kwashiorkor, marasmus, nutritional dwarfism in children) is caused by impaired access to adequate food intake and occurs most commonly in children and elderly persons. Secondary PEM (e.g., cancer, acquired immunodeficiency syndrome, rheumatologic disease) is caused by illness or injury that alters appetite, digestion, absorption, or nutrient metabolism. Patients with secondary PEM experience wasting from both inadequate nutrient intake and metabolic abnormalities associated with the underlying disease. The clinical manifestations of primary PEM often can be completely corrected by nutritional therapy, but prolonged primary PEM can cause irreversible changes in organ function and growth. Muscle wasting is usually greater in patients with secondary PEM than in those with primary PEM because of alterations in metabolism. Restoration of muscle mass is unlikely with nutritional support alone unless the underlying inflammatory disease is corrected. In fact, most of the weight gained after nutritional support is provided to patients with secondary PEM is caused by increases in fat mass and body water without significant increases in lean tissue.
      • Shike M
      • Russel DM
      • Detsky AS
      • Harrison JE
      • McNeill KG
      • Shepherd FA
      • Feld R
      • Evans WK
      • Jeejeebhoy KN.
      Changes in body composition in patients with small-cell lung cancer. The effect of total parenteral nutrition as an adjunct to chemotherapy.
      The characteristics of the 3 major clinical syndromes of PEM in children (kwashiorkor, marasmus, and nutritional dwarfism) are outlined in Table 3. The presence of peripheral edema distinguishes children with kwashiorkor from those with marasmus and nutritional dwarfism. Kwashiorkor occurs when there is physiologic stress, such as an infection, in an already malnourished child. Leaky cell membranes permit the movement of intracellular ions into the extracellular space, causing water movement and edema. In addition, children with kwashiorkor have a protuberant abdomen because of weakened abdominal muscles, intestinal distention, and hepatomegaly, but do not have ascites. Marasmus is characterized by marked depletion of subcutaneous fat and muscle mass, whereas nutritional dwarfism typically involves failure to thrive, with normal weight for height but short stature and delayed sexual development.
      Table 3Features of PEM syndromes in children
      KwashiorkorMarasmusNutritional dwarfism
      Weight for age (% of expected)60–80<60<60
      Weight for heightNormal or decreasedMarkedly decreasedNormal
      EdemaPresentAbsentAbsent
      MoodIrritable when picked up; apathetic when aloneAlertAlert
      AppetitePoorGoodGood
      PEM can affect the mass and function of many organ systems (Table 4).
      Table 4Effect of severe PEM on tissue mass and function
      Organ systemEffects of PEM
      Gastrointestinal tractMucosal atrophy, decreased liver and pancreas masses; decreased motility with abdominal distention; decreased mucosal and pancreatic enzyme secretion
      SkinDry, thin, wrinkled, and friable
      HairThin, sparse, and easily pulled out; loss of axial and pubic hair in adults; long eyelashes and excessive lanugo hair in children
      HeartDecreased cardiac mass, bradycardia, decreased stroke volume
      Skeletal muscleDecreased mass, muscle weakness, impaired pulmonary function
      Adipose tissueMarked depletion
      KidneysDecreased mass, glomerular filtration rate, ability to secrete acid and sodium, and ability to concentrate urine
      Bone marrowSuppression with anemia, leukopenia, and lymphocytopenia
      Immune systemLymphoid tissue atrophy; decreased cell-mediated immunity and gut IgA secretion; impaired bacterial killing due to decreased complement and neutrophil function
      However, the brain's integrity is preserved at the expense of other organs and tissues, and its weight and protein content is maintained during prolonged undernutrition.

      Assessment of nutritional status

       Specific nutrient deficiencies

      A careful history and physical examination and certain routine laboratory tests (e.g., hemoglobin concentration with red blood cell indices, serum potassium concentration) can identify specific nutrient deficiencies. Selected diagnostic blood or urine tests can then be performed to further evaluate the status of specific minerals and vitamins.

       Protein–energy malnutrition

      The manifestations of PEM differ between children and adults. Undernutrition affects growth and development and causes stunting in children, but primarily causes wasting in adults. Thus, pediatric growth charts and assessment of specific clinical features (Table 3) are useful for diagnosing PEM in children. It is more difficult to diagnose PEM in adults than in children because there is no “gold standard” for evaluating nutritional status. Moreover, many nutritional assessment parameters are affected by illness and injury, making it difficult to separate the influence of the disease itself from inadequate nutrient intake. In fact, all commonly used indicators of PEM malnutrition in hospitalized adults have been validated by their correlation with clinical outcome, rather than by their ability to identify correctable nutritional abnormalities. Nonetheless, a careful clinical evaluation, including a nutritional history and physical examination in conjunction with appropriate laboratory studies, can help detect patients at nutritional risk.

