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Surgical Metabolism & Nutrition
Thomas M. Shary, MD
Emily A. Chapman, RD, LD, CNSC
Virginia M. Herrmann, MD
The effects of malnutrition on the surgical patient are well characterized in the literature but are often overlooked in the clinical arena. Between 30% and 50% of hospitalized patients are malnourished. Protein-calorie malnutrition produces a reduction in lean muscle mass, alterations in respiratory mechanics, impaired immune function, and intestinal atrophy. These changes result in diminished wound healing, predisposition to infection, and increased postoperative morbidity. Although most healthy individuals can tolerate up to 7 days of starvation (with adequate glucose and fluid replacement), those subjected to major trauma, the physiologic stress of surgery, sepsis, or cancer-related cachexia require earlier nutritional intervention. Methods to identify those at greatest need for supplemental nutrition and to adequately address their needs are discussed in this chapter.
NUTRITIONAL ASSESSMENT
Nutrition screening is the process of identifying patients who are either malnourished or at risk for developing malnutrition. Major trauma and surgical stress alter the intake and absorption of nutrients, as well as their utilization and storage by the body. In select patients (eg, those with severe malnutrition as determined below), preoperative nutritional support has been shown to significantly reduce perioperative morbidity and mortality. Although most patients do not require this level of support, nutrition screening is imperative to identify the patient at high risk for malnutrition or its sequelae. A comprehensive nutritional assessment incorporates the initial history, physical examination, and laboratory testing to provide a snapshot of the patient’s recent nutritional health.
History & Physical Examination
The history and physical examination are the foundation of nutritional assessment. A complete medical history is essential to identify factors that predispose the patient to alterations in nutritional status (Table 10–1). Chronic illnesses such as alcoholism are commonly associated with protein-calorie malnutrition as well as vitamin and mineral deficiencies. Previous operative procedures such as gastrectomy or ileal resection may predispose to generalized malabsorption or isolated deficiency of iron, vitamin B12, or folate. In most cases, the possibility of malnutrition is suggested by the underlying disease or by a history of recent weight loss. Patients with renal failure who require hemodialysis lose amino acids, vitamins, trace elements, and carnitine in the dialysate. Cirrhotics often suffer from whole-body sodium overload despite being hyponatremic, and they are typically protein-deficient. Patients with inflammatory bowel disease, particularly those with ileal involvement, may develop protein deficiency due to a combination of poor intake, chronic diarrhea, and treatment with corticosteroids. Furthermore, alterations in the enterohepatic circulation of bile salts lead to fat, vitamin, calcium, magnesium, and trace element deficiencies. Approximately 30% of patients with cancer have protein, calorie, and vitamin deficiencies due either to the underlying disease or to antimetabolite chemotherapy (eg, methotrexate). Patients infected with HIV are frequently malnourished and have protein, trace metal (selenium and zinc), mineral, and vitamin deficiencies.
Table 10–1. Nutritional assessment.
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History (Factors Predisposing to Malnutrition) Absorption disorders (eg, celiac sprue) AIDS Alcoholism Chronic renal insufficiency Cirrhosis Diabetes mellitus Enteric obstruction Inflammatory bowel disease Malignancy Past surgical history, especially involving gastrointestinal tract Prolonged starvation Psychiatric disorders (eg, anorexia nervosa) Recent major surgery, trauma, or burn Severe cardiopulmonary disease Physical Examination Skin: Quality, texture, rash, follicles, hyperkeratosis, nail deformities Hair: Quality, texture, recent loss Eyes: Keratoconjunctivitis, night blindness Mouth: Cheilosis, glossitis, mucosal atrophy (eg, temporal wasting), dentition Heart: Chamber enlargement, murmurs Abdomen: Hepatomegaly, abdominal mass, ostomy, fistulas Rectum: Stool color, perineal fistula, Guaiac test Neurologic: Peripheral neuropathy, dorsolateral column deficit, mental status Extremities: Muscle size and strength, pedal edema Laboratory Tests CBC: Hemoglobin, hematocrit, mean corpuscular volume (MCV), white blood cell count and differential, total lymphocyte count, platelet count Electrolytes: Sodium, potassium, chloride, calcium, phosphate, magnesium Liver function tests: AST (SGOT), ALT (SGPT), alkaline phosphatase, bilirubin, albumin, prealbumin, retinol-binding protein, prothrombin/INR Miscellaneous: BUN, creatinine, triglycerides, cholesterol, free fatty acids, ketones, uric acid, calcium, copper, zinc, magnesium, transferrin |
A complete history of current medications is essential to alert caregivers to potential underlying deficiencies and drug-nutrient interactions. Although rarely the sole cause of malnutrition, certain over-the-counter herbal preparations can alter nutrient absorption. Agents containing ephedra and caffeine may be abused to induce excessive weight loss. Ginkgo and other preparations enhance cytochrome p450 metabolism of various drugs. Information about socioeconomic factors and a detailed dietary history may uncover other risk factors.
A careful physical examination begins with an overall assessment of the patient’s appearance. Patients with severe malnutrition may appear frankly emaciated, but more subtle signs of malnutrition include temporal muscle wasting, skin pallor, edema, and generalized loss of body fat. Protein status is evaluated from the bulk and strength of the extremity muscles and visible evidence of temporal and thenar muscle wasting. Cardiac flow murmurs may result from anemia. Vitamin deficiencies may be indicated by changes in skin texture, the presence of follicular plugging or a skin rash, corneal vascularization, cracks at the corners of the mouth (cheilosis), hyperemia of the oral mucosa (glossitis), cardiac enlargement, altered sensation in the hands and feet, absence of vibration and position sense (dorsal and lateral column deficits), or abnormal quality and texture of the hair. Trace metal deficiencies produce cutaneous and neurologic abnormalities similar to those associated with vitamin deficiency and may cause changes in the mental status of the patient.
Anthropometric Measurements
Anthropometry is the science of assessing body size, weight, and proportions. Anthropometric measurements gauge body weight and composition with the intent of providing specific information about lean body mass and fat stores. Body composition studies may be used to determine total body water, fat, nitrogen, and potassium. Anthropometric measurements that can be easily performed in the clinic or at the bedside include determination of height and weight, with calculation of body mass index (BMI). Additional measurements such as arm span, body part summation, or knee-height measurement can also be used in nutrition assessment. More advanced techniques allow the clinician to assess the patient’s visceral and somatic protein mass and fat reserve. Accurate weight is important, as is current weight expressed as a percentage of ideal body weight. Ideal body weight values are taken from the 1983 Metropolitan Height-Weight Tables.
The BMI is used to measure protein-calorie malnutrition as well as overnutrition (eg, obesity). A BMI between 18.5 and 24.9 is considered normal in most Western civilizations. Overweight is defined as a BMI from 25 to 29.9, and a BMI greater than 30 defines obesity. BMI is calculated as follows:
Dual-energy x-ray absorptiometry (DEXA) is increasingly available in hospitals and can be used to assess various body compartments (mineral, fat, lean muscle mass). Most protein resides in skeletal muscle. Somatic (skeletal) protein reserve is estimated by measuring the mid-humeral circumference. This measurement is corrected to account for subcutaneous tissue, yielding the mid-humeral muscle circumference (MHMC). The result is compared with normal values for the patient’s age and gender to determine the extent of protein depletion. Fat reserve is commonly estimated from the thickness of the triceps skin fold (TSF). Reliability of anthropometric measurements is dependent on the skill of the person performing the measurement and is subject to error if performed by different caregivers on the same patient.
Laboratory Data
The visceral protein reserve is estimated from various serum protein levels, total lymphocyte count, and antigen skin testing (Table 10–2). The serum albumin level provides a rough estimate of the patient’s nutritional status but is a better prognostic indicator than tool for nutritional assessment. Serum albumin less than 3.5 mg/dL correlates with increased perioperative morbidity and mortality and increased length of hospital stay. Because albumin has a relatively long half-life (20 days), other serum proteins with shorter half-lives have greater utility for assessing response to nutritional repletion. Transferrin has a shorter half-life of 8-10 days and is a more sensitive indicator of adequate nutrition repletion than albumin. Prealbumin has a half-life of 2-3 days, and retinol-binding protein has a half-life of 12 hours. Unfortunately, their serum levels are also influenced by other factors, limiting their utility in assessing nutritional status or repletion.
Table 10–2. Staging of malnutrition.
Immune function may be assessed by hypersensitivity skin testing as well as total lymphocytic count, a reflection of T- and B-cell status. Subcutaneous injection of common antigens provides a semiobjective assessment of the antibody-mediated immune response, commonly impaired in malnourished patients. A low total lymphocyte count (TLC) correlates directly with the degree of malnutrition, though the count may be altered by infection, chemotherapy, and other factors, thus limiting its usefulness.
Nutritional Indices
Indices provide a means of risk-stratification and objective comparison among patients (Table 10–3). Additionally, many nutritional indices have been prospectively validated and can provide prognostic information to further guide nutrition support services. Along with the BMI, these indices can assist surgeons in determining the correct timing for intervention and the progress being made toward the goal of adequate nourishment.
Table 10–3. Nutritional indices.
Creatinine-height index (CHI) may be used to determine the degree of protein malnutrition, although it is less valid in patients who are severely catabolic or have chronic renal disease. A 24-hour urinary creatinine excretion is measured and compared with normal standards. CHI is calculated by the following equation:
The urinary excretion of 3-methylhistidine is a more precise measurement of lean body mass and associated protein stores. The amino acid histidine is irreversibly methylated in muscle. During protein turnover, 3-methylhistidine is not reutilized for synthesis, so the urinary excretion of this compound correlates well with muscle protein breakdown. Unfortunately, measurement of 3-methylhistidine is too expensive for use as a routine clinical test.
The prognostic nutrition index (PNI) has been validated in patients undergoing either major cancer or gastrointestinal surgery and found to accurately identify a subset of patients at increased risk for complications. Furthermore, preoperative nutritional repletion has been shown to reduce postoperative morbidity in this patient group. The PNI has been widely adapted to identify patients at risk in nonsurgical populations, who may benefit from nutritional support.
