Current Medical Diagnosis & Treatment 2015

29

Nutritional Disorders

Robert B. Baron, MD, MS

PROTEIN–ENERGY MALNUTRITION

 ESSENTIALS OF DIAGNOSIS

 Decreased intake of energy or protein, increased nutrient losses, or increased nutrient requirements.

 Kwashiorkor: caused by protein deficiency.

 Marasmus: caused by combined protein and energy deficiency.

 Protein loss correlates with weight loss: 35–40% total body weight loss is usually fatal.

 General Considerations

Protein–energy malnutrition occurs as a result of a relative or absolute deficiency of energy and protein. It may be primary, due to inadequate food intake, or secondary, as a result of other illness. For most developing nations, primary protein–energy malnutrition remains among the most significant health problems. Protein–energy malnutrition has been described as two distinct syndromes. Kwashiorkor,caused by a deficiency of protein in the presence of adequate energy, is typically seen in weaning infants at the birth of a sibling in areas where foods containing protein are insufficiently abundant.Marasmus, caused by combined protein and energy deficiency, is most commonly seen where adequate quantities of food are not available.

In industrialized societies, protein–energy malnutrition is most often secondary to other diseases. Kwashiorkor-like secondary protein–energy malnutrition occurs primarily in association with hypermetabolic acute illnesses such as trauma, burns, and sepsis. Marasmus-like secondary protein–energy malnutrition typically results from chronic diseases such as chronic obstructive pulmonary disease (COPD), heart failure, cancer, or AIDS. These syndromes have been estimated to be present in at least 20% of hospitalized patients. A substantially greater number of patients have risk factors that could result in these syndromes. In both syndromes, protein–energy malnutrition is caused either by decreased intake of energy and protein, increased nutrient losses, or increased nutrient requirements dictated by the underlying illness. For example, diminished oral intake may result from poor dentition or various gastrointestinal disorders. Loss of nutrients results from malabsorption and diarrhea as well as from glycosuria. Nutrient requirements are increased by fever, surgery, neoplasia, and burns.

 Clinical Findings

The clinical manifestations of protein–energy malnutrition range from mild growth retardation and weight loss to a number of distinct clinical syndromes. Children in the developing world manifest marasmus and kwashiorkor. In secondary protein–energy malnutrition as seen in industrialized nations, clinical manifestations are affected by the degree of protein and energy deficiency, the underlying illness that resulted in the deficiency, and the patient’s nutritional status prior to illness.

Progressive wasting that begins with weight loss and proceeds to more severe cachexia typically develops in most patients with marasmus-like secondary protein–energy malnutrition. In the most severe form of this disorder, most body fat stores disappear and muscle mass decreases, most noticeably in the temporalis and interosseous muscles. Laboratory studies may be unremarkable—serum albumin, for example, may be normal or slightly decreased, rarely decreasing to < 2.8 g/dL (< 28 g/L). In contrast, owing to its rapidity of onset, kwashiorkor-like secondary protein–energy malnutrition may develop in patients with normal subcutaneous fat and muscle mass or, if the patient is obese, in patients with excess fat and muscle. The serum protein level, however, typically declines and the serum albumin is often < 2.8 g/dL (< 28 g/L). Dependent edema, ascites, or anasarca may develop. As with primary protein–energy malnutrition, combinations of the marasmus-like and kwashiorkor-like syndromes can occur simultaneously, typically in patients with progressive chronic disease in whom a superimposed acute illness develops.

 Treatment

The treatment of severe protein–energy malnutrition is a slow process requiring great care. Initial efforts should be directed at correcting fluid and electrolyte abnormalities and infections. Of particular concern are depletion of potassium, magnesium, and calcium and acid–base abnormalities. The second phase of treatment is directed at repletion of protein, energy, and micronutrients. Treatment is started with modest quantities of protein and calories calculated according to the patient’s actual body weight. Adult patients are given 1 g/kg of protein and 30 kcal/kg of calories. Concomitant administration of vitamins and minerals is obligatory. Either the enteral or parenteral route can be used, although the former is preferable. Enteral fat and lactose are withheld initially. Patients with less severe protein–calorie undernutrition can be given calories and protein simultaneously with the correction of fluid and electrolyte abnormalities. Similar quantities of protein and calories are recommended for initial treatment.

Patients treated for protein–energy malnutrition require close follow-up. In adults, both calories and protein are advanced as tolerated, adults to 1.5 g/kg/d of protein and 40 kcal/kg/d of calories.

Patients who are re-fed too rapidly may develop a number of untoward clinical sequelae. During refeeding, circulating potassium, magnesium, phosphorus, and glucose move intracellularly and can result in low serum levels of each. The administration of water and sodium with carbohydrate refeeding can result in heart failure in persons with depressed cardiac function. Enteral refeeding can lead to malabsorption and diarrhea due to abnormalities in the gastrointestinal tract.