       History

      A nutritional history provides insight into the patient's current nutritional status, willingness and ability to tolerate oral or enteral feeding, and future ability to assimilate adequate nutrients through the gastrointestinal tract. The key features of the interview should include an assessment of body weight and weight loss, current and previous dietary intake, current and future gut function, functional status, and metabolic stress associated with illness or injury.
      • Detsky AS
      • McLaughlin JR
      • Baker JP
      • Johnston N
      • Whittaker S
      • Mendelson RA
      • Jeejeebhoy KN.
      What is subjective global assessment of nutritional status?.
      Unintentional weight loss is a good prognosticator of clinical outcome.
      • DeWys WD
      • Begg C
      • Lavin PT
      • Band PR
      • Bennett JM
      • Bertino JR
      • Cohen MH
      • Douglass Jr, HO
      • Engstrom PF
      • Ezdinli EZ
      • Horton J
      • Johnson GJ
      • Moertel CG
      • Oken MM
      • Perlia C
      • Rosenbaum C
      • Silverstein MN
      • Skeel RT
      • Sponzo RW
      • Tormey DC.
      Prognostic effect of weight loss prior to chemotherapy in cancer patients.
      • Stanley KE.
      Prognostic factors for survival in patients with inoperable lung cancer.
      The severity of unintentional weight loss in the last 6 months is an important predictor of clinical outcome and can be classified as moderate (5%–10%) or severe (>10%). More recent changes in weight, independent of edema or ascites, are important for determining recent trends. A diet history is necessary to determine whether food intake has changed and is adequate, what factors are responsible for any changes, and when current problems will resolve sufficiently to permit adequate intake. Assessment of any active gastrointestinal diseases is important, because diseases of the gastrointestinal tract can have a considerable impact on food intake and nutrient absorption. It is also important to determine whether decreased food intake has been severe enough to lead to compromised physical function and altered daily activities. Finally, the severity of illness affects nutrient requirements. Patients with high metabolic stress may have increased energy and protein requirements but are also more likely to be insulin resistant and unable to tolerate high carbohydrate loads.

       Physical examination

      Table 5Body weight–associated disease risk
      Weight classBMI (kg/m2)Risk
      Extreme underweight≤14.0Extremely high
      Underweight14.1–18.4Increased
      Normal18.5–24.9Normal
      Overweight25.0–29.9Increased
      Obesity
      I30.0–34.9High
      II35.0–39.9Very high
      III≥40.0Extremely high
      Adapted and reprinted with permission from Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—The evidence report. National Institutes of Health, National Heart, Lung, and Blood Institute. Obes Res 1998;6(S2):S53.

       Serum proteins

      The concentrations of specific proteins in the bloodstream, such as albumin and the retinol-binding–prealbumin complex, have been proposed as markers of nutritional status, because they often correlate with clinical outcome. However, serum protein concentration is not a good marker of nutritional status per se, because illness or injury may be responsible for low concentrations.
      • Klein S.
      The myth of serum albumin as a measure of nutritional status.
      For example, inflammation decreases albumin synthesis, increases albumin degradation, and increases albumin transcapillary losses from the plasma compartment.

      Nutritional therapy

       Treatment of selected mineral deficiencies

       Calcium deficiency

      For patients with symptomatic hypocalcemia (tetany), 1 g of calcium gluconate (4.65 mEq or 90 mg of elemental calcium) or 1 g of calcium chloride (13.6 mEq or 272 mg of elemental calcium) should be administered over 10 minutes. An additional 1–2 g can then be given every hour until serum calcium concentration has returned toward normal. Calcium chloride should be given only through a central line to avoid the high risk of thrombophlebitis when administered through a peripheral vein.

       Phosphorous deficiency

      Patients with serum phosphorous concentration <1 mg/dL should be given 0.3 mmol/kg of potassium phosphate or sodium phosphate (containing approximately 4 mEq of potassium or sodium and 3 mmol/L of phosphorous/mL) dissolved in 250 mL of 0.9% saline or 5% dextrose over 4–6 hours. The phosphorous dose should be decreased by 50% if creatinine clearance is <50 mL/min.

       Magnesium deficiency

      In patients with normal renal function, up to 50 mEq (6 g) of magnesium dissolved in 50–100 mL of 0.9% saline or 5% dextrose can be administered intravenously over 4–6 hours.

       Potassium deficiency

      Intravenous potassium salt (KCl), diluted to 20–40 mEq/L, can be given at rates of up to 40 mEq/h in patients with severe potassium depletion when observed by cardiac monitoring. If cardiac monitoring is not available, then the infusion rate should not exceed 20 mEq/h.

       Oral nutrition

       Hospital diets

      Table 6Characteristics of modified hospital diets
      DietCharacteristics
      Modified in Nutrients
      Low-fiber/residueEggs, tender meats, milk, white bread or rice, strained juices, cooked vegetables, and cooked or canned fruits. No nuts, seeds, or skins are allowed.
      High-fiberTotal daily fiber intake of >20 g/day by increasing the intake of whole grains, raw fruits, and vegetables
      Low-fatRestricts fat to <50 g/day
      Low-sodiumRestricts sodium to <2000 mg/day
      Low-proteinRestricts protein to <60 g/day or <0.8 g/kg body weight. A low-protein diet often cannot meet all nutrient needs when protein is limited to ≤40 g/day, so vitamin and mineral supplementation is required.
      Modified in Consistency
      Clear liquidClear juices, broth, Jello, and popsicles
      Full liquidCream soups, milk, and ice cream. This diet contains lactose and is often high in fat.
      PureedFoods blended to baby food consistency
      Mechanical softGround meat with gravy, soft cooked vegetables, canned fruit
      Selected softMeat, fruit, and vegetables chopped into bite-size pieces
      SoftRegular-textured foods omitting fresh fruits and vegetables
      Adapted and reprinted with permission from Klein S, Rubin D. Enteral and parenteral nutrition. In: Feldman M, Freidman L, Sleisenger M, eds. Sleisenger & Fordtran's gastrointestinal and liver disease, 7th ed. Philadelphia, Saunders, 2002, in press.

       Meal supplements

      High-calorie drinks, shakes, and puddings can be used to increase total protein and energy intake in patients willing and able to comply with a supplemental feeding regimen.