The nutrition risk index (NRI) was used by the VA TPN Cooperative Study Group for determining preoperative malnutrition, and it has since been prospectively cross-validated against other nutritional indices with good results. The index successfully stratifies perioperative morbidity and mortality using serum albumin and weight loss as predictors of malnutrition. Of note, the NRI is not a tool for tracking the adequacy of nutritional support, since supplemental nutrition often fails to improve serum albumin levels.
Subjective global assessment (SGA) is a clinical method that has been validated as reproducible and that encompasses the patient’s history and physical examination. It is based on five features of the medical history (weight loss in the past 6 months, dietary intake, gastrointestinal symptoms, functional status or energy level, and metabolic demands) along with four features of the physical examination (loss of subcutaneous fat, muscle wasting, edema, and ascites). Limitations of the SGA include its focus on chronic instead of acute nutritional changes and its enhanced specificity at the expense of sensitivity.
The mini-nutritional assessment (MNA) is a rapid and reliable tool for evaluating the nutritional status of the elderly. It is composed of 18 items and takes approximately 15 minutes to complete. The assessment includes an evaluation of a patient’s health, mobility, diet, anthropometrics, and a subject self-assessment. An MNA score of 24 or higher indicates no nutritional risk, while a score of 17-23 indicates a potential risk of malnutrition and a score of less than 17 indicates definitive malnutrition.
The malnutrition universal screening tool (MUST) detects protein-energy malnutrition and identifies individuals at risk of developing malnutrition using three independent criteria: current weight status, unintentional weight loss, and acute disease effect. The patient’s current body weight is determined by calculating the BMI (kg/m2). Weight loss (over the past 3-6 months) is determined by looking at the individual’s medical record. An acute disease factor is then included if the patient is currently affected by a pathophysiologic condition and there has been no nutritional intake for more than 5 days. A total score is calculated placing the patients in a low, medium, or high category for risk of malnutrition. A major advantage of this screening tool is its applicability to adults of all ages across all health care settings. Additionally, this method provides the user with management guidelines once an overall risk score has been determined. Studies have shown that MUST is quick and easy to use and has good concurrent validity with most other nutrition assessment tools tested.
The geriatric nutritional risk index (GNRI) is adapted from the NRI and is specifically designed to predict the risk of morbidity and mortality in hospitalized elderly patients. The GNRI is calculated using a formula incorporating both serum albumin and weight loss. After determining the GNRI score, patients are categorized into four grades of nutrition-related risk: major, moderate, low, and no risk. Finally, the GNRI scores are correlated with a severity score that takes into account nutritional status-related complications. The GNRI is not an index of malnutrition but rather a “nutrition-related” risk index.
The quickest and simplest measure of nutritional status is the instant nutritional assessment (INA). Serum albumin level and the TLC form the basis of this evaluation. Significant correlations between depressed levels of these parameters and morbidity and mortality have been noted. Not surprisingly, abnormalities of these same parameters are even more significant in critically ill patients. Although not designed to replace more extensive assessment measures, this technique allows for quick identification and early intervention in those individuals in greatest danger of developing complications of malnutrition.
Determining Energy Requirements
Adult basal energy expenditure (BEE) is calculated using a modification of the Harris-Benedict equation (Table 10–4). This calculation includes four variables: height (cm), weight (kg), gender, and age (y). Total energy expenditure (TEE) represents the caloric demands of the body under certain physiologic stresses. TEE is determined by multiplying BEE by a disease-specific stress factor. TEE should be used to guide nutritional supplementation.
Table 10–4. Total energy expenditure equation for adults.
Indirect calorimetry is the most accurate method for direct measurement of daily caloric requirements. Using a metabolic cart, oxygen consumption (o2) and carbon dioxide production (CO2) are directly measured from the patient’s pulmonary gas flow. Based on these measurements and the amount of nitrogen excreted in the urine, the resting energy expenditure (REE) can be derived using the Weir formula as follows:
REF (Kcal/min) = 3.9 (o2) + 1.1 (co2) − 2.2 (urine nitrogen)
where o2 and co2 are expressed in milliliters per minute and urine nitrogen is in grams per minute. The utility of this technique is limited by the expense and cumbersomeness of the metabolic cart.
The respiratory quotient (RQ) is the ratio of carbon dioxide production to oxygen consumption in the metabolism of fuels by the body. When the RQ is 1, pure carbohydrate is being oxidized. Patients metabolizing lipids only will have an RQ of 0.67. Lipogenesis occurs in patients with excess caloric intake (overfeeding). When excessive calories are ingested or administered, the RQ is greater than 1 and can theoretically approach 9. The excess production of CO2 may impair ventilator weaning in patients, particularly those with intrinsic lung disease (eg, chronic obstructive pulmonary disease).
NUTRIENT REQUIREMENTS & SUBSTRATES
The body requires an energy source to remain in steady state. About 50% of the basal metabolic rate (BMR) reflects the work of ion pumping, 30% represents protein turnover, and the remainder is expended on recycling of amino acids, glucose, lactate, and pyruvate. Total energy expenditure is the sum of energy consumed by basal metabolic processes, physical activity, the specific dynamic action of protein, and extra requirements resulting from injury, sepsis, or burns. Energy consumed in physical activity constitutes 10%-50% of the total in normal subjects but decreases to 10%-20% for hospitalized patients. Energy expenditure and requirements vary, depending on the illness or trauma. The increase in energy expenditure above basal needs is about 10% for elective operations, 10%-30% for trauma, 50%-80% for sepsis, and 100%-200% for burns (depending on the extent of the wound). Metabolic energy can be derived from carbohydrates, proteins, or fats.
Carbohydrate Metabolism
Carbohydrates are the body’s primary fuel source, accounting for 35% of total caloric intake. Each gram of enteric carbohydrate provides 4.0 kilocalories (kcal) of energy. Parenterally administered carbohydrates (eg, intravenous dextrose) yield 3.4 kcal/g.
Carbohydrate digestion is initiated by salivary amylase, and absorption occurs within the first 150 cm of the small intestine. Salivary and pancreatic amylases cleave starches into oligosaccharides. Surface oligosaccharidases then hydrolyze and transport these molecules across the gastrointestinal tract mucosa. Deficiencies in carbohydrate digestion and absorption are rare in surgical patients. Pancreatic amylase is abundant, and maldigestion of starch is unusual, even in patients with limited pancreatic exocrine function. Patients with diseases such as celiac sprue, Whipple disease, and hypogammaglobulinemia often have generalized intestinal mucosal flattening leading to oligosaccharidase deficiency and diminished carbohydrate uptake.
More than 75% of ingested carbohydrate is broken down and absorbed as glucose. Hyperglycemia stimulates insulin secretion from pancreatic β cells, which stimulates protein synthesis. Intake of 400 kcal of carbohydrate per day minimizes protein breakdown, particularly after adaptation to starvation. Cellular uptake of glucose, stimulated by insulin, inhibits lipolysis and promotes glycogen formation. Conversely, pancreatic glucagon is released in response to starvation or stress; it promotes proteolysis, glycogenolysis, lipolysis, and increased serum glucose. Glucose is vital for wound repair, but excessive carbohydrate intake or repletion with excessive amounts of glucose can cause hepatic steatosis and neutrophil dysfunction.
Protein Metabolism
Proteins are composed of amino acids, and protein metabolism produces 4.0 kcal/g. Digestion of proteins yields single amino acids and dipeptides, which are actively absorbed by the gastrointestinal tract. Gastric pepsin initiates digestion. Pancreatic proteases, activated by enterokinase in the duodenum, are the principal effectors of protein degradation. Once digested, half of protein absorption occurs in the duodenum, and complete protein absorption is achieved by the mid-jejunum.
Protein absorption occurs efficiently throughout the small intestine; therefore, protein malabsorption is relatively infrequent even after extensive intestinal resection. Protein balance reflects the sum of protein synthesis and degradation. Because protein turnover is dynamic, the published requirements for protein, amino acids, and nitrogen are only approximations.
Total body protein in a 70-kg person is approximately 10 kg, predominantly in skeletal muscle. Daily protein turnover is 300 g, or roughly 3% of total body protein. The daily protein requirement in healthy adults is 0.8 g/kg body weight. In the United States, the typical daily intake averages twice this amount. Protein synthesis or breakdown can be determined by measuring the nitrogen balance (Table 10–5). Protein intake of 6.25 g is equivalent to 1 g of nitrogen. Nitrogen intake is the sum of nitrogen delivered from enteric and parenteral feeding. Nitrogen output is the sum of nitrogen excreted in the urine and feces, plus losses from drainage (eg, exudative wounds, fistula). Urea nitrogen losses are determined from a 24-hour urine collection. Fecal nitrogen loss can be approximated by 1 g/d, and an additional 2-3 g/d of nonurea nitrogen loss occurs in the urine (eg, ammonia). The accuracy of nitrogen balance calculations can be improved through measurement over several weeks. When losses of nitrogen are large (eg, diarrhea, protein-losing enteropathy, fistula, or burn exudate), measurements of nitrogen balance lose accuracy because of the difficulty in collecting secretions for nitrogen measurement. Despite these shortcomings, 24-hour urine collection is the best practical means of measuring net protein synthesis and breakdown.
Table 10–5. Nitrogen balance.
The 20 amino acids are divided into essential amino acids (EAAs) and nonessential amino acids (NEAAs) depending on whether they can be synthesized de novo in the body. They are further divided into aromatic (AAAs), branched chain (BCAAs), and sulfur-containing amino acids. Only the L-isotype of an amino acid is utilized in human protein. Certain amino acids have unique metabolic functions, particularly during starvation or stress. Alanine and glutamine preserve carbon during starvation, and leucine stimulates protein synthesis and inhibits catabolism. Specific amino acids are addressed below.