Refeeding edema is a benign condition to be differentiated from heart failure. Changes in renal sodium reabsorption and poor skin and blood vessel integrity result in the development of dependent edema without other signs of heart disease. Treatment includes reassurance, elevation of the dependent area, and modest sodium restriction. Diuretics are usually ineffective, may aggravate electrolyte deficiencies, and should not be used.

The prevention and early detection of protein–energy malnutrition in hospitalized patients require awareness of its risk factors and early symptoms and signs. Patients at risk require formal assessment of nutritional status and close observation of dietary intake, body weight, and nutritional requirements during the hospital stay.

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Raynaud-Simon A et al. Clinical practice guidelines from the French Health High Authority: nutritional support strategy in protein-energy malnutrition in the elderly. Clin Nutr. 2011 Jun;30(3):312–9. [PMID: 21251732]

White JV et al. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet. 2012 May;112(5):730–8. Erratum in: J Acad Nutr Diet. 2012 Nov;112(11):1899. [PMID: 22709779]

OBESITY

 ESSENTIALS OF DIAGNOSIS

 Excess adipose tissue; body mass index (BMI) > 30.

 Upper body obesity (abdomen and flank) of greater health consequence than lower body obesity (buttocks and thighs).

 Associated with health consequences, including diabetes mellitus, hypertension, and hyperlipidemia.

 General Considerations

Obesity is one of the most common disorders in medical practice and among the most frustrating and difficult to manage. Little progress has been made in prevention or treatment, yet major changes have occurred in our understanding of its causes and its implications for health.

 Definition & Measurement

Obesity is defined as an excess of adipose tissue. Accurate quantification of body fat requires sophisticated techniques not usually available in clinical practice. Physical examination is usually sufficient to detect excess body fat. More quantitative evaluation is performed by calculating the BMI.

The BMI closely correlates with excess adipose tissue. It is calculated by dividing measured body weight in kilograms by the height in meters squared.

The National Institutes of Health (NIH) define a normal BMI as 18.5–24.9. Overweight is defined as BMI = 25–29.9. Class I obesity is 30–34.9, class II obesity is 35–39.9, and class III (extreme) obesity is BMI > 40. Factors other than total weight, however, are also important. Upper body obesity (excess fat around the waist and flank) is a greater health hazard than lower body obesity (fat in the thighs and buttocks). Obese patients with increased abdominal circumference (> 102 cm in men and 88 cm in women) or with high waist–hip ratios (> 1.0 in men and > 0.85 in women) have a greater risk of diabetes mellitus, stroke, coronary artery disease, and early death than equally obese patients with lower ratios. Further differentiation of the location of excess fat suggests that visceral fat within the abdominal cavity is more hazardous to health than subcutaneous fat around the abdomen.

Current U.S. survey data demonstrate that 68% of Americans are overweight and 33.8% are obese. Women in the United States are more apt to be obese than men, and African-American and Mexican-American women are more obese than whites. The poor are more obese than the rich regardless of race. Approximately 60% of individuals with obesity in the United States have the metabolic syndrome (including three or more of the following factors: elevated abdominal circumference, blood pressure, blood triglycerides, and fasting blood sugar, and low high-density lipoprotein [HDL] cholesterol).

 Etiology

Obesity has been considered to be the direct result of a sedentary lifestyle plus chronic ingestion of excess calories. Although these factors are undoubtedly the principal cause in many cases, as much as 40–70% of obesity may be explained by genetic influences. Twin studies demonstrate substantial genetic influences on BMI with little influence from the childhood environment.

Five genes affecting control of appetite have been identified in mice. Mutations of each gene result in obesity, and each has a human homolog. One gene codes for a protein expressed by adipose tissue—leptin—and another for the leptin receptor in the brain. The other three genes affect brain pathways downstream from the leptin receptor. Numerous other candidate genes for human obesity have been identified. Only a small percentage (4–6%) of human obesity is thought to be due to single gene mutations. Most human obesity undoubtedly develops from the interactions of multiple genes, environmental factors, and behavior. The rapid increase in obesity in the last several decades clearly points to a major role of environmental factors in the development of obesity. Cross-sectional studies associate obesity with changes in gut flora. It is unknown whether altered gut flora contributes to the development of obesity or whether obesity changes the gut flora.

 Medical Evaluation of the Obese Patient

Historical information should be obtained about age at onset, recent weight changes, family history of obesity, occupational history, eating and exercise behavior, cigarette and alcohol use, previous weight loss experience, and psychosocial factors including assessment for depression and eating disorders. Particular attention should be directed at use of laxatives, diuretics, hormones, nutritional supplements, and over-the-counter medications.