       Oral rehydration solutions

      Table 7Characteristics of selected oral rehydration solutions
      ProductNa (mEq/L)K (mEq/L)Cl (mEq/L)Citrate (mEq/L)kcal/LCHO (g/L)mOsm
      Equalyte78 m22681900 mg10025305
      CeraLyte 707020983016540235
      CeraLyte 909020983016540260
      Pedialyte4520353010020300
      Rehydralyte7419643010025305
      Gatorade203N/AN/A21045330
      WHOa902080308020200
      Washington Universityb1050100108520250
      aWHO (World Health Organization) formula: Mix¾ tsp sodium chloride,½ tsp sodium citrate,¼ tsp potassium chloride, and 4 tsp glucose (dextrose) in 1 L (4-¼ cups) of distilled water. bWashington University formula: Mix¾ tsp sodium chloride,½ tsp sodium citrate, and 3 tbsp + 1 tsp Polycose powder in 1 L (4-¼ cups) of distilled water.
      NOTE. Mix formulas with sugar-free flavorings to increase palatability.

       Principles of enteral and parenteral nutritional support

      Patients unable or unwilling to consume adequate nutrients for a prolonged period by oral intake require nutritional therapy to prevent the adverse effects of malnutrition. However, the precise definitions of “adequate” and “prolonged” are not clear and depend on the amount and type of inadequate nutrient intake, the amount of existent endogenous fuel (fat) and muscle mass, and the rate of catabolism of those endogenous stores. In general, enteral or parenteral nutrition should be considered if energy intake has been, or is anticipated to be, inadequate (<25% of daily requirements) for 10–14 days in normal-weight adults. However, the safety and efficacy of this recommendation has not been tested in clinical trials.

       Defined formula diets

      Defined liquid formulas are products with a “defined” nutrient content, which can be classified by their protein/amino acid content as monomeric, oligomeric, and polymeric formulas. Monomeric formulas, also known as elemental diets (e.g., Vivonex [Novartis, Minneapolis, MN]), contain nitrogen in the form of free amino acids, carbohydrates as glucose polymers, and minimal amounts of fat as long-chain triglycerides. These formulas are usually unpalatable and require flavoring or a feeding tube to achieve dietary compliance. Oligomeric formulas, also known as semi-elemental diets (e.g., Vital [Ross Laboratories, Columbus, OH] and Peptamen [Nestle, Deerfield, IL]), contain hydrolyzed proteins with different lengths of small peptides and, in some formulas, free amino acids. Polymeric formulas include milk-based and lactose-free formulas that contain nitrogen in the form of whole protein. These formulas are available as standard iso-osmolar solutions, containing approximately 1 kcal/mL, 16% calories as protein, 55% calories as carbohydrate, and 30% calories as fat (e.g., Osmolite, Ensure [both Ross Laboratories], Isocal [Mead Johnson, Evansville, IN]). In addition, formulas with modifications in nutrient content, such as high-calorie (e.g., Two Cal HN [Ross Laboratories]) and fiber-enriched (e.g., Jevity [Ross Laboratories]) formulas are available for specific clinical needs.
      The indications for monomeric and oligomeric formulas, which are usually more expensive than polymeric formulas, are not clear. Even in patients with short-bowel syndrome and impaired absorptive function, nitrogen balance with a monomeric or oligomeric formula is no better than with polymeric formula feeding.
      • McIntyre PB
      • Fitchew M
      • Lennard-Jones JE.
      Patients with a high jejunostomy do not need a special diet.
      • Cosnes J
      • Evard D
      • Beaugerie L
      • Gendre JP
      • Quintrec YL.
      Improvement in protein absorption with a small-peptide-based diet in patients with high jejunostomy.

       Enteral tube feeding

      Enteral tube feeding can provide nutritional support in patients who cannot or will not eat but who have a functional gastrointestinal tract. The placement of a small-diameter nasogastric or nasoduodenal tube is the simplest technique for feeding patients who are unlikely to require tube feedings for more than 6 weeks. Gastrostomy, gastrojejunostomy, and jejunostomy tubes placed by using endoscopic, radiologic, or surgical techniques should be considered in patients who require longer-term feeding.
      When the tip of the feeding tube is in the stomach, feedings can be given intermittently by bolus or gravity technique, 4–6 times per day. Bolus feedings are injected by syringe as rapidly as tolerated and gravity feedings are infused over 30–60 minutes. The patient's upper body should be elevated by 30°–45° during feeding and for at least 2 hours after feeding to decrease the risk of aspiration. Tubes should be flushed with water after each feeding, and pill fragments or “thick” medications should be avoided to prevent clogging. Intermittent, rather than continuous, feedings are useful for patients who desire more freedom from feeding and who cannot be positioned with continuous upper-body elevation. Patients who experience abdominal pain, nausea, and bloating with bolus gravity feedings may require continuous infusion at a slower rate. Patients who have gastroparesis can often tolerate gastric tube feedings when started at a slow rate (e.g., 10 mL/hour) and advanced by small increments (e.g., 10 mL/hour every 8–12 hours). However, those who have severe gastroparesis may require postpyloric feeding. Continuous feeding should always be used when feeding directly into the duodenum or jejunum to avoid distention, abdominal pain, and dumping syndrome.