As the respiratory fuel for enterocytes, glutamine plays an important role in the metabolically stressed patient. Following injury and other catabolic events, intracellular glutamine stores may decrease by over 50% and plasma levels by 25%. The decline of glutamine associated with injury or stress exceeds that of any other amino acid and persists during recovery after the concentrations of other amino acid have normalized. Supplementation with glutamine maintains intestinal cell integrity, villous height, and mucosal DNA activity and helps minimize reduction in numbers of T and B cells during stress.
Catabolic states are characterized by accelerated skeletal muscle proteolysis and translocation of amino acids from the periphery to the visceral organs. Glutamine accounts for a major portion of the amino acids released by muscle in these states. Intravenous supplementation with glutamine may improve neutrophil and macrophage function as well as decrease bacterial translocation across the intestinal mucosal barrier in burn and other critically ill patients. However, the utility of enteral supplementation remains controversial.
Arginine is a substrate for the urea cycle and nitric oxide production and a secretagogue for growth hormone, prolactin, and insulin. Arginine has been identified as the sole precursor of nitric oxide (endothelial-derived relaxing factor). The effects of arginine on T cells may be very important in maintaining the gut barrier. Formulas supplemented with arginine have been shown to improve nitrogen balance and wound healing, promote T-cell proliferation, enhance neutrophil phagocytosis, and reduce production of inflammatory mediators and infectious complications.
Lipid Metabolism
Lipids comprise 25%-45% of caloric intake in the typical diet. Each gram of lipid provides 9.0 kcal of energy. The introduction of fat to the duodenum results in secretion of cholecystokinin and secretin, leading to gallbladder contraction and pancreatic enzyme release. Reabsorption of bile salts in the terminal ileum (eg, the enterohepatic circulation) is necessary to maintain the bile salt pool. The liver is able to compensate for moderate intestinal bile salt losses by increased synthesis from cholesterol. Ileal resection may lead to depletion of the bile salt pool and subsequent fat malabsorption. Lipolysis is stimulated by steroids, catecholamines, and glucagon but is inhibited by insulin.
The body can synthesize fats from other dietary substrates, but two of the long-chain fatty acids (linoleic and linolenic) are essential. Insufficient intake of these essential fats leads to fatty acid deficiency and can be prevented by supplying a minimum of 3% of the total caloric intake as essential fatty acids.
The polyunsaturated fatty acids (PUFAs) are grouped into two families: ω-6 and ω-3 fatty acids. Linoleic acid is an example of the ω-6 PUFAs; ω-linolenic acid of the ω-3 PUFAs. Both linoleic and linolenic acid can be processed into arachidonic acid, a precursor in the synthesis of eicosanoids.
Eicosanoids are potent biochemical mediators of cell-to-cell communication and are involved in inflammation, infection, tissue injury, and immune system modulation. They also modulate numerous events involving cell-mediated and humoral immunity and can be synthesized in varying amounts by immune cells, particularly macrophages and monocytes.
Medium-chain fatty acids are not components of most oral diets but are widely used in enteral tube feedings. They are easily digested, absorbed, and oxidized and are not precursors to the inflammatory or immunosuppressive eicosanoids. Short-chain fatty acids, such as butyrate and to a lesser extent propionate, are utilized by colonocytes and provide up to 70% of their energy requirements. Since butyrate is not synthesized endogenously, the colonic mucosa relies on intraluminal bacterial fermentation to obtain this fuel.
Nucleotides, Vitamins, & Trace Elements
In addition to the principal sources of metabolic energy (calories), many other substances are necessary to ensure adequate nutrition. Nucleotides are recognized as an important nutritional substrate in critically ill patients. Vitamins are essential for normal metabolism, wound healing, and immune function, and cannot be synthesized de novo. The normal requirements for vitamins are shown in Table 10–6. Vitamin requirements may increase acutely in illness. Trace elements are integral cofactors for many enzymatic reactions and are generally not stored by the body in excess of requirements.
Table 10–6. Daily electrolyte, trace element, vitamin, and mineral requirements for adults.
Nucleic acids are precursors of DNA and RNA and are not normally considered essential for human growth and development. The need for dietary nucleotides increases in severe stress and critical illness. Nucleotides are formed from purines and pyrimidines, and their abundance is especially important for rapidly dividing cells such as enterocytes and immune cells. Immunosuppression has been reported in renal transplant patients being maintained on nucleotide-free diets. Dietary nucleotides are necessary for helper-inducer T-lymphocyte activity. Diets supplemented with RNA or the pyrimidine uracil have been shown to restore delayed hypersensitivity and augment both the lymphoproliferative response and IL-2 receptor expression. Nucleotides may facilitate recovery from infection. These substrates are often incorporated into enteral formulas as potential immunomodulators.
Vitamins A, D, E, and K are fat soluble and are absorbed in the proximal small bowel in association with bile salt micelles and fatty acids. After absorption, they are delivered to the tissues in chylomicrons and stored in the liver (vitamins A and K) or subcutaneous tissue and skin (vitamins D and E). Although rare, there are reports of toxicity from excessive intake of fat-soluble vitamins (eg, hypervitaminosis A from consuming polar bear liver). Fat-soluble vitamins participate in immune function and wound healing. For example, intake of vitamin A 25,000 IU daily counteracts steroid-induced inhibition of wound healing, largely through increases in TBG-β.
Vitamins B1, B2, B6, and B12, vitamin C, niacin, folate, biotin, and pantothenic acid are absorbed in the duodenum and proximal small bowel, transported in portal vein blood, and utilized in the liver and peripherally. Water-soluble vitamins serve as cofactors to facilitate reactions involved in the generation and transfer of energy and in amino acid and nucleic acid metabolism. Water-soluble vitamins have limited storage in the body. Because of their limited storage, water-soluble vitamin deficiencies are relatively common.
The daily requirements for the trace elements (Table 10–6) vary geographically depending on differences in soil composition. There are currently nine identified essential trace minerals (Fe, Zn, Cu, Se, Mn, I, Mb, Cr, Co). Trace elements have important functions in metabolism, immunology, and wound healing. Subclinical trace element deficiencies occur commonly in hospitalized patients and various disease states.
Iron serves as the core of the heme prosthetic group in hemoglobin and in the mitochondrial cytochrome respiratory process. Impaired cerebral, muscular, and immunologic function can occur in patients with iron deficiency before anemia becomes clinically evident. Particular attention should be paid to assessing iron stores in pregnant and lactating women.
Zinc deficiency is characterized by a perioral pustular rash, darkening of skin creases, neuritis, cutaneous anergy, hair loss, and alterations in taste and smell. Copper deficiency is manifested by microcytic anemia (unresponsive to iron), defective keratinization, or pancytopenia. Chromium deficiency presents as glucose intolerance during prolonged parenteral nutrition administration without evidence of sepsis. Selenium deficiency, which can occur in patients receiving parenteral nutrition for a prolonged period, is manifested by proximal neuromuscular weakness or cardiac failure with electrocardiographic changes. Manganese deficiency is associated with weight loss, altered hair pigmentation, nausea, and low plasma levels of phospholipids and triglycerides. Molybdenum deficiency results in elevated plasma methionine levels and depressed uric acid concentrations, producing a syndrome consisting of nausea, vomiting, tachycardia, and central nervous system disturbances.
Iodine is a key component of thyroid hormone. Deficiency is rare in the United States because of the use of iodinated salt. Chronically malnourished patients can become iodine-deficient. Since thyroxine participates in the neuroendocrine response to trauma and sepsis, iodine should be included in parenteral nutrition solutions.
NUTRITIONAL PATHOPHYSIOLOGY
Physiologic processes, immunocompetence, wound healing, and recovery from critical illness all depend upon adequate nutrient intake. A working knowledge of nutritional pathophysiology is essential in planning nutritional regimens.
Starvation
During an overnight fast, liver glycogen is rapidly depleted after a fall in insulin and parallel rise in plasma glucagon levels (Figure 10–1). Carbohydrate stores are depleted after a 24-hour fast. In the first few days of starvation, caloric needs are met by fat and protein degradation. There is an increase in hepatic gluconeogenesis from amino acids derived from the breakdown of muscle protein. Hepatic glucose production must satisfy the energy demands of the hematopoietic and the central nervous systems, particularly the brain, which is dependent on glucose oxidation during acute starvation. The release of amino acids from muscle is regulated by insulin, which signals hepatic amino acid uptake, polyribosome formation, and protein synthesis. The periodic rise and fall of insulin associated with ingestion of nutrients stimulates muscle protein synthesis and breakdown. During starvation, chronically depressed insulin levels result in a net loss of amino acids from muscle. Protein synthesis drops while protein catabolism remains unchanged. Hepatic gluconeogenesis requires energy, which is supplied by the oxidation of unesterified free fatty acid (FFA). The fall in insulin along with a rise in plasma glucagon levels leads to an increase in the concentration of cyclic adenosine monophosphate (cAMP) in adipose tissue, stimulating hormone-sensitive lipase to hydrolyze triglycerides and release FFA. Gluconeogenesis and FFA mobilization require the presence of ambient cortisol and thyroid hormone (a permissive effect).
Figure 10–1. The plasma substrate concentrations and hormone levels following an overnight fast. The brain is dependent on glucose, which is supplied predominantly by hepatic glycogenolysis until glycogen supplies are exhausted.
During starvation, the body attempts to conserve energy substrate by recycling metabolic intermediates. The hematopoietic system utilizes glucose anaerobically, leading to lactate production. Lactate is recycled back to glucose in the liver via the glucogenic (not gluconeogenic) Cori cycle (Figure 10–2). The glycerol released during peripheral triglyceride hydrolysis is converted into glucose via gluconeogenesis. Alanine and glutamine are the preferred substrates for hepatic gluconeogenesis from amino acids and contribute 75% of the amino acid–derived carbon for glucose production.
Figure 10–2. The cycles that preserve metabolic intermediates during fasting. Lactate is recycled to glucose via the Cori cycle, while pyruvate is transaminated to alanine in skeletal muscle and converted to glucose by hepatic gluconeogenesis.