Physical examination should assess the BMI, the degree and distribution of body fat, overall nutritional status, and signs of secondary causes of obesity.

Less than 1% of obese patients have an identifiable secondary, nonpsychiatric, cause of obesity. Hypothyroidism and Cushing syndrome are important examples that can usually be diagnosed by physical examination in patients with unexplained recent weight gain. Such patients require further endocrinologic evaluation, including serum thyroid-stimulating hormone (TSH) determination and dexamethasone suppression testing (see Chapter 26).

All obese patients should be assessed for medical consequences of their obesity by screening for the metabolic syndrome. Blood pressure, waist circumference, fasting glucose, low-density lipoprotein (LDL) and HDL cholesterol, and triglycerides should be measured.

 Treatment

Using conventional dietary techniques, only 20% of patients will lose 20 lb and maintain the loss for over 2 years; 5% will maintain a 40-lb loss. Average weight loss is approximately 7% of baseline weight. Continued close provider–patient contact appears to be more important for success of treatment than the specific features of any given treatment regimen. Careful patient selection will improve success rates and decrease frustration of both patients and therapists. Only sufficiently motivated patients should enteractive treatment programs. Specific attempts to identify motivated patients—eg, requesting a 3-day diet record—are often useful.

Most successful programs employ a multidisciplinary approach to weight loss, with hypocaloric diets, behavior modification to change eating behavior, aerobic exercise, and social support. Emphasis must be on maintenance of weight loss.

Dietary instructions for most patients incorporate the same principles that apply to healthy people who are not obese. This is achieved by emphasizing intake of a wide variety of predominantly “unprocessed” foods. Special attention is usually paid to limiting foods that provide large amounts of calories without other nutrients, ie, fat, sucrose, and alcohol. There is no physiologic advantage to diets that restrict carbohydrates, advocate relatively larger amounts of protein or fats, or recommend ingestion of foods one at a time. Diets that are restricted in carbohydrates (such as the Atkins and South Beach diets), however, can be effective in achieving a lower total calorie intake. Several studies have demonstrated that low-carbohydrate diets can be used safely and effectively for weight loss without adverse effects on lipids or other metabolic parameters. Meal replacement diets can also be used effectively and safely to achieve weight loss.

Long-term changes in eating behavior are required to maintain weight loss. Although formal behavior modification programs are available to which patients can be referred, the clinician caring for obese patients can teach a number of useful behavioral techniques. The most important technique is to emphasize planning and record keeping. Patients can be taught to plan menus and exercise sessions and to record their actual behavior. Record keeping not only aids in behavioral change, but also helps the provider to make specific suggestions for problem solving. Patients can be taught to recognize “eating cues” (emotional, situational, etc) and how to avoid or control them. Regular self-monitoring of weight is also associated with improved long-term weight maintenance.

Exercise offers a number of advantages to patients trying to lose weight and keep it off. Aerobic exercise directly increases the daily energy expenditure and is particularly useful for long-term weight maintenance. Exercise will also preserve lean body mass and partially prevent the decrease in basal energy expenditure (BEE) seen with semistarvation. When compared with no treatment, exercise alone results in small amounts of weight loss. Exercise plus diet results in greater weight loss than diet alone. A greater intensity of exercise is associated with a greater amount of weight loss. Up to 1 hour of moderate exercise per day is associated with long-term weight maintenance in individuals who have successfully lost weight. Social support is essential for a successful weight loss program. Continued close contact with clinicians and involvement of the family and peer group are useful techniques for reinforcing behavioral change and preventing social isolation.

Patients with severe obesity may require more aggressive treatment regimens. Very-low-calorie diets (≥ 800 kcal/d) result in rapid weight loss and marked initial improvement in obesity-related metabolic complications. Patients are commonly maintained on such programs for 4–6 months. Patients who adhere to the program lose an average of 2 lb per week. Average maximum weight loss is approximately 15% of initial weight. Most programs use meal replacement diets to achieve the very-low-calorie intake. Long-term weight maintenance following meal replacement programs is less predictable and requires concurrent behavior modification, long-term use of low-calorie diets, careful self-monitoring, and regular exercise. Side effects such as fatigue, orthostatic hypotension, cold intolerance, and fluid and electrolyte disorders are observed in proportion to the degree of calorie reduction and require regular supervision by a clinician. Other less common complications include gout, gallbladder disease, and cardiac arrhythmias. Although weight loss is more rapidly achieved with very-low-calorie diets as compared with traditional diets, long-term outcomes are equivalent.

Medications for the treatment of obesity are available both over the counter and by prescription. Considerable controversy exists as to the appropriate use of medications for obesity. NIH clinical obesity guidelines state that obesity drugs may be used as part of a comprehensive weight loss program for patients with BMI > 30 or those with BMI > 27 with obesity-related risk factors. There are few data, however, to suggest that medications can improve long-term outcomes associated with obesity.