       Tube feeding complications

      Mechanical complications of tube feeding include tracheobronchial intubation, erosive tissue damage, and tube occlusion. Tube occlusion can be treated by using a small volume syringe (10 mL) to flush warm water or pancreatic enzymes (e.g., Viokase [Axcan Scandipharm, Birmingham, AL] dissolved in water) through the tube in attempts to unclog obstructions. However, the pressure that can be generated with small volume syringes is sufficient to rupture feeding tubes. Commercially made products that either dissolve or mechanically remove inspissated feedings are also available.
      The metabolic complications associated with tube feeding include electrolyte abnormalities and increased blood glucose in patients with diabetes. Adequate blood glucose control in patients with type 2 diabetes can be achieved by administering subcutaneous insulin. Once tube feedings reach 1000 kcal/day, intermediate-duration insulin can usually be given safely. Intermediate-duration insulin can be given every 12 hours in patients receiving continuous (24-hour) feeding. Blood glucose excursions should be covered with regular insulin by using a sliding-scale algorithm designed to meet each patient's specific needs.
      The most common pulmonary complication associated with tube feeding is aspiration. It can be difficult to distinguish aspiration of refluxed feedings from aspiration of oropharyngeal secretions. Adding several drops of blue food coloring to the feeding formula and evaluating the color of respiratory secretions can help determine whether tube feedings are involved. However, this approach must be used with caution because of several case reports suggesting that food coloring is absorbed by the gastrointestinal tract in critically ill patients, resulting in hypotension, metabolic acidosis, and death.
      • Maloney JP
      • Halbower AC
      • Fouty BF
      • Fagan KA
      • Balasubramaniam V
      • Pike AW
      • Fennessey PV
      • Moss M.
      Systemic absorption of food dye in patients with sepsis.
      Gastrointestinal complications of tube feedings include nausea, vomiting, abdominal pain, diarrhea, and, rarely, bowel necrosis. Diarrhea is common in critically ill patients who are given tube feedings; however, this diarrhea is often caused by antibiotics or enteral administration of nonabsorbable carbohydrates (e.g., sorbitol) in liquid medications, rather than by the tube feedings per se.
      • Edes TE
      • Walk BE
      • Austin JL
      Diarrhea in tube-fed patients: feeding formula not necessarily the cause.
      Nonocclusive bowel necrosis has been reported in 0.3% of critically ill patients receiving tube feedings, particularly those also receiving vasoconstrictive medications to maintain blood pressure.
      • Marvin RG
      • McKinley BA
      • McQuiggan M
      • Cocanour CS
      • Moore FA.
      Nonocclusive bowel necrosis occurring in critically ill trauma patients receiving enteral nutrition manifests no reliable clinical signs for early detection.
      Necrosis is presumably related to feeding-induced increases in mucosal oxygen requirements in the presence of compromised gastrointestinal blood flow.

       Central parenteral nutrition

      Central parenteral nutrition (CPN), also known as total parenteral nutrition, is given through a large, high-flow central vein because of the high osmotic load delivered by the nutrient solution. The most common technique for catheter placement is percutaneous infraclavicular subclavian vein catheterization with advancement of the catheter tip to the junction of the superior vena cava and right atrium. Internal jugular vein catheterization decreases the risk of pneumothorax, but is associated with decreased patient comfort and difficulty maintaining sterility. The use of peripherally inserted central venous catheters also eliminates the risk of pneumothorax, but these can be used only in patients with adequate antecubital vein access.
      Approximately 80 prospective randomized controlled trials have evaluated the clinical efficacy of CPN under varying clinical conditions.
      • Koretz RL
      • Lipman TO
      • Klein S.
      American Gastroenterological Association technical review: parenteral nutrition.
      Although preoperative CPN was associated with a decreased rate of postoperative complications in patients undergoing surgery for cancer of the esophagus or stomach,
      • Koretz RL
      • Lipman TO
      • Klein S.
      American Gastroenterological Association technical review: parenteral nutrition.
      • Satyanarayana R
      • Klein S.
      Perioperative nutrition.
      most studies were unable to identify a consistent beneficial effect of CPN on morbidity or mortality. However, many trials excluded patients who might benefit most from nutritional support (i.e., those with severe weight loss), because it was considered unethical to enroll them in clinical trials that might prevent them from receiving nutritional support. Therefore, despite the large number of trials, the data are inadequate to assess the efficacy of parenteral nutrition in patients who are severely malnourished or who have highly catabolic disease processes.
      Long-term home parenteral nutrition (HPN) is usually provided through catheters inserted into the subclavian vein and tunneled subcutaneously to exit directly from the anterior chest wall or through implantable subcutaneous ports. The clinical outcome of a patient receiving HPN depends on whether the patient has a benign or a terminal illness.
      • Howard L
      • Ament M
      • Fleming CR
      • Shike M
      • Steiger E.
      Current use and clinical outcome of home parenteral and enteral nutrition therapies in the United States.
      Less than 50% of patients receiving HPN who have cancer are usually alive at 6 months, and only 10% are alive at 1 year. In contrast, ~70% of patients with benign diseases achieve complete rehabilitation, and the 1-year survival rate is close to 90%.