BCAAs are unique because they are secreted rather than taken up by the liver during starvation; they are oxidized by skeletal and cardiac muscle to supply a portion of the energy requirements of these tissues; and they stimulate protein synthesis and inhibit catabolism. The amino groups derived from oxidation of BCAAs or transamination of other amino acids are donated to pyruvate or α-ketoglutarate to form alanine and glutamine. Glutamine is taken up by the small bowel, transaminated to form additional alanine, and released into the portal circulation. Along with glucose, these amino acids participate in the glucose-alanine/glutamine-BCAA cycle, which shuttles amino groups and carbon from muscle to liver for conversion into glucose.
Gluconeogenesis from amino acids results in a urinary nitrogen excretion of 8-12 g/d, predominantly as urea, which is equivalent to a loss of 340 g/d of lean tissue. At this rate, 35% of the lean body mass would be lost in 1 month, a uniformly fatal amount. However, starvation can be survived for 2-3 months as long as water is available. The body adapts to prolonged starvation by decreasing energy expenditures and shifting the substrate preference of the brain to ketones (Figure 10–3). After roughly 10 days of starvation, the brain adapts to use lipid as its primary fuel in the form of ketones. The BMR decreases by slowing the heart rate and reducing stroke work, while voluntary activity declines owing to weakness and fatigue. The RQ, which in early starvation is 0.85 (reflecting mixed carbohydrate and fat oxidation), falls to 0.70, indicating near-exclusive fatty acid utilization. Blood ketone levels rise sharply, accompanied by increased cerebral ketone oxidation. Brain glucose utilization drops from 140 g to 60-80 g/d, decreasing the demand for gluconeogenesis. Ketones also inhibit hepatic gluconeogenesis, and urinary nitrogen excretion falls to 2-3 g/d. The main component of urine nitrogen is now ammonia (rather than urea), derived from renal transamination and gluconeogenesis from glutamine, and it buffers the acid urine that results from ketonuria. Acute or chronic starvation is characterized by hormone and fuel alterations orchestrated by changing blood substrate levels and can be conceptualized as a “substrate-driven” process. In summary, the adaptive changes in uncomplicated starvation are a decrease in energy expenditure (as much as a 30% reduction), a change in type of fuel consumed to maximize caloric potential, and preservation of protein.
Figure 10–3. The metabolic adaptation to chronic starvation whereby the brain shifts its substrate preference to ketones produced by the liver. Hepatic gluconeogenesis falls and protein breakdown is diminished, thus conserving lean tissue.
Elective Operation or Trauma
The metabolic effects of both surgical procedures and trauma (Figure 10–4) differ from those of starvation due to neurohormonal activation, accelerating the loss of lean tissue and inhibiting metabolic adaptation of starvation. Following injury, neural impulses stimulate the hypothalamus. Norepinephrine is released from sympathetic nerve endings, epinephrine from the adrenal medulla, aldosterone from the adrenal cortex, antidiuretic hormone (ADH) from the posterior pituitary, insulin and glucagon from the pancreas, and corticotropin, thyrotropin, and growth hormone from the anterior pituitary. This results in elevation of serum cortisol, thyroid hormone, and somatomedins. The effects of the heightened neuroendocrine secretion include peripheral lipolysis from activation of lipase by glucagon, epinephrine, cortisol, and thyroid hormone; accelerated catabolism, with a rise in proteolysis stimulated by cortisol; decreased peripheral glucose uptake due to insulin antagonism by growth hormone and epinephrine.
Figure 10–4. The metabolic response to trauma is a result of neuroendocrine stimulation, which accelerates protein breakdown, stimulates gluconeogenesis, and produces glucose intolerance.
These effects result in a rise in plasma FFA, glycerol, glucose, lactate, and amino acids. The liver subsequently increases glucose production, as a result of glucagon-stimulated glycogenolysis and enhanced gluconeogenesis induced by cortisol and glucagon.
Accelerated glucose production, along with inhibited peripheral uptake, produces the glucose intolerance commonly observed in traumatized patients. The kidney retains water and sodium due to increases in ADH and aldosterone. Urinary nitrogen excretion increases up to 15-20 g/d following severe trauma, equivalent to a daily lean tissue loss of 750 g. Without exogenous nutrients, the median survival under these circumstances is only 15 days.
In contrast to the substrate dependency of uncomplicated starvation, elective surgical procedures and trauma are “neuroendocrine-driven” processes. In contrast, however, metabolic responses observed following elective procedures are vastly different from those following major trauma. During general anesthesia, the neuroendocrine response is blunted in the operating room through the use of analgesics and immobilization. Sedated patients lack cortical stimulation to the hypothalamus. Careful intraoperative handling of tissues reduces proinflammatory cytokine release. The net result is that the REE rises only 10% in postoperative patients, compared with up to 30% following severe injury or trauma.
Sepsis
The metabolic changes during sepsis differ from those observed after acute injury (Figure 10–5). The REE may increase by 50%-80%, and urinary nitrogen excretion can reach up to 30 g/d, predominantly due to profound muscle catabolism and impaired synthesis. Catabolism at this rate results in a median survival of 10 days without nutritional input. The plasma glucose, amino acid, and FFA levels increase more than with trauma. Hepatic protein synthesis is stimulated, with both enhanced secretion of export protein and accumulation of structural protein. The RQ falls to near 0.7, indicative of lipid oxidation. Lipolysis and gluconeogenesis continue despite supplementation with carbohydrate or fat, leading to the hyperglycemia and insulin resistance commonly observed in septic patients.
Figure 10–5. During sepsis, cytokines (IL-1, IL-2, TNF) released by lymphocytes and macrophages contribute to catabolism of muscle and adipose tissue and amplify the neurohormonal response to antecedent trauma.
Sepsis results in elaboration of inflammatory cytokines, most notably TNF-α, IL-1, and IL-6. Alteration in hepatic protein synthesis toward production of acute-phase proteins is triggered by IL-6. Septic patients also develop an abnormal plasma amino acid pattern (increased levels of AAAs and decreased levels of BCAAs). In contrast to simple starvation, protein conservation does not occur in sepsis. Terminal sepsis results in further increases in plasma amino acids and a fall in glucose concentration, as hepatic amino acid clearance declines and gluconeogenesis ceases.
ENTERAL NUTRITIONAL THERAPY
Enteral Versus Parenteral Nutrition
Enteral nutritional support is safer and less expensive than parenteral nutrition and has the added benefit of preserving gut functionality. Prospective, randomized trials have demonstrated the superiority of enteral nutrition in reducing postoperative complications and length of hospital stay. “Feeding the gut” also results in fewer septic complications. Parenteral nutrition has a role in the management of surgical patients, but utilizing the gastrointestinal tract should remain the preferred treatment option. Enteral supplementation is not risk-free; physicians must know how to prevent and treat the complications associated with enteral feedings to ensure safe and successful administration.
Benefits of Enteral Feeding
The gastrointestinal tract can be used for administration of complex nutrients, such as intact protein, peptides, and fiber, that cannot be given intravenously. Gut processing of intact nutrients provides a stimulus for hepatic synthetic function of proteins, whereas administration of nutrients directly into the systemic circulation bypasses the portal circulation. In addition to its systemic benefits, enteral feeding has beneficial local effects on gastrointestinal mucosa. These include trophic stimulation and maintenance of absorptive structures by nourishing the enterocytes directly, thus supporting epithelial cell repair and replication. Luminal nutrients such as glutamine and short-chain fatty acids are used as fuel by the cells of the small bowel and colon, respectively.
The presence of food in the gut, particularly complex proteins and fats, triggers feeding-dependent neuroendocrine activity. This activity stimulates the transport of immunoglobulins into the gut, particularly secretory immunoglobulin A, which is important for preventing bacterial adherence to gut mucosa and bacterial translocation. Enteral feeds also prevent villus atrophy, minimizing subsequent loss of epithelial border function and help to maintain normal gut pH and flora, diminishing opportunistic bacterial overgrowth in the small bowel. In recent animal studies enteral nutrition has been shown to reverse the aberrant cytokine profile associated with parenteral nutrition that is believed to lead to enterocyte apoptosis.
Enteral feeding is generally considered safer than parenteral feeding. Systematic review of randomized trials involving critically ill adults has demonstrated fewer infectious complications with enteral nutrition compared with parenteral nutrition; however there was no significant difference in mortality. Hyperglycemia, and its resulting inhibition of neutrophil-mediated immunity, also occurs more frequently with parenteral feeding. Enteral nutrition has its own potential complications (discussed shortly).
The direct costs of enteral feeding are generally less than those with parenteral nutrition. Direct costs include formula, feeding pumps, and tube placement. The cost advantage for enteral feeding is even greater when indirect costs such as central line placement, infection or thrombosis, and home health care are considered.
Indications for Enteral Feeding
Enteral nutrition is the preferred method of nutrition support for malnourished patients or those at risk for developing malnutrition and who have an intact gastrointestinal tract. Patients who are either unable or unwilling to eat to meet their daily needs are candidates for enteral support. Factors influencing the timing of initiation of enteral nutrition include evidence of preexisting malnutrition, expected degree of catabolic activity, duration of the current illness, and anticipated return to intake by mouth. Patients with partially functioning gastrointestinal tracts (eg, short bowel syndrome, proximal enterocutaneous fistula) often can tolerate some enteral feeding but may require a combined regimen of both parenteral and enteral nutrition to meet total caloric needs.
Possible Contraindications to Enteral Feeding
Aside from complete bowel obstruction, contraindications to enteral feeding are relative or temporary rather than absolute. Patients with short bowel, gastrointestinal obstruction, gastrointestinal bleeding, protracted vomiting and diarrhea, fistulas, ileus, or active gastrointestinal ischemia may require a period of bowel rest. In times of physiologic stress, the body shunts blood away from the splanchnic circulation. Feeding a patient who is hemodynamically unstable or requires vasopressors may produce bowel ischemia in the setting of preexisting tenuous perfusion. The choice of an appropriate feeding site, administration technique, formula, and equipment may circumvent many of these contraindications.