Several medications are approved by the US Food and Drug Administration (FDA) for treatment of obesity. Catecholaminergic medications (eg, phentermine, diethylpropion, benzphetamine, and phendimetrazine) are approved for short-term use only and have limited utility. Orlistat works in the gastrointestinal tract rather than the central nervous system. By inhibiting intestinal lipase, orlistat reduces fat absorption. As expected, orlistat may result in diarrhea, gas, and cramping and perhaps also reduced absorption of fat-soluble vitamins. In randomized trials with up to 2 years of follow-up, orlistat has resulted in 2–4 kg greater weight loss than placebo. Orlistat (120 mg orally up to three times daily with each fat-containing meal) is approved for longer-term treatment of obesity in the United States. A lower dose formulation (Alli 60 mg, one capsule orally up to three times daily with each fat-containing meal; maximum of three capsules per day) is available without a prescription. Long-term clinical benefits have not been demonstrated. Although orlistat results in some additional weight loss at the end of 1- and 2-year clinical trials and, in some studies, improved obesity-related metabolic parameters, a beneficial impact on obesity-related clinical outcomes has not been established.

Additional medications approved for use in the United States are lorcaserin and the fixed combination of phentermine and topiramate. Lorcaserin is a selective serotonin receptor agonist. It is associated with modest weight loss, about 3% of initial weight more than placebo. Approximately twice as many patients (38% vs 16%) lose > 5% of initial weight on the medication compared to placebo. Post-marketing surveillance will focus on concerns of increased breast tumors in animal studies, increased valvular heart disease in earlier drugs of this class, and psychiatric side effects. The combination ofphentermine and topiramate, two older medications, results in dose-dependent weight loss. In clinical trials, patients receiving the lowest dose lost 7.8% more weight than those receiving placebo; with the higher dose, 9.8% more weight was lost. Common side effects include mood changes, fatigue, and insomnia. Since the medications increase heart rate, a large clinical trial to assess cardiovascular risk is being conducted. The medication is also associated with increased birth defects and should not be used during pregnancy.

Several additional medications and combinations of existing medications are also being investigated. Bupropion and naltrexone resulted in short-term weight loss but has not been approved due to ongoing concerns of increased cardiovascular risk. A clinical trial is in progress to further assess safety. Bupropion and zonisamide, exenatide and other incretins, and cetilistat (another pancreatic lipase inhibitor) are all being investigated.

One important weight loss medication, sibutramine, was removed from the market in the United States due to an increase in cardiovascular events in participants in a large randomized trial. This finding emphasizes the need to study the long-term effects of all weight loss medications on important clinical outcomes.

Bariatric surgery is an increasingly prevalent treatment option for patients with severe obesity. In the United States, gastric operations are considered the procedures of choice. Most popular is the Roux-en-Y gastric bypass (RYGB). In most centers, the operation can be done laparoscopically. RYGB typically results in substantial amounts of weight loss—over 30% of initial body weight in some studies. Complications occur in up to 40% of persons undergoing RYGB surgery and include peritonitis due to anastomotic leak; abdominal wall hernias; staple line disruption; gallstones; neuropathy; marginal ulcers; stomal stenosis; wound infections; thromboembolic disease; gastrointestinal symptoms; and nutritional deficiencies, including iron, vitamin B12, folate, calcium, and vitamin D. Operative mortality rates within 30 days are nil to 1% in low-risk populations but have been reported to be substantially higher in Medicare beneficiaries. One-year mortality rates have been reported as high as 7.5% in men with Medicare. The surgical volume (the number of cases performed by the surgeon or hospital) has been demonstrated to be an important predictor of outcome. Another operation is gastric banding. Gastric banding results in less dramatic weight loss than RYGB and has fewer short-term complications. Frequent follow-up, however, is required to adjust the gastric band. Longer-term follow-up has shown a 39% rate of major complications and a 60% rate of re-operation. A third operation, sleeve gastrectomy, is gaining in popularity. With this procedure, approximately three-quarters of the stomach is resected, but the gastrointestinal tract is otherwise left intact. Weight loss results are somewhat less than RYGB but greater than gastric banding.

NIH consensus panel recommendations are to limit obesity surgery to patients with BMIs over 40, or over 35 if obesity-related comorbidities are present. The procedure is cost-effective for patients with severe obesity and most third-party payers cover the procedure in selected patients. A large Swedish study suggested that bariatric surgery is associated with a significant reduction in deaths at 11-year follow-up. The number needed to treat to prevent one death in 11 years was 77 operations. A US Veterans Administration study, however, did not show a mortality benefit.

 When to Refer

Patients with BMI over 40 (or over 35 with obesity-related morbidities) who are interested in considering weight loss surgery.