       Parenteral nutrient solutions

      CPN can be given as a 3-in-1 admixture, containing protein, carbohydrate, and fat, or the lipid component can be given as a separate solution piggybacked to the primary amino acid and dextrose solution. The use of an admixture decreases handling costs and potential breaks in sterility, but makes visual detection of small precipitates very difficult.
      The nitrogen source in CPN is crystalline amino acids, containing all essential and most nonessential amino acids. These amino acid formulations contain little or no glutamine, glutamate, aspartate, asparaginine, tyrosine, and cysteine. Some solutions have been modified for specific disease states, for example, solutions enriched with branched-chain amino acids for patients who have hepatic encephalopathy, and solutions containing mostly essential amino acids for patients with renal insufficiency. But these formulations are more expensive than standard amino acids, and they have limited indications for use. Branched-chain amino acid–enriched solutions permit greater amino acid intake (60–80 grams per day) with less risk of encephalopathy than standard formulas.
      • Naylor CB
      • O'Rourke K
      • Detsky AS
      • Baker JP.
      Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy: a meta-analysis.
      The superiority of administering essential amino acids as the sole source of nitrogen over solutions containing a mixture of essential and nonessential amino acids has not been demonstrated in prospective randomized trials.
      Dextrose (glucose) is the least expensive source of energy in parenteral nutrition. The amount of infused dextrose that is oxidized is directly proportional to the amount administered until a threshold level is reached. For example, in stable postoperative patients, dextrose infusion at a rate exceeding 6 mg/kg per minute did not increase the rate of glucose oxidation.
      • Wolfe RR
      • O'Donnell Jr, TF
      • Stone MD
      • Richmond DA
      • Burke JF.
      Investigation of factors determining the optimal glucose infusion rate in total parenteral nutrition.
      Providing excessive glucose calories can have adverse consequences on glucose control, liver metabolism, and lung function; respiratory acidosis has been reported in patients with pulmonary insufficiency due to increased carbon dioxide production.
      • Covelli HD
      • Black JW
      • Olsen MS
      • Beckman JF.
      Respiratory failure precipitated by high carbohydrate loads.
      Lipid emulsions are iso-osmolar solutions that contain triglycerides derived from soybean oil or a combination of soybean and safflower oil. The triglycerides are predominantly composed of essential fatty acids, linoleic acid, and linolenic acid. The optimal percentage of calories that should be infused as fat is not known, but 20%–30% of total calories is reasonable for most patients. A minimum of ~5% of total calories as a lipid emulsion is necessary to prevent essential fatty acid deficiency in patients receiving continuous CPN. The lipid infusion rate should not exceed 1.0 kcal/kg per hour (0.11 g/kg per hour) to reduce the risk of pulmonary dysfunction, impaired reticuloendothelial system function, decreased platelet aggregation, and fat-overload syndrome, which has been reported when this infusion rate is exceeded.
      • Miles JM.
      Intravenous fat emulsions in nutritional support.
      Lipid emulsions should not be given to patients with serum triglyceride concentration >400 mg/dL, to prevent severe hypertriglyceridemia and pancreatitis.

       Complications of CPN

      CPN is associated with procedural, metabolic, vascular, infectious, hepatobiliary, and bone complications. The risk of most complications can be reduced by ensuring that an experienced team supervises the administration of nutritional support.
      • Payne-James J.
      Cost-effectiveness of nutrition support teams. Are they necessary?.
      Procedural complications include damage to local structures (e.g., pneumothorax, brachial plexus injury, subclavian and carotid artery puncture, hemothorax, thoracic duct injury) and technical complications (e.g., catheter advancement into the internal jugular vein, air embolism) during attempted venous cannulation.
      Metabolic complications (i.e., fluid overload, hypertriglyceridemia, hypercalcemia, hypoglycemia, hyperglycemia, specific nutrient deficiencies) are usually caused by inappropriate nutrient administration. Hyperglycemia should be corrected, because poor glucose control is associated with dysfunction of leukocytes and complement and with increased risk of infection.
      • Van den Berghe G
      • Wouters P
      • Weekers F
      • Verwaest C
      • Bruyninckx F
      • Schetz M
      • Vlasselaers D
      • Ferdinande P
      • Lauwers P
      • Bouillon R.
      Intensive insulin therapy in critically ill patients.
      Therefore, in stable patients, blood glucose level should be maintained between 100 and 150 mg/dL. In pregnant patients, blood glucose level should be kept below 120 mg/dL, to avoid complications of gestational diabetes and large-for-gestational-age birth. If a patient's blood glucose is >200 mg/dL, better glucose control should be obtained before starting CPN. The therapeutic approach outlined in Table 8 should be considered for hyperglycemic patients receiving CPN.
      • McMahon MM
      • Rizza RA.
      Nutrition support in hospitalized patients with diabetes mellitus.
      Table 8Management of hyperglycemia in patients receiving parenteral nutrition
      If blood glucose level is >200 mg/dL:
       Limit dextrose to <200 g/day.
       Add 0.1 unit of insulin for each gram of dextrose in the CPN solution (e.g., 15 units for 150 g).
       Discontinue other sources of IV dextrose.
       Order subcutaneous sliding-scale regular insulin with blood glucose monitoring by fingerstick every 4–6 hours or sliding-scale IV regular insulin infusion with blood glucose monitoring by fingerstick every 1–2 hours as follows:
       If blood glucose level remains >200 mg/dL and the patient has been receiving subcutaneous insulin, add 50% of the sliding-scale dose of regular insulin given in the last 24 hours to the next day's CPN solution, and double the sliding-scale dose of subcutaneous insulin.
       If blood glucose level remains >200 mg/dL and the patient has been receiving intravenous insulin, add 50% of the IV insulin given in the last 24 hours to the next day's CPN solution, and increase the sliding-scale IV insulin infusion rate by 50%.
      If blood glucose level remains >200 mg/dL, consider the following actions:
       Discontinue CPN until better glucose control can be established.
       Decrease the dextrose content in the CPN solution.
       Initiate an insulin drip.
      Dextrose in CPN may be increased when blood glucose control (100–150 mg/dL) is achieved. The insulin:dextrose ratio in the CPN formulation should be maintained when the CPN dextrose content is changed.
      Adapted and reprinted with permission from Klein S, Rubin D. Enteral and parenteral nutrition. In: Feldman M, Freidman L, Sleisenger M, eds. Sleisenger & Fordtran's gastrointestinal and liver disease, 7th ed. Philadelphia, Saunders, 2002, in press.
      Subclavian vein thrombosis can be detected by careful radiologic studies in 25%–50% of patients receiving CPN.
      • Bozzetti F
      • Scarpa D
      • Terno G
      • Scotti A
      • Ammatuna M
      • Bonalumi MG
      • Ceglia E.
      Subclavian venous thrombosis due to indwelling catheters: a prospective study on 52 patients.
      • Bern MM
      • Lokich JJ
      • Wallach SR
      • Bothe Jr, A
      • Benotti PN
      • Arkin CF
      • Greco FA
      • Huberman M
      • Moore C.
      Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial.
      However, clinically evident thromboses are rare. Fatal microvascular pulmonary emboli caused by calcium and phosphorous precipitates present in total nutrient admixtures have been reported.
      • Hill SE
      • Heldman LS
      • Goo EDH
      • Whippo PE
      • Perkinson JC.
      Case report: fatal microvascular pulmonary emboli from precipitation of a total nutrient admixture solution.
      Lipid emulsions present in total nutrient admixtures can obscure the visible detection of precipitates. Even careful visual inspection of any parenteral nutrient solutions cannot completely prevent the identification of dangerous microprecipitates—the smallest pulmonary capillaries are 5 μm in diameter, but the size limit for visual detection of microprecipitates is 50–100 μm. Therefore, strict pharmacy standards for physical-chemical compatibility must be followed when mixing parenteral nutrition solutions. In-line filters provide an additional safeguard against infusing harmful precipitates. A.22-μm filter should be inserted between the intravenous tubing and the catheter when infusing lipid-free CPN and changed with the tubing; a 1.2-μm filter should be used when infusing a total nutrient admixture containing a lipid emulsion.
      Catheter-related sepsis is the most common serious complication associated with CPN. S. epidermidis and S. aureus are the most common organisms responsible for infection, but in patients who are immunocompromised or receiving long-term (>2 wks) CPN, other organisms (e.g., Enterococcus, Candida species, E. coli, Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Proteus, Xanthomonas) should also be considered. The suggested initial evaluation and therapy of the patient with suspected catheter-related sepsis is outlined in Table 9.