Implementing Enteral Supplementation
Prepyloric access via nasogastric tube is beneficial because it is less expensive, easier to secure and maintain, and less labor-intensive than small bowel access. Contraindications to delivery in the stomach are delayed gastric emptying, gastric outlet obstruction, and a history of repeated aspiration of tube feedings due to reflux. Some physicians consider the inability to protect the airway (eg, in comatose patients) a relative contraindication to gastric feeding. Diabetics and patients with severe head injuries may have profound gastroparesis. Postpyloric access via a duodenal or jejunal nasoenteric tube is preferred when gastric feedings are not tolerated, when patients are at risk for reflux or aspiration, or when early enteral nutrition is desired. A new feeding tube, guided in place by an external magnet, may provide ease of bedside placement of postpyloric tubes. Although a number of bedside methods (eg, auscultation, feeding tube aspirate pH measurements, observation for patient coughing) have been described to check tube placement, these methods can be unreliable. Therefore, tube position below the diaphragm should always be confirmed radiographically before initiating enteral feeding.
Permanent gastrostomy or jejunostomy tubes may be inserted when long-term enteral feeding is indicated. Placement of a feeding tube at the time of the initial operation requires forethought, with consideration given to the patient’s expected postoperative course, anticipated ileus, and possible future need for supplementation (eg, during chemoradiation therapy).
Currently available dietary formulations for enteral feedings may be divided into polymeric commercial formulas, chemically defined formulas, and modular formulas (Table 10–7). Selection of the correct formulation is predicated on patient need, cost, availability, and institutional custom.
Table 10–7. Enteral formulas.
Nutritionally complete commercial formulas or standard enteral diets vary in protein, carbohydrate, and fat composition. Most formulas use sucrose or glucose as the carbohydrate source and are suitable for lactose-deficient patients. Commercial formulas are convenient, sterile, and affordable. They are recommended for patients experiencing minimal metabolic stress who have normal gut function.
Chemically defined formulas are commonly called elemental diets. The nutrients are provided in a predigested and readily absorbed form. They contain protein in the form of free amino acids or polypeptides. Amino acid (elemental) and polypeptide diets are efficiently absorbed in the presence of compromised gut function. However, they are more expensive than commercial formulas and are hyperosmolar, which may cause cramping, diarrhea, and fluid losses.
Modular formulations include special formulas used for specific clinical situations such as pulmonary, renal, or hepatic failure or immune dysfunction. The available preparations vary in (1) caloric and protein content; (2) protein, carbohydrate, and fat compositions; (3) nonprotein carbohydrate calorie-to-gram nitrogen ratio; (4) osmolality; (5) content of minor trace metals (selenium, chromium, and molybdenum); and (6) content of various amino acids (glutamine, glutamate, BCAAs).
In the past, elaborate protocols for initiating tube feedings were used. It is currently recommended that feedings be started with full-strength formula at a slow rate and steadily advanced. This approach reduces the risk of microbial contamination and achieves full nutrient intake earlier. Formulas are often introduced at full strength at 10-40 mL/h initially and advanced to the goal rate in increments of 10-20 mL/h every 4-8 hours as tolerated. Conservative initiation and advancement rates are recommended for patients who are critically ill, those who have not been fed for some time, and those who are receiving high-osmolality or calorie-dense formula. In such patients, starting feeding at 10 mL/h yields the trophic benefit of enteral feeds without unduly stressing the gut. In patients with active lifestyles, gastric feeds can be provided as boluses of up to 400 mL each, delivered at intervals of 4-6 hours.
Assessing gastrointestinal tolerance to enteral feeding includes monitoring for abdominal discomfort, nausea and vomiting, abdominal distention, and abnormal bowel sounds or stool patterns. Gastric residual volumes are used to evaluate gastric emptying of enteral feedings. High residuals raise concerns about intolerance to gastric feedings and the potential risk for regurgitation and aspiration. While differences in the recommended threshold for gastric residual volume vary, a residual greater than 200-250 mL or associated signs or symptoms of intolerance should prompt holding of tube feeds. If the abdominal examination is unremarkable, feedings should be postponed for at least an hour and the residual volume rechecked. If high residuals persist without associated clinical signs and symptoms, a promotility agent (eg, erythromycin, metoclopramide) may be added to the feeding regimen.
Complications of Enteral Feeding
Technical complications occur in about 5% of enterally fed patients and include clogging of the tube; esophageal, tracheal, bronchial, or duodenal perforation; and tracheobronchial intubation with tube feeding aspiration. Patients with decreased consciousness or impaired gag reflexes or those who have undergone endotracheal intubation are at increased risk for technical complications. The tip of the feeding tube must be positioned and verified radiographically. Other methods to evaluate tube placement are not consistently reliable. Generally, the wire stylet used for positioning should not be reinserted once removed. The incidence of tube clogging can be reduced by periodic water flushes and avoiding administration of syrup-based medications through the tube.
Functional complications occur in up to 25% of tube-fed patients and include nausea, vomiting, abdominal distention, constipation, and diarrhea. Feeding the small bowel instead of the stomach can diminish abdominal symptoms. In the critically injured patient, diarrhea is typically multifactorial; it results from polypharmacy (eg, multiple antibiotics), mechanical gut dysfunction (eg, partial small bowel obstruction), intestinal bacterial overgrowth (eg, Clostridium difficile), and protein content or osmolarity of the diet. Treatment consists of stopping any unnecessary medications, correcting gut dysfunction, changing enteral formulation (eg, intact protein vs amino acid or polypeptide formula), or reducing the osmolarity of the formula. In some circumstances, adding highly fermentable or viscous soluble fibers, such as guar gum, psyllium, pectin, or banana flakes have been shown to decrease diarrhea more than using fiber containing enteral formulas. Administering antidiarrheal agents can be beneficial after establishing that infection is not the source of diarrhea.
In the surgical population, C difficile is a common cause of diarrhea due to the routine use of perioperative antibiotics. The diagnosis of pseudomembranous colitis is confirmed by C difficile polymerase chain reaction or toxin assay, or sigmoidoscopy. The primary treatment is stopping unnecessary antibiotics. Additionally, either oral or intravenous metronidazole or vancomycin (oral or retention enema) can be started. Antimotility agents should be avoided.
Abnormalities in serum electrolytes, calcium, magnesium, and phosphorus can be minimized through vigilant monitoring. Hyperosmolarity (hypernatremia) may lead to mental lethargy or obtundation. The treatment of hypernatremia includes the administration of free water by giving either D5W intravenously or additional water flushes. Volume overload and subsequent congestive heart failure may occur as a result of excess sodium administration and is typically observed in patients with impaired ventricular function or valvular heart disease. Hyperglycemia may occur in any patient but is particularly common in individuals with preexisting diabetes or sepsis. The serum glucose level should be determined frequently and regular insulin administered accordingly.
PARENTERAL NUTRITION THERAPY
The development of parenteral nutritional support in the late 1960s revolutionized care of the surgical patient, particularly those with permanent inability to obtain adequate enteral nourishment. Despite its utility in select patients and circumstances, overuse of parenteral nutrition not only is costly but also poses unnecessary risk to patients. In general, parenteral nutrition should be employed only when the gastrointestinal tract cannot be utilized. Parenteral formulas usually deliver 75-150 nonprotein carbohydrate kcal/g of nitrogen infused, a ratio that maximizes carbohydrate and protein assimilation and minimizes metabolic complications (aminoaciduria, hyperglycemia, and hepatic glycogenesis). Nonenteral nutrition can be given as peripheral parenteral nutrition (PPN) or total parenteral nutrition (TPN) via a central line. In addition to route of administration, the two differ in (1) dextrose and amino acid content of the parenteral solution, (2) primary caloric source (glucose vs fat), (3) frequency of fat administration, (4) infusion schedule, and (5) potential complications.
Peripheral Parenteral Nutrition
Because peripheral parenteral nutrition (PPN) avoids the complications associated with central venous access, it is safer to administer than TPN. PPN is indicated for patients with compromised gut function who require supplemental nutrition for less than 14 days. It can be infused via an 18-gauge peripheral IV catheter or via a peripherally inserted central catheter (PICC line). Standard PPN therapy orders should include the administration schedule for the PPN solution and fat supplement, as well as explicit catheter care orders and monitoring guidelines.
The osmolarity of the PPN solution is limited to 900 mOsm to avoid phlebitis. Consequently, unacceptably large volumes of solution, greater than 2.5 L/d, are needed to fulfill the typical patient’s total nutritional requirements (Figure 10–6).
Figure 10–6. TPN therapy orders.
Total Parenteral Nutrition
Total parenteral nutrition (TPN) via a central line is indicated for patients who cannot obtain adequate nourishment via the gastrointestinal tract or, very rarely, in patients with severe preoperative undernutrition who cannot tolerate adequate enteral nutrition. A minimum duration of treatment of 7-10 days of adequate TPN is needed for preoperative nutritional repletion. Likewise, the use of postoperative TPN for only 2-3 days (eg, while awaiting return of bowel function) is discouraged, as the risks outweigh the benefits incurred over this short a period of time.
TPN is typically formulated for patients on the basis of their individual nutritional assessment. Most frequently, TPN is prepared in the pharmacy and provided as a 3-in-1 admixture of protein, carbohydrates, and fat. Alternatively, the lipid emulsion can be administered as a separate intravenous piggyback infusion. Other additives, vitamins, and trace minerals are added to TPN formulations as required (Table 10–8).
Table 10–8. TPN solution formulation.
The high osmolarity of TPN solutions necessitates administration via a central vein. The use of multilumen central venous catheters (CVCs) for TPN does not increase the risk of catheter infection; however, a port should be designated for exclusive use for TPN infusion to minimize handling of the line. CVC placement in the subclavian vein is ideal and well tolerated by the patient. Furthermore, the rate of catheter infection is lower for catheters placed in the subclavian compared to catheters placed in either the femoral or internal jugular vein. Femoral vein catheterization has the highest infectious rate and therefore should be avoided if possible. The CVC should be dressed with a sterile, dry gauze, and transparent (nonocclusive) dressing; a chlorhexidine gluconate impregnated sponge may be used as well.