Baretić M. Targets for medical therapy in obesity. Dig Dis. 2012;30(2):168–72. [PMID: 22722433]

Baron RB. Telling patients they are overweight or obese: an insult or an effective intervention? Arch Intern Med. 2011 Feb 28;171(4):321–2. [PMID: 21357808]

Derosa G et al. Anti-obesity drugs: a review about their effects and their safety. Expert Opin Drug Saf. 2012 May;11(3):459–71. [PMID: 22439841]

Flegal KM et al. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010 Jan 20;303(3):235–41. [PMID: 20071471]

Foster GD et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med. 2010 Aug 3;153(3):147–57. [PMID: 20679559]

Gray LJ et al. A systematic review and mixed treatment comparison of pharmacological interventions for the treatment of obesity. Obes Rev. 2012 Jun;13(6):483–98. [PMID: 22288431]

James WP et al; SCOUT Investigators. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010 Sep 2;363(10):905–17. [PMID: 20818901]

Jensen MD et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013 Nov 12. [Epub ahead of print] [PMID: 24222017]

Karlsson F et al. Assessing the human gut microbiota in metabolic diseases. Diabetes. 2013 Oct;62(10):3341–9. [PMID: 24065795]

Maciejewski ML et al. Cost-effectiveness of bariatric surgery. JAMA. 2013 Aug 21;310(7):742–3. [PMID: 23989885]

McCarthy M. US obesity rates are leveling out, but long term effects raise concern. BMJ. 2013 Aug 20;347:f5213. [PMID: 23963669]

Pagoto SL et al. A call for an end to the diet debates. JAMA. 2013 Aug 21;310(7):687–8. [PMID: 23989081]

Torpy JM et al. JAMA patient page. Bariatric surgery. JAMA. 2012 Sep 19;308(11):1173. [PMID: 22990277]

Tsai AG et al. In the clinic: obesity. Ann Intern Med. 2013 Sep 3;159(5):ITC3-1–15. [PMID: 24026335]

Unick JL et al; Look AHEAD Research Group. The long-term effectiveness of a lifestyle intervention in severely obese individuals. Am J Med. 2013 Mar;126(3):236–42. [PMID: 23410564]

Wang YC et al. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 2011 Aug 27;378(9793):815–25. [PMID: 21872750]

EATING DISORDERS

ANOREXIA NERVOSA

 ESSENTIALS OF DIAGNOSIS

 Disturbance of body image and intense fear of becoming fat.

 Weight loss leading to body weight 15% below expected.

 In females, absence of three consecutive menstrual cycles.

 General Considerations

Anorexia nervosa typically begins in the years between adolescence and young adulthood. Ninety percent of patients are females, most from the middle and upper socioeconomic strata.

The prevalence of anorexia nervosa is greater than previously suggested. In Rochester, Minnesota, for example, the prevalence per 100,000 population is estimated to be 270 for females and 22 for males. Many other adolescent girls have features of the disorder without the severe weight loss.

The cause of anorexia nervosa is not known. Although multiple endocrinologic abnormalities exist in these patients, most authorities believe they are secondary to malnutrition and not primary disorders. Most experts favor a primary psychiatric origin, but no hypothesis explains all cases. The patient characteristically comes from a family whose members are highly goal and achievement oriented. Interpersonal relationships may be inadequate or destructive. The parents are usually overly directive and concerned with slimness and physical fitness, and much of the family conversation centers around dietary matters. One theory holds that the patient’s refusal to eat is an attempt to regain control of her body in defiance of parental control. The patient’s unwillingness to inhabit an “adult body” may also represent a rejection of adult responsibilities and the implications of adult interpersonal relationships. Patients are commonly perfectionistic in behavior and exhibit obsessional personality characteristics. Marked depression or anxiety may be present.

 Clinical Findings

  1. Symptoms and Signs

Patients with anorexia nervosa may exhibit severe emaciation and may complain of cold intolerance or constipation. Amenorrhea is almost always present. Bradycardia, hypotension, and hypothermia may be present in severe cases. Examination demonstrates loss of body fat, dry and scaly skin, and increased lanugo body hair. Parotid enlargement and edema may also occur.

  1. Laboratory Findings

Laboratory findings are variable but may include anemia, leukopenia, electrolyte abnormalities, and elevations of blood urea nitrogen (BUN) and serum creatinine. Serum cholesterol levels are often increased. Endocrine abnormalities include depressed levels of luteinizing and follicle-stimulating hormones and impaired response of luteinizing hormone to luteinizing hormone-releasing hormone.

 Diagnosis & Differential Diagnosis

The diagnosis is based on the behavioral features of weight loss leading to body weight 15% below expected, a distorted body image, fear of weight gain or of loss of control over food intake and, in females, the absence of at least three consecutive menstrual cycles. Other medical or psychiatric illnesses that can account for anorexia and weight loss must be excluded.

