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.
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 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.
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.
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.
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.
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.
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).
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.
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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