      Klein S, Rubin D. Enteral and parenteral nutrition. In: Feldman M, Freidman L, Sleisenger M, eds. Sleisenger & Fordtran's gastrointestinal and liver disease. 7th ed. Philadelphia: Saunders, in press.

      Table 9Suggested management of patients with suspected catheter-related sepsis
      1. Perform an initial evaluation:
       a. Evaluate the catheter insertion site and culture any drainage.
       b. Obtain blood cultures from the peripheral vein and central vein catheter.
       c. Culture the catheter tip, if removed.
       d. Look for other potential causes of infection.
      2. Stop CPN for 48–72 hours.
      3. Monitor for indications of when to remove a central venous catheter:
       a. Purulent discharge or abscess at the insertion site
       b. Septic shock without another etiology for the source of infection
       c. Persistent or recurrent catheter-related bacteremia
       d. Candida or Pseudomonas infection
       e. Polymicrobial infection
       f. S. aureus infection
      4. If the catheter is “irreplaceable,” consider a trial of antibiotic therapy with the line in place:
       a. Empiric antibiotic therapy with vancomycin and cefepime (if gram-negative infection is suspected) administered through the central venous catheter until culture results are obtained.a
       b. Specific antibiotic therapy administered through the central venous catheter once culture results are available.
       c. The duration of antibiotic therapy usually ranges from 2 to 6 weeks depending on the patient, the infective organism, and whether the central line has been left in place.
      5. Repeat blood cultures in 48 and 72 hours to ensure clearance of bacteremia.
      6. Fever should resolve within 72–96 hours with appropriate antibiotic therapy; remove the catheter if fever persists.
      aThe antibiotic lock technique is an alternative approach that has also been successfully used to treat central catheter infections.
      • Messing B.
      Catheter-sepsis during home parenteral nutrition: use of the antibiotic-lock technique.
      This approach involves injecting an antibiotic solution (e.g., vancomycin 2 mg/mL) into the central venous catheter lumen and allowing the antibiotic to sit for at least 12 hours.
      Adapted and reprinted with permission from Klein S. Nutritional therapy. In: Ahya S, Flood K, Paranjothi S, eds. The Washington manual of medical therapeutics, 30th ed. Philadelphia, Lippincott Williams & Wilkins, 2000:27–42.
      Hepatic abnormalities in patients receiving CPN are more severe and more common in infants than in adults. In adults, most abnormalities are benign and transient, but some patients receiving CPN for more than 16 weeks develop serious and progressive liver disease, including steatohepatitis, fibrosis, and cirrhosis.
      • Klein S.
      Total parenteral nutrition and the liver.
      A liver biopsy is useful to determine the severity of liver disease in patients with persistent abnormalities in liver biochemistries or other evidence of liver damage. The therapeutic approach involves providing a portion (20%–40%) of calories as fat, cycling CPN to stop the glucose infusion for at least 8–10 hours/day, avoiding excessive caloric intake, and administering a trial of therapy with metronidazole or ursodeoxycholic acid. When cholestasis is present, copper and manganese should be removed from the CPN formula to prevent accumulation in the liver and basal ganglia.
      The use of CPN is associated with acalculous cholecystitis, gallbladder sludge, and cholelithiasis. Gallstones rarely occur in patients receiving less than 3 weeks of CPN, and then are usually caused by gallbladder stasis.
      • Messing B
      • Bories C
      • Kunstlinger F
      • Bernier JJ.
      Does total parenteral nutrition induce gallbladder sludge formation and lithiasis?.
      Stimulating gallbladder contraction and emptying with either enteral feedings
      • Roslyn JJ
      • DenBesten L
      • Thompson Jr., JE
      Effects of periodic emptying of gallbladder on gallbladder function and formation of cholesterol gallstones.
      or cholecystokinin injections
      • Sitzmann JV
      • Pitt HA
      • Steinborn PA
      • Pasha ZR
      • Sanders RC.
      Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans.
      reduces or eliminates the risk of gallbladder sludge and gallstone formation.
      Osteomalacia and osteopenia have been observed in patients receiving CPN for more than 3 months. The clinical manifestations of metabolic bone disease range from asymptomatic, radiologic evidence of demineralization to bone pain and bone fracture.
      • Klein GL
      • Coburn JW.
      Parenteral nutrition: effect on bone and mineral homeostasis.