If refeeding syndrome is suspected, the introduction of TPN should be gradual, with approximately 10 kcal/kg/d for the first 3 days. This amount is increased 15-20 kcal/kg/d for days 4-10. For all patients, additional maintenance IV fluids should be tapered or discontinued accordingly to maintain an even fluid balance.
Standard TPN therapy orders (Figure 10–6) should include the administration schedule for the TPN solution and fat supplement as well as explicit catheter care orders and monitoring guidelines (Figure 10–7). For active patients on long-term TPN, cycling the intravenous nutrition therapy over 8-16 hours at night allows freedom from the infusion pump during the remainder of the day.
Figure 10–7. TPN guidelines.
The TPN solution may be concentrated for patients who require fluid restriction (eg, those with pulmonary and cardiac failure). One liter of concentrated TPN solution usually contains a combination of D60W or D70W, 500 mL, and 10% or 15% amino acids, 500 mL, plus additives.
Patients in renal failure who cannot be dialyzed and who require fluid restriction should receive low-nitrogen TPN solution. Patients in renal failure who can undergo dialysis may receive the standard or high-nitrogen TPN formulations, with special attention directed toward minimizing potassium and phosphate intake.
COMPLICATIONS OF PARENTERAL NUTRITION
PPN Therapy
Technical complications of PPN are few. The most common problem is maintaining adequate venous access due to frequent incidence of phlebitis. The PPN infusion catheter must be moved frequently to other sites; therefore, prolonged PPN is rarely possible. Infectious complications such as catheter site skin infections and septic phlebitis develop in 5% of patients.
TPN Therapy
Complications resulting from parenteral nutrition can be broken down into those of a technical, infectious, and metabolic nature (Table 10–9). Many of the complications originate from the CVC, with more than 15% of patients developing some line-related complication. Other morbidity is attributable to line infection (typically bacterial) or metabolic abnormalities.
Table 10–9. Complications of nutritional therapy.
The risks of patient injury while placing a CVC are directly related to surgeon experience with the procedure. Arterial puncture (more common in internal jugular or femoral attempts) can occur in up to 10% of patients, while pneumothorax (predominantly during subclavian insertion) can develop in 2%-5%. The risk for injury increases dramatically after three failed insertion attempts at the same site.
Air embolism occurs when negative intrathoracic pressure draws air into a catheter or needle into a central vein. This is particularly serious in the presence of pulmonary-systemic shunts (eg, patients with a patent foramen ovale). It is characterized by sudden, severe respiratory distress, hypotension, and a cogwheel cardiac murmur. To reduce this risk, the patient should be placed in the Trendelenburg position (head down) during line insertion. When suspicion of air embolism is high, treatment involves placing the patient in the Durant position (Trendelenburg and left lateral decubitus) to direct the embolus to the apex of the right ventricle. Catheter-based aspiration can then be attempted.
The use of peripherally introduced central catheters (PICCs) allows peripherally initiated solutions to be delivered to the central venous system. They are well tolerated and easy to care for because of their location in an upper extremity. PICCs may be preferable to CVCs because of lower cost and fewer mechanical complications at placement.
Infection of the catheter exit site is frequently characterized by mild fever (37.5°-38°C), purulent discharge around the catheter, and erythema/tenderness of the surrounding skin. Late changes include induration of the skin and systemic sepsis. Local wound care and sterile dressing changes every 3 days can reduce site infection rates.
Primary line (catheter) infection can occur in up to 15% of patients with CVCs. Line infection should be strongly considered in any patient with a CVC who develops fever, new-onset glucose intolerance, leukocytosis, or positive blood cultures. There may be a slight increase in infectious risk with multilumen catheters. The use of antibiotic-impregnated catheters has been shown to significantly reduce nosocomial bloodstream infections. As noted previously, insertion in the subclavian vein reduces the risk of infection. The most common offending organisms are skin flora (Staphylococcus aureus, Staphylococcus epidermidis), although gram-negative rods can also colonize an indwelling catheter. Table 10–10 depicts one treatment algorithm for treating suspected CVC infections. With documented positive blood cultures or more than 15 colony-forming units on catheter cultures, the catheter should be removed and a line holiday attempted with peripheral access. Insertion of a new CVC can then be performed at a separate site once bacteremia has resolved. Antibiotics should be started empirically in patients with sepsis.
Table 10–10. Complications of TPN.
The refeeding syndrome was first described in prisoners freed from concentration camps after World War II. Similar pathophysiology may develop when initiating TPN in patients with severe malnutrition and weight loss (> 30% of their usual weight). In starvation, energy is derived principally from fat metabolism. TPN results in a shift from fat to glucose as the predominant fuel, and rapid anabolism increases the production of phosphorylated intermediates of glycolysis. These intermediates trap phosphate, producing profound hypophosphatemia. Hypokalemia and hypomagnesemia also occur. The lack of phosphate and potassium lead to a relative adenosine triphosphate (ATP) deficiency, resulting in the insidious onset of respiratory failure and reduced cardiac stroke volume. Because of these risks, the rate of TPN administration in a severely malnourished patient should be slowly increased over several days. Twice-daily monitoring of electrolytes is also indicated, with repletion as appropriate.
Hepatic dysfunction is a common manifestation of long-term parenteral nutrition support. The exact etiology is unclear; however, in part it is related to the initial bypassing of the portal circulation when providing intravenous nutrition. Severe hepatic steatosis may progress to cirrhosis. Acalculous cholecystitis can also occur in these patients, likely from biliary stasis and lack of gallbladder contraction. Patients on TPN need weekly liver function tests and lipid panels.
Home Nutrition Support
Patients requiring home nutrition support (HNS) present clinical challenges different from those in an acute care setting. Route of enteral or parenteral administration must be based on length of therapy, frequency of use, and caregiver/patient ability. Regular physical examinations and frequent laboratory monitoring (Figure 10–8) should continue as long as patients remain on HNS therapy. Home care services must be established prior to discharge and are vital to the success of these patients.
Figure 10–8. Laboratory monitoring form for home nutrition support (HNS).
For patients requiring home parenteral nutrition, weekly laboratory monitoring continues until electrolytes stabilize. Once stable, laboratory values can often be checked on a monthly basis, and changes can be made to the TPN formula as needed. Electrolyte and hepatic enzymes must be followed to monitor for metabolic derangements and end-organ damage. Parenteral nutrition–associated liver disease is the most devastating complication of long-term parenteral nutrition therapy. Early clinical intervention with a combination of nutritional, medical, hormonal, and surgical therapies is potentially effective in preventing liver disease progression. However, as progression is frequently subtle, it is often not recognized until liver injury is irreversible. Although parenteral nutrition–associated liver failure is hypothesized to be multifactorial in origin, the etiology is poorly understood. When end-stage liver disease (ESLD) develops in these patients, multiorgan transplantation (liver and small bowel) is generally required.
DIETS
Optimal Diet
The optimal diet should have the following distribution of energy sources: carbohydrate 55%-60%, fat 30%, and protein 10%-15%. Refined sugar should constitute less than 15% of dietary energy and saturated fats no more than 10%, the latter balanced by 10% monounsaturated and 10% polyunsaturated fats. Cholesterol intake should be limited to about 300 mg/d (one egg yolk contains 250 mg of cholesterol). The amount of salt in the average American diet, 10-18 g daily, far exceeds the recommended 3 g/d. For Western societies to meet the criteria for an optimal diet, consumption of fat must decrease (from 40%) and consumption of complex carbohydrate should increase. Meat is presently overemphasized as a protein source, at the expense of grain, legumes, and nuts. Diets that include substantial fish intake have been associated with a decrease in mortality from cardiovascular disease and are attributed to high concentrations of ω-3 fatty acids, principally eicosapentaenoic and docosahexaenoic acids.
Many adults, particularly those who do not drink milk, consume inadequate amounts of calcium. In women this may result in calcium deficiency and skeletal calcium depletion, predisposing women to osteoporosis and axial bony fractures. “Fiber” is the generic term for a chemically complex group of indigestible carbohydrate polymers, including cellulose, hemicellulose, lignins, pectins, gums, and mucilages. The amount of fiber in Western diets averages 25 g/d, but some people ingest as little as 10 g daily. Those who consume low-fiber diets are more likely to develop chronic constipation, appendicitis, diverticular disease, and possibly diabetes mellitus and colonic neoplasms. Bran cereals and bread, fruit, potatoes, rice, and leafy vegetables are rich sources of fiber.
Regular Diets
Many concepts regarding diets are archaic and based on currently unaccepted views of illness. For example, the utility of a low-residue diet in diverticular disease is questionable. The “progressive diet,” designed for postoperative feeding and consisting of a clear liquid (high in sodium), then a full liquid (high in sucrose), then a regular diet, is based on outmoded concepts. When peristalsis returns after operation, as evidenced by bowel sounds and ability to tolerate water, most patients are able to ingest a regular diet. Regular diets have an unrestricted spectrum of foods and are most attractive to the patient. An average regular hospital diet for 1 day contains 95-110 g of protein, with a total caloric content of 1800-2100 kcal. This composition reflects the nutritional needs of healthy persons of average height and weight and will not meet the increased demands imposed by malnutrition or disease.
Lactose Intolerance & Lactose-Free Diets
A lactose-free diet is indicated for patients who have symptoms such as diarrhea, bloating, or flatulence after the ingestion of milk or milk products. Lactose intolerance is genetically determined and occurs in 5%-10% of European Caucasians, 60% of Ashkenazi Jews, and 70% of African Americans. Subclinical lactose intolerance may become unmasked following surgery on gastrointestinal tract (eg, gastrectomy). Similarly, avoidance of lactose-containing products is often beneficial advice for patients with Crohn disease, ulcerative colitis, and AIDS. The efficiency of lactose digestion and absorption can be measured by giving 100 g of oral lactose, then measuring the blood glucose concentration at 30-minute intervals over 2 hours. Patients with lactose intolerance exhibit a rise in blood glucose of 20 mg/dL or less. A lactose-free diet may be deficient in calcium, vitamin D, and riboflavin.