Behavioral features required for the diagnosis include intense fear of becoming obese, disturbance of body image, weight loss of at least 15%, and refusal to exceed a minimal normal weight.

The differential diagnosis includes endocrine and metabolic disorders, such as panhypopituitarism, Addison disease, hyperthyroidism, and diabetes mellitus; gastrointestinal disorders, such as Crohn disease and celiac sprue; chronic infections and cancers, such as tuberculosis and lymphoma; and rare central nervous system disorders, such as hypothalamic tumors.

 Treatment

The goal of treatment is restoration of normal body weight and resolution of psychological difficulties. Hospitalization may be necessary. Treatment programs conducted by experienced teams are successful in about two-thirds of cases, restoring normal weight and menstruation. One-half continue to experience difficulties with eating behavior and psychiatric problems. Occasional patients with anorexia develop obesity after treatment. Two to 6% of patients die of the complications of the disorder or commit suicide.

Various treatment methods have been used without clear evidence of superiority of one over another. Supportive care by clinicians and family is probably the most important feature of therapy. Structured behavioral therapy, intensive psychotherapy, and family therapy may be tried. A variety of medications including tricyclic antidepressants, selected serotonin reuptake inhibitors (SSRIs), and lithium carbonate are effective in some cases; overall, however, clinical trial results have been disappointing. Patients with severe malnutrition must be hemodynamically stabilized and may require enteral or parenteral feeding. Forced feedings should be reserved for life-threatening situations, since the goal of treatment is to reestablish normal eating behavior.

 When to Refer

  • Adolescents and young adults with otherwise unexplained weight loss should be evaluated by a psychiatrist.
  • All patients with diagnosed anorexia nervosa should be co-managed with a psychiatrist.

 When to Admit

  • Signs of hypovolemia, major electrolyte disorders, and severe protein-energy malnutrition.
  • Failure to improve with outpatient management.

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Franko DL et al. A longitudinal investigation of mortality in anorexia nervosa and bulimia nervosa. Am J Psychiatry. 2013 Aug 1;170(8):917–25. [PMID: 23771148]

Ozier AD et al. Position of the American Dietetic Association: nutrition intervention in the treatment of eating disorders. J Am Diet Assoc. 2011 Aug;111(8):1236–41. [PMID: 21802573]

Sim LA et al. Identification and treatment of eating disorders in the primary care setting. Mayo Clin Proc. 2010 Aug;85(8):746–51. [PMID: 20605951]

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BULIMIA NERVOSA

 ESSENTIALS OF DIAGNOSIS

 Uncontrolled episodes of binge eating at least twice weekly for 3 months.

 Recurrent inappropriate compensation to prevent weight gain such as self-induced vomiting, laxatives, diuretics, fasting, or excessive exercise.

 Overconcern with weight and body shape.

 General Considerations

Bulimia nervosa is the episodic uncontrolled ingestion of large quantities of food followed by recurrent inappropriate compensatory behavior to prevent weight gain such as self-induced vomiting, diuretic or cathartic use, or strict dieting or vigorous exercise.

Like anorexia nervosa, bulimia nervosa is predominantly a disorder of young, white, middle- and upper-class women. It is more difficult to detect than anorexia, and some studies have estimated that the prevalence may be as high as 19% in college-aged women.

 Clinical Findings

Patients with bulimia nervosa typically consume large quantities of easily ingested high-calorie foods, usually in secrecy. Some patients may have several such episodes a day for a few days; others report regular and persistent patterns of binge eating. Binging is usually followed by vomiting, cathartics, or diuretics and is usually accompanied by feelings of guilt or depression. Periods of binging may be followed by intervals of self-imposed starvation. Body weights may fluctuate but generally are within 20% of desirable weights.

Some patients with bulimia nervosa also have a cryptic form of anorexia nervosa with significant weight loss and amenorrhea. Family and psychological issues are generally similar to those encountered among patients with anorexia nervosa. Bulimic patients, however, have a higher incidence of premorbid obesity, greater use of cathartics and diuretics, and more impulsive or antisocial behavior. Menstruation is usually preserved.

Medical complications are numerous. Gastric dilatation and pancreatitis have been reported after binges. Vomiting can result in poor dentition, pharyngitis, esophagitis, aspiration, and electrolyte abnormalities. Cathartic and diuretic abuse also cause electrolyte abnormalities or dehydration. Constipation and hemorrhoids are common.

 Treatment

Treatment of bulimia nervosa requires supportive care and psychotherapy. Individual, group, family, and behavioral therapy have all been utilized. Antidepressant medications may be helpful. The best results have been with fluoxetine hydrochloride and other SSRIs. Although death from bulimia is rare, the long-term psychiatric prognosis in severe bulimia is worse than that in anorexia nervosa.