      Refeeding the severely malnourished patient

      Refeeding a patient with severe malnutrition can have adverse clinical consequences collectively known as “refeeding syndrome.”
      • Alpers D
      • Klein S.
      Refeeding the malnourished patient.
      These complications include (1) thiamine deficiency and acute beriberi, (2) fluid overload (edema, congestive heart failure, and pulmonary edema), (3) abnormal serum electrolytes (hypophosphatemia, hypokalemia, and hypomagnesemia), (4) cardiac arrythmias (bradycardia, ventricular tachyarrythmias), (5) glucose intolerance (elevations in blood glucose concentration, glucosuria, dehydration, and hyperosmolar coma), and (6) gastrointestinal dysfunction (nausea, vomiting, diarrhea).
      The risk of refeeding complications is greatest within the first few days of nutritional therapy. Therefore, careful evaluation of fluid status, cardiovascular function, and serum electrolytes should be performed before feeding is initiated to guide the nutritional approach. A thiamine supplement, 50–100 mg daily for 3 days, should be administered. Serious electrolyte abnormalities, particularly hypokalemia and hypophosphatemia, should be corrected before starting nutritional therapy. During the first week of refeeding, fluid intake should be limited to approximately 800 mL/day plus insensible losses, but can be increased or decreased as needed in patients with evidence of dehydration or fluid overload. Monitoring body weight can guide fluid administration; weight gain greater than 0.25 kg/day, or 1.5 kg/week, is likely due to fluid accumulation, not tissue repletion. Initial daily calorie intake should be ~15 kcal/kg, containing ~100 g of carbohydrate and ~ 1.5 g protein · kg−1 · d−1. Sodium should be restricted to approximately 60 mEq or 1.5 g/day, but more liberal amounts can be given to dehydrated patients. Liberal amounts of phosphorus, potassium, and magnesium should be given to patients with normal renal function. All other nutrients should be given in amounts needed to meet the RDI. Body weight, fluid intake, urine output, and plasma glucose and electrolytes should be monitored daily during the early refeeding period, and nutritional therapy should be adjusted based on the results of the daily evaluation.