Postgastric Bypass Diet
The popularity of gastric bypass surgery for weight loss continues to increase. The diet changes that must occur to ensure safe and appropriate weight loss are quite specific after surgery. Immediately after surgery, only small amounts of liquids (eg, 30 mL q3h) should be consumed. After tolerance of liquids is established, pureed foods should be consumed for the 4 weeks after surgery. Food should be consumed as very small meals and snacks throughout the day. Choosing a variety of foods, avoiding concentrated sweets, and consuming adequate protein are essential to the success of these patients. Protein supplements are often required to ensure adequate protein consumption postoperatively. Particularly with gastric bypass procedures, patients are prone to deficiencies of the fat-soluble vitamins (A, D, E, and K), calcium, iron, vitamin B12, and folate necessitating the indefinite supplementation of daily multivitamins.
DISEASE-SPECIFIC NUTRITION SUPPORT
Burns
Thermal injury has a tremendous impact on metabolism because of prolonged, intense neuroendocrine stimulation. Extensive burns can double or triple the REE and urinary nitrogen losses, producing a nitrogen loss of 20-25 g/m2 TBSA/d. If left unattended, lethal cachexia becomes imminent in less than 30 days. The increase in metabolic demands following thermal injury is proportional to the extent of ungrafted body surface. The principal mediators of burn hypermetabolism are catecholamines, corticosteroids, and inflammatory cytokines, which return to baseline only after skin coverage is complete. Decreasing the intensity of neuroendocrine stimulation by providing adequate analgesia and a thermoneutral environment lowers the accelerated metabolic rate and helps to decrease catabolic protein loss until the burned surface can be grafted. Burned patients are prone to infection, and the cytokines activated by sepsis further augment catabolism.
Because infection often complicates the clinical course of patients with burn injury, and infectious complications are more likely with parenteral nutrition, the enteral route of feeding is preferred whenever tolerated. Enteral feeding may be started within the first 6-12 hours post burn to attenuate the hypermetabolic response and improve postburn survival. Gastric ileus can be avoided through the use of a nasojejunal tube.
Patients with burns have increased caloric requirements. In addition to estimated maintenance needs (females, 22 kcal/kg/d; males, 25 kcal/kg/d), these patients require an additional 40 kcal per percentage point of burned total body surface area (TBSA). A 70-kg man with 40% TBSA burns would require 48 kcal/kg/d. Protein requirements are also markedly increased from the normal 0.8 g/kg/d to approximately 1.5-2.5 g/kg/d in severely burned patients. Of course, these are initial estimates, and periodic reassessment of nutritional status (eg, prealbumin levels, nitrogen balance) is required in these patients. During the hypermetabolic phase of burn injury (0-14 days), the ability to metabolize fat is restricted, so a diet that derives calories primarily from carbohydrate is preferable. Following the hypermetabolic phase, the metabolism of fat becomes normal. The burn patient should also be given supplemental arginine, nucleotides, and ω-3 polyunsaturated fat to stimulate and maintain immunocompetence.
Diabetes
Glucose intolerance often complicates nutritional supplementation, particularly with parenteral administration. Complications associated with TPN administration occur more frequently during prolonged hyperglycemia. Unopposed glycosuria may lead to osmotic diuresis, loss of electrolytes in the urine, and possibly nonketotic coma. Significant controversy exists, but the preponderance of available evidence suggests that intensive insulin therapy, as compared with standard therapy, does not provide an overall survival benefit, but instead may increase mortality, and is associated with a higher incidence of hypoglycemia. Factors that may aggravate hyperglycemia include the use of corticosteroids, certain vasopressors (eg, epinephrine), preexisting diabetes mellitus, and occult infection.
Maintaining normoglycemia in injured or postoperative patients may be challenging. Serial serum glucose levels should be monitored regularly. If hyperglycemia does not occur, these measurements can be obtained less frequently once the nutritional goal is reached. Patients may require subcutaneous insulin administered on a sliding scale or continuous intravenous insulin infusions to control their hyperglycemia. For patients who do not require an insulin infusion, the previous day’s insulin total from a sliding scale may be determined and half to two-thirds of that amount added to the next TPN order to provide a more uniform administration.
Cancer
Cancer is the second leading cause of death in the United States, and over two-thirds of patients with cancer will develop nutritional depletion and weight loss at some time during the course of the illness. Malnutrition and its sequelae are the direct cause of death in 20% of these patients. Weight loss is an ominous presenting sign in many malignancies. Furthermore, antineoplastic treatments, such as chemotherapy, radiation therapy, or operative extirpation, can worsen preexisting malnutrition. Cancer cachexia manifests as progressive involuntary weight loss, fatigue, anemia, wasting, and tissue depletion. It may occur at any stage of the disease. Nutrition support has become an essential adjunct in caring for the cancer patient.
Many studies have evaluated the effectiveness of nutrition support in patients with cancer, with varying results. Increasing efforts have been directed toward the use of enteral rather than parenteral nutrition because it is simpler, presumably safer, and less costly. Nutritional supplementation in cancer patients may reduce infectious complications or perioperative morbidity, but convincing evidence of improvement in overall survival is lacking.
Patients with cancer may have altered energy expenditure and abnormalities of protein and carbohydrate metabolism. REE increases by 20%-30% in certain malignant tumors. The increases in REE can occur even in patients with extreme cachexia in whom a similar degree of uncomplicated starvation would produce profound decreases in REE. Changes in carbohydrate metabolism consist of impaired glucose tolerance, elevated glucose turnover rates, and enhanced Cori cycle activity. Owing to the high rate of anaerobic glucose metabolism in neoplastic tissue, patients with extensive tumors are susceptible to lactic acidosis when given large glucose loads during TPN. These patients also exhibit increased lipolysis, elevated FFA and glycerol turnover, and hyperlipidemia.
Patients with cancer avidly retain nitrogen despite losses in most lean tissue. Animal carcass analysis has shown that the retained nitrogen resides in the tumor, which behaves as a nitrogen trap. Synthesis, catabolism, and turnover of body protein are all increased, but the change in catabolism is greatest.
The utility of enteral supplementation with immune-enhancing agents is unclear. These substances include arginine, glutamine, essential fatty acids, RNA, and BCAAs. Several studies have attempted to examine outcomes in patients with cancer who are fed with enteral formulas supplemented with immune-enhancing agents, compared to routine enteral feeding alone. The findings were summarized by Zhang and coworkers. Meta-analysis of 19 studies with a total of 2231 cancer patients demonstrated a significant decrease in overall postoperative infection complication risk, noninfection complication risk, and hospital stay when perioperative immunonutrition was compared to standard diet. Exactly which elements confer these benefits remains unknown.
Renal Failure
Whether nutritional support improves the outcome from acute renal failure is difficult to determine because of the metabolic complexities of the disease. Patients with acute renal failure may have normal or increased metabolic rates. Renal failure precipitated by x-ray contrast agents, antibiotics, aortic or cardiac surgery, or periods of hypotension is associated with a normal or slightly elevated REE and a moderately negative nitrogen balance (4-8 g/d). When renal failure follows severe trauma, rhabdomyolysis, or sepsis, the REE may be markedly increased and the nitrogen balance sharply negative (15-25 g/d). When dialysis is frequent, losses into the dialysate of amino acids, vitamins, glucose, trace metals, and lipotrophic factors can be substantial.
Patients in renal failure (serum creatinine over 2 mg/dL) with a normal metabolic rate who cannot undergo dialysis should receive a concentrated (minimal volume) enteral or parenteral diet containing protein, fat, dextrose, and limited amounts of sodium, potassium, magnesium, and phosphate.
Hepatic Failure
Most patients with hepatic failure present with acute decompensation superimposed on chronic hepatic insufficiency. Typically, a history of poor dietary intake contributes to the chronic depletion of protein, vitamins, and trace elements. Water-soluble vitamins, including folate, ascorbic acid, niacin, thiamin, and riboflavin, are especially likely to be deficient. Fat-soluble vitamin deficiency may be a result of malabsorption due to bile acid insufficiency (vitamins A, D, K, and E), deficient storage (vitamin A), inefficient utilization (vitamin K), or failure of conversion to active metabolites (vitamin D). Hepatic iron stores may be depleted either from poor intake or as a result of gastrointestinal blood loss. Total body zinc is decreased owing to the above factors plus increased urinary excretion.
The use of BCAA-enriched amino acid formulations for TPN in patients with liver disease is controversial because the results of controlled trials are inconclusive. The efficacy of BCAA-enriched amino acid formulations for TPN in patients with hepatic encephalopathy has been studied in numerous controlled trials that had contradicting results. Meta-analysis of these studies demonstrated an improvement in mental state by the BCAA-enriched solutions, however there was no definite benefit in survival. Therefore, patients with hepatic failure should receive a concentrated enteral or parenteral diet with reduced carbohydrate content, a combination of EFAs and other lipids, a standard mixture of amino acids, and limited amounts of sodium and potassium.
Cardiopulmonary Disease
Malnutrition is associated with myocardial dysfunction, particularly in the late stages, and fatal cardiac failure can develop in extreme cachexia. Cardiac muscle uses FAAs and BCAAs as preferred metabolic fuels instead of glucose. During starvation, the heart rate slows, cardiac size decreases, and the stroke volume and cardiac output decrease. As starvation progresses, cardiac failure ensues, along with chamber enlargement and anasarca.