 When to Refer

All patients with diagnosed bulimia should be co-managed with a psychiatrist.

Bulik CM et al. The changing “weightscape” of bulimia nervosa. Am J Psychiatry. 2012 Oct;169(10):1031–6. [PMID: 23032383]

Mehler PS. Medical complications of bulimia nervosa and their treatments. Int J Eat Disord. 2011 Mar;44(2):95–104. [PMID: 21312201]

Mitchell JE et al. Stepped care and cognitive-behavioural therapy for bulimia nervosa: randomized trial. Br J Psychiatry. 2011 May;198(5):391–7. [PMID: 21415046]

Ozier AD et al. Position of the American Dietetic Association: nutrition intervention in the treatment of eating disorders. J Am Diet Assoc. 2011 Aug;111(8):1236–41. [PMID: 21802573]

Umberg EN et al. From disordered eating to addiction: the “food drug” in bulimia nervosa. J Clin Psychopharmacol. 2012 Jun;32(3):376–89. [PMID: 22544008]

Wilson GT. Treatment of binge eating disorder. Psychiatr Clin North Am. 2011 Dec;34(4):773–83. [PMID: 22098803]

DISORDERS OF VITAMIN METABOLISM

THIAMINE (B1) DEFICIENCY

 ESSENTIALS OF DIAGNOSIS

 Most common in patients with chronic alcoholism.

 Early symptoms of anorexia, muscle cramps, paresthesias, irritability.

 Advanced syndromes of high output heart failure (“wet beriberi”), peripheral nerve disorders, and Wernicke-Korsakoff syndrome (“dry beriberi”).

 General Considerations

Most thiamine deficiency in the United States is due to alcoholism. Patients with chronic alcoholism may have poor dietary intakes of thiamine and impaired thiamine absorption, metabolism, and storage. Thiamine deficiency is also associated with malabsorption, dialysis, and other causes of chronic protein–calorie undernutrition. Thiamine deficiency can be precipitated in patients with marginal thiamine status with intravenous dextrose solutions.

 Clinical Findings

Early manifestations of thiamine deficiency include anorexia, muscle cramps, paresthesias, and irritability. Advanced deficiency primarily affects the cardiovascular system (“wet beriberi”) or the nervous system (“dry beriberi”). Wet beriberi occurs in thiamine deficiency accompanied by severe physical exertion and high carbohydrate intakes. Dry beriberi occurs in thiamine deficiency accompanied by inactivity and low calorie intake.

Wet beriberi is characterized by marked peripheral vasodilation resulting in high-output heart failure with dyspnea, tachycardia, cardiomegaly, and pulmonary and peripheral edema, with warm extremities mimicking cellulitis.

Dry beriberi involves both the peripheral and the central nervous systems. Peripheral nerve involvement is typically a symmetric motor and sensory neuropathy with pain, paresthesias, and loss of reflexes. The legs are affected more than the arms. Central nervous system involvement results in Wernicke–Korsakoff syndrome. Wernicke encephalopathy consists of nystagmus progressing to ophthalmoplegia, truncal ataxia, and confusion. Korsakoff syndrome includes amnesia, confabulation, and impaired learning.

 Diagnosis

In most instances, the clinical response to empiric thiamine therapy is used to support a diagnosis of thiamine deficiency. The most commonly used biochemical tests measure erythrocyte transketolase activity and urinary thiamine excretion. A transketolase activity coefficient > 15–20% suggests thiamine deficiency.

 Treatment

Thiamine deficiency is treated with large parenteral doses of thiamine. Fifty to 100 mg/d is administered intravenously for the first few days, followed by daily oral doses of 5–10 mg/d. All patients should simultaneously receive therapeutic doses of other water-soluble vitamins. Although treatment results in complete resolution in half of patients (one-fourth immediately and another one-fourth over days), the other half obtain only partial resolution or no benefit.

 When to Refer

Patients with signs of beriberi or Wernicke-Korsakoff syndrome should be referred to a neurologist.

THIAMINE TOXICITY

There is no known toxicity of thiamine.

Galvin R et al. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010 Dec;17(12):1408–18. [PMID: 20642790]

Kumar N. Neurologic presentations of nutritional deficiencies. Neurol Clin. 2010 Feb;28(1):107–70. [PMID: 19932379]

Lough ME. Wernicke’s encephalopathy: expanding the diagnostic toolbox. Neuropsychol Rev. 2012 Jun;22(2):181–94. [PMID: 22577001]

Sriram K et al. Thiamine in nutrition therapy. Nutr Clin Pract. 2012 Feb;27(1):41–50. [PMID: 22223666]

Yang JD et al. Beriberi disease: is it still present in the United States? Am J Med. 2012 Oct;125(10):e5. [PMID: 22800868]

Zahr NM et al. Clinical and pathological features of alcohol-related brain damage. Nat Rev Neurol. 2011 May;7(5):284–94. [PMID: 21487421]

RIBOFLAVIN (B2) DEFICIENCY

 Clinical Findings

Riboflavin deficiency almost always occurs in combination with deficiencies of other vitamins. Dietary inadequacy, interactions with a variety of medications, alcoholism, and other causes of protein–calorie undernutrition are the most common causes of riboflavin deficiency.