      References

      1. 9th ed. Modern nutrition in health and disease. Williams & Wilkins, Baltimore, Maryland1999
        • Leiter LA
        • Marliss EB.
        Survival during fasting may depend on fat as well as protein stores.
        JAMA. 1982; 248: 2306-2307
        • Stewart WK
        • Fleming LW.
        Features of a successful therapeutic fast of 382 days duration.
        Postgrad Med J. 1973; 49: 203-209
        • Henry CJ.
        Body mass index and the limits of human survival.
        Eur J Clin Nutr. 1990; 44: 329-335
        • Harris JA
        • Benedict FG.
        Standard basal metabolism constants for physiologists and clinicians..
        A biometric study of basal metabolism in man. Lippincott, Philadelphia, Pennsylvania1919 (Publication 279, The Carnegie Institute of Washington)
        • Klein S.
        Nutritional therapy.
        in: 30th ed. The Washington manual of medical therapeutics. Lippincott Williams & Wilkins, Philadelphia2000: 27-42
        • Klein S.
        Protein-energy malnutrition.
        in: 22nd ed. Cecil textbook of medicine. Castle Connolly, New York2002 (in press)
        • Shike M
        • Russel DM
        • Detsky AS
        • Harrison JE
        • McNeill KG
        • Shepherd FA
        • Feld R
        • Evans WK
        • Jeejeebhoy KN.
        Changes in body composition in patients with small-cell lung cancer. The effect of total parenteral nutrition as an adjunct to chemotherapy.
        Ann Intern Med. 1984; 101: 303-309
        • Detsky AS
        • McLaughlin JR
        • Baker JP
        • Johnston N
        • Whittaker S
        • Mendelson RA
        • Jeejeebhoy KN.
        What is subjective global assessment of nutritional status?.
        J Parenter Enteral Nutr. 1987; 11: 8-13
        • DeWys WD
        • Begg C
        • Lavin PT
        • Band PR
        • Bennett JM
        • Bertino JR
        • Cohen MH
        • Douglass Jr, HO
        • Engstrom PF
        • Ezdinli EZ
        • Horton J
        • Johnson GJ
        • Moertel CG
        • Oken MM
        • Perlia C
        • Rosenbaum C
        • Silverstein MN
        • Skeel RT
        • Sponzo RW
        • Tormey DC.
        Prognostic effect of weight loss prior to chemotherapy in cancer patients.
        Am J Med. 1980; 69: 491-497
        • Stanley KE.
        Prognostic factors for survival in patients with inoperable lung cancer.
        J Natl Cancer Inst. 1980; 65: 25-32
        • Klein S.
        The myth of serum albumin as a measure of nutritional status.
        Gastroenterology. 1990; 99: 1845-1846
        • Lennard-Jones JE.
        Oral rehydration solutions in short bowel syndrome.
        Clin Ther. 1990; 12: 129A-137A
        • McIntyre PB
        • Fitchew M
        • Lennard-Jones JE.
        Patients with a high jejunostomy do not need a special diet.
        Gastroenterology. 1986; 91: 25-33
        • Cosnes J
        • Evard D
        • Beaugerie L
        • Gendre JP
        • Quintrec YL.
        Improvement in protein absorption with a small-peptide-based diet in patients with high jejunostomy.
        Nutrition. 1992; 8: 406-411
        • Maloney JP
        • Halbower AC
        • Fouty BF
        • Fagan KA
        • Balasubramaniam V
        • Pike AW
        • Fennessey PV
        • Moss M.
        Systemic absorption of food dye in patients with sepsis.
        N Engl J Med. 2000; 343: 1047-1048
        • Edes TE
        • Walk BE
        • Austin JL
        Diarrhea in tube-fed patients: feeding formula not necessarily the cause.
        Am J Med. 1990; 88: 91-93
        • Marvin RG
        • McKinley BA
        • McQuiggan M
        • Cocanour CS
        • Moore FA.
        Nonocclusive bowel necrosis occurring in critically ill trauma patients receiving enteral nutrition manifests no reliable clinical signs for early detection.
        Am J Surg. 2000; 179: 7-12
        • Koretz RL
        • Lipman TO
        • Klein S.
        American Gastroenterological Association technical review: parenteral nutrition.
        Gastroenterology. 2001; 121: 970-1001
        • Satyanarayana R
        • Klein S.
        Perioperative nutrition.
        Curr Opin Clin Nutr Metab Care. 1998; 1: 51-58
        • Howard L
        • Ament M
        • Fleming CR
        • Shike M
        • Steiger E.
        Current use and clinical outcome of home parenteral and enteral nutrition therapies in the United States.
        Gastroenterology. 1995; 109: 355-365
        • Naylor CB
        • O'Rourke K
        • Detsky AS
        • Baker JP.
        Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy: a meta-analysis.
        Gastroenterology. 1989; 97: 1033-1042
        • Wolfe RR
        • O'Donnell Jr, TF
        • Stone MD
        • Richmond DA
        • Burke JF.
        Investigation of factors determining the optimal glucose infusion rate in total parenteral nutrition.
        Metabolism. 1980; 29: 892-900
        • Covelli HD
        • Black JW
        • Olsen MS
        • Beckman JF.
        Respiratory failure precipitated by high carbohydrate loads.
        Ann Intern Med. 1981; 95: 579-581
        • Miles JM.
        Intravenous fat emulsions in nutritional support.
        Curr Opin Gastroenterol. 1991; 7: 306-311
        • Payne-James J.
        Cost-effectiveness of nutrition support teams. Are they necessary?.
        Nutrition. 1997; 13: 928-930
        • Van den Berghe G
        • Wouters P
        • Weekers F
        • Verwaest C
        • Bruyninckx F
        • Schetz M
        • Vlasselaers D
        • Ferdinande P
        • Lauwers P
        • Bouillon R.
        Intensive insulin therapy in critically ill patients.
        N Engl J Med. 2001; 345: 1359-1367
        • McMahon MM
        • Rizza RA.
        Nutrition support in hospitalized patients with diabetes mellitus.
        Mayo Clin Proc. 1996; 71: 587-594
        • Bozzetti F
        • Scarpa D
        • Terno G
        • Scotti A
        • Ammatuna M
        • Bonalumi MG
        • Ceglia E.
        Subclavian venous thrombosis due to indwelling catheters: a prospective study on 52 patients.
        J Parenter Enteral Nutr. 1983; 7: 560-562
        • Bern MM
        • Lokich JJ
        • Wallach SR
        • Bothe Jr, A
        • Benotti PN
        • Arkin CF
        • Greco FA
        • Huberman M
        • Moore C.
        Very low doses of warfarin can prevent thrombosis in central venous catheters. A randomized prospective trial.
        Ann Intern Med. 1990; 112: 423-428
        • Hill SE
        • Heldman LS
        • Goo EDH
        • Whippo PE
        • Perkinson JC.
        Case report: fatal microvascular pulmonary emboli from precipitation of a total nutrient admixture solution.
        J Parenter Enteral Nutr. 1996; 20: 81-87
      2. Klein S, Rubin D. Enteral and parenteral nutrition. In: Feldman M, Freidman L, Sleisenger M, eds. Sleisenger & Fordtran's gastrointestinal and liver disease. 7th ed. Philadelphia: Saunders, in press.

        • Klein S.
        Total parenteral nutrition and the liver.
        in: 7th ed. Diseases of the liver. Lippincott, Philadelphia1993: 1505-1516
        • Messing B
        • Bories C
        • Kunstlinger F
        • Bernier JJ.
        Does total parenteral nutrition induce gallbladder sludge formation and lithiasis?.
        Gastroenterology. 1983; 84: 1012-1019
        • Roslyn JJ
        • DenBesten L
        • Thompson Jr., JE
        Effects of periodic emptying of gallbladder on gallbladder function and formation of cholesterol gallstones.
        Surg Forum. 1979; 30: 403-404
        • Sitzmann JV
        • Pitt HA
        • Steinborn PA
        • Pasha ZR
        • Sanders RC.
        Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans.
        Surg Gynecol Obstet. 1990; 170: 25-31
        • Klein GL
        • Coburn JW.
        Parenteral nutrition: effect on bone and mineral homeostasis.
        Ann Rev Nutr. 1991; 11: 93-119
        • Alpers D
        • Klein S.
        Refeeding the malnourished patient.
        Curr Opin Gastroenterol. 2001; 15: 151-153
        • Messing B.
        Catheter-sepsis during home parenteral nutrition: use of the antibiotic-lock technique.
        Nutrition. 1998; 14: 466-471