The profound nutritional depletion that may accompany chronic heart failure, particularly in valvular disease, results from anorexia of chronic disease, passive congestion of the liver, malabsorption due to venous engorgement of the small bowel mucosa, and enhanced peripheral proteolysis due to chronic neuroendocrine secretion. Attempts at aggressive nutritional repletion in patients with cardiac cachexia have produced inconclusive results. Concentrated dextrose and amino acid preparations should be used to avoid fluid overload. Nitrogen balance should be measured to ensure adequate nitrogen intake. Lipid emulsions must be administered cautiously because they can produce myocardial ischemia and negative inotropy. Feeding these patients with either enteral or parenteral nutrition should be undertaken cautiously to avoid refeeding syndrome and hypophosphatemia.
Patients with severe chronic obstructive pulmonary disease may have difficulty weaning from the ventilator if they are overfed. This relates to the RQ, a measure of oxygen consumption and carbon dioxide production by the body in metabolism. An RQ of 1 reflects pure carbohydrate utilization, while an RQ greater than 1 occurs during lipogenesis (energy storage). Although normal lungs can tolerate increased CO2 production (RQ > 1) without adversely affecting respiration, patients with chronic obstructive pulmonary disease may experience CO2 retention and inability to wean. The treatment is to increase the percentage of calories delivered as lipid and to avoid overfeeding at all costs.
Disease of the Gastrointestinal Tract
Benign gastrointestinal disease (eg, inflammatory bowel disease, fistula, pancreatitis) often leads to nutritional problems due to intestinal obstruction, malabsorption, or anorexia. Chronic involvement of the ileum in inflammatory bowel disease produces malabsorption of fat- and water-soluble vitamins, calcium and magnesium, anions (phosphate), and the trace elements iron, zinc, chromium, and selenium. Protein-losing enteropathy, accentuated by transmural destruction of lymphatics, can add to protein depletion. Treatment with sulfasalazine can produce folate deficiency, and glucocorticoid administration may accelerate breakdown of lean tissue and enhance glucose intolerance owing to stimulation of gluconeogenesis. Patients with inflammatory bowel disease who require elective surgery should be evaluated for malnutrition preoperatively.
Patients with gastrointestinal fistulas can develop electrolyte, protein, fat, vitamin, and trace metal deficiencies; dehydration; and acid-base imbalance. Aggressive fluid replacement is often needed. Patients with fistulas often require nutritional support. The choice of feeding route or formula will depend on the level and length of dysfunctional bowel. Patients with proximal enterocutaneous fistulas (from the stomach to the mid-ileum) should receive TPN with no oral intake. Patients with low fistulas should receive TPN initially, but after infection is brought under control, they can often be switched to an enteral formula or even a low-residue diet.
Pancreatitis
The concept of pancreatic rest has evolved over the recent years. Ranson criteria can serve as a rough estimate of the need for nutritional support. Patients with acute pancreatitis who present with three or fewer Ranson criteria should be treated with fluid replacement, pain control, and brief bowel rest. Most of these patients can rapidly resume an oral diet and do not benefit from TPN. Those with more than three Ranson criteria should receive nutritional support. Recent data documents the successful use of enteral diets, particularly elemental products via jejunal access, avoiding TPN if feasible.
Short Bowel Syndrome
Inadequate intestinal absorptive surface leads to malabsorption, excessive water loss, electrolyte derangements, and malnutrition. The absorptive capacity of the small intestine is highly redundant, and resection of up to half its functional length is reasonably well tolerated. Short bowel syndrome typically occurs when less than 200 cm of anatomic small bowel remain, although the presence of the ileocecal valve may reduce this length to 150 cm. However, short bowel syndrome also may occur from functional abnormalities of the small bowel resulting from severe inflammation or motility disorder. The optimal nutritional therapy for a patient with short bowel syndrome must be tailored individually and depends upon the underlying disease process and the remaining anatomy. Following resection, the remaining bowel undergoes long-term adaptation, with observed increases in villous height, luminal diameter, and mucosal thickness. The estimated minimum length of small bowel required for adult patients to become independent of TPN is 120 cm.
Adaptation to short gut occurs over time, and initial management should be directed at avoiding electrolyte imbalance and dehydration while providing daily caloric requirements through TPN. Some patients may eventually supplement TPN with oral intake. In these patients, dietary management includes consuming frequent small meals, avoiding hyperosmolar foods, restricting fat intake, and limiting consumption of foods high in oxalate (precipitates nephrolithiasis).
AIDS
Patients with AIDS frequently develop protein-calorie malnutrition and weight loss. Many factors contribute to deficiencies of electrolytes (sodium and potassium), trace metals (copper, zinc, and selenium), and vitamins (A, C, E, pyridoxine, and folate). Enteropathy may impair fluid and nutrient absorption and produce a voluminous, life-threatening diarrhea. Dehydration and further immune dysfunction occur as a consequence of refractory diarrhea.
Malnourished AIDS patients require a daily intake of 35-40 kcal and 2.0-2.5 g protein. Those with normal gut function should be given a high-protein, high-calorie, low-fat, lactose-free oral diet. Patients with compromised gut function require an enteral (amino acid or polypeptide) or parenteral nutrition.
Solid Organ Transplant Recipients
Patients who have undergone organ transplantation present unique issues in relation to nutritional management due to both the preexisting disease state and the medications taken to prevent graft rejection. During the acute posttransplant phase, adequate nutrition is required to help prevent infection, promote wound healing, support metabolic demands, replenish lost stores, and mediate the immune response. Organ transplantation complications, including rejection, infection, wound healing, renal insufficiency, hyperglycemia, and surgical complications, require specific nutritional requirements and therapies.
Obesity is associated with both decreased patient survival and decreased graft survival, in part due to a greater incidence of surgical, metabolic, and cardiovascular complications. Patients with BMI greater than 30 kg/m2 show a higher incidence of steroid-induced posttransplant diabetes mellitus. The first 6 weeks following transplantation is characterized by increased nutritional demands due to a combination of surgical metabolic stress and high doses of immunosuppressive medications. Daily protein intake recommendation in the immediate posttransplant phase, as well as during acute rejection episodes, is 1.5 g/kg actual body weight.
Long-term immunosuppression is associated with protein hypercatabolism, obesity, dyslipidemia, glucose intolerance, hypertension, hyperkalemia, and alteration of vitamin D metabolism. Approximately 60% of renal recipients develop dyslipidemia posttransplant. Alterations in lipid metabolism may be associated with corticosteroids, cyclosporine, thiazide diuretics, or beta-blockers, as well as with renal insufficiency, nephrotic syndrome, insulin resistance, or obesity. There is evidence that abnormal lipoprotein levels lead to glomerulosclerosis, renal disease progression, and even potential graft failure.
Dietary salt restriction is recommended in transplant patients, as salt intake may play a role in cyclosporine-induced hypertension caused by sodium retention. Sodium intake is recommended not to exceed 3 g/d. Cyclosporine is associated with hypomagnesemia and hyperkalemia, especially during the immediate posttransplant phase when the dosage is high. Additionally, antihypertensive treatment with beta-blocker agents or with angiotensin-converting enzyme (ACE) inhibitors may exacerbate hyperkalemia. Calcium, phosphorus, and vitamin D metabolism are influenced by prolonged therapy with steroids leading to osteopenia and osteonecrosis. The daily recommendation for dietary calcium is 800-1500 mg, and the recommended intake of phosphorus is 1200-1500 mg/d. Some patients may also require supplementation of active vitamin D. Patients on a low-protein diet often need multivitamin supplements. During the first year, the major nutritional goal is to treat preexisting malnutrition and prevent excessive weight gain.
Major Trauma
In severely injured patients, metabolic changes must be acknowledged early and monitored during the posttraumatic phase. Severe trauma induces alteration of metabolic pathways and activation of the immune system. Depending on the severity of the initial injury, catabolic changes in posttraumatic metabolism can last from several days to weeks. The posttraumatic metabolic changes include hypermetabolism with increased energy expenditure, enhanced protein catabolism, insulin resistance associated with hyperglycemia, failure to tolerate glucose load, and high plasma insulin levels (“traumatic diabetes”). As a general rule, the metabolic demands of the patient can increase by 1.3-1.5 times the normal requirements.
After the state of traumatic-hemorrhagic shock has been compensated for, metabolic changes are characterized by an increased metabolic turnover, activation of the immune system, and induction of the hepatic acute-phase response. This results in increased consumption of energy and oxygen. In addition to the acute hypermetabolic state, the systemic inflammatory cascade is initiated, with the release of proinflammatory cytokines and activation of the complement system. Bacterial translocation from the gut may further aggravate these metabolic sequelae and inflammatory response.
Many severely injured patients require inotropic support, and vasoactive drugs promote catabolism by reducing serum levels of anabolic hormones. In contrast, endogenous catecholamines, cortisol, and glucagon levels are elevated after trauma, leading to increased energy substrate mobilization. Proteinolysis of skeletal muscle and glycolysis are increased to provide the substrates for hepatic gluconeogenesis and biosynthesis of acute-phase proteins. The equilibrium is shifted toward supporting the immune response and wound healing at the cost of enhanced proteinolysis of skeletal muscle. In addition, stimulation of the neuroendocrine axis through stress, pain, inflammation, and shock increases the caloric turnover significantly above baseline. This leads to increased serum levels of catabolic hormones, such as cortisol, glucagon, and catecholamines, and decreased levels of insulin.
Appropriate immunonutrition should be started in the ICU, preferably by enteral route, in order to counteract the effects of the hypermetabolic state after major trauma. Without absolute contraindications, guidelines clearly favor the concept of early enteral nutrition within 24-48 hours after admission in the ICU. It is important not to overfeed critically injured patients with calories, since this may contribute to adverse outcomes. Early overfeeding of severely injured patients leads to an increase in oxygen consumption, carbon dioxide production, lipogenesis, and hyperglycemia and contributes to secondary immune suppression.
Obese patients are particularly susceptible to the adverse effects of overfeeding. Current feeding recommendations for morbidly obese ICU patients are a high protein, hypocaloric diet. Caloric provision should approximate 60%-70% of caloric requirements determined by indirect calorimetry or other predictive equation. A simplistic weight-based approach approximates 22-25 kcal and 2-2.5 g of protein per kg ideal body weight per day.
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