Manifestations of riboflavin deficiency include cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, weakness, corneal vascularization, and anemia.

 Diagnosis

Riboflavin deficiency can be confirmed by measuring the riboflavin-dependent enzyme erythrocyte glutathione reductase. Activity coefficients > 1.2–1.3 are suggestive of riboflavin deficiency. Urinary riboflavin excretion and serum levels of plasma and red cell flavins can also be measured.

 Treatment

Riboflavin deficiency is usually treated empirically when the diagnosis is suspected. It is easily treated with foods such as meat, fish, and dairy products or with oral preparations of the vitamin. Administration of 5–15 mg/d until clinical findings are resolved is usually adequate. Riboflavin can also be given parenterally, but it is poorly soluble in aqueous solutions.

RIBOFLAVIN TOXICITY

There is no known toxicity of riboflavin.

Koch TR et al. Postoperative metabolic and nutritional complications of bariatric surgery. Gastroenterol Clin North Am. 2010 Mar;39(1):109–24. [PMID: 20202584]

Powers HJ et al. Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM). Am J Clin Nutr. 2011 Jun;93(6):1274–84. [PMID: 21525198]

Tzoulaki I et al. A nutrient-wide association study on blood pressure. Circulation. 2012 Nov 20;126(21):2456–64. [PMID: 23093587]

NIACIN DEFICIENCY

 General Considerations

Niacin is a generic term for nicotinic acid and other derivatives with similar nutritional activity. Unlike most other vitamins, niacin can be synthesized from the amino acid tryptophan. Niacin is an essential component of the co-enzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in many oxidation-reduction reactions. The major food sources of niacin are protein foods containing tryptophan and numerous cereals, vegetables, and dairy products.

Niacin in the form of nicotinic acid is used therapeutically for the treatment of hypercholesterolemia and hypertriglyceridemia. Daily doses of 3–6 g can result in significant reductions in levels of LDL and very-low-density lipoproteins (VLDL) and in elevation of HDL. The AIM-HIGH study showed, however, that when added to statins there was no benefit of niacin on cardiovascular events.

Niacinamide (the form of niacin usually used to treat niacin deficiency) does not exhibit the lipid-lowering effects of nicotinic acid. Historically, niacin deficiency occurred when corn, which is relatively deficient in both tryptophan and niacin, was the major source of calories. Currently, niacin deficiency is more commonly due to alcoholism and nutrient–drug interactions. Niacin deficiency can also occur in inborn errors of metabolism.

 Clinical Findings

As with other B vitamins, the early manifestations of niacin deficiency are nonspecific. Common complaints include anorexia, weakness, irritability, mouth soreness, glossitis, stomatitis, and weight loss. More advanced deficiency results in the classic triad of pellagra: dermatitis, diarrhea, and dementia. The dermatitis is symmetric, involving sun-exposed areas. Skin lesions are dark, dry, and scaling. The dementia begins with insomnia, irritability, and apathy and progresses to confusion, memory loss, hallucinations, and psychosis. The diarrhea can be severe and may result in malabsorption due to atrophy of the intestinal villi. Advanced pellagra can result in death.

 Diagnosis

In early deficiency, diagnosis requires a high index of suspicion and attempts at confirmation of niacin deficiency. Niacin metabolites, particularly N-methylnicotinamide, can be measured in the urine. Low levels suggest niacin deficiency but may also be found in patients with generalized under-nutrition. Serum and red cell levels of NAD and NADP are also low but are similarly nonspecific. In advanced cases, the diagnosis of pellagra can be made on clinical grounds.

 Treatment

Niacin deficiency can be effectively treated with oral niacin, usually given as nicotinamide (10–150 mg/d).

NIACIN TOXICITY

At the high doses of niacin used to treat hyperlipidemia, side effects are common. These include cutaneous flushing (partially prevented by pretreatment with aspirin, 325 mg/d, and use of extended-release preparations) and gastric irritation. Elevation of liver enzymes, hyperglycemia, and gout are less common untoward effects.

Brown TM. Pellagra: an old enemy of timeless importance. Psychosomatics. 2010 Mar;51(2):93–7. [PMID: 20332283]

Jackevicius CA et al. Use of niacin in the United States and Canada. JAMA Intern Med. 2013 Jul 22;173(14):1379–81. [PMID: 23753308]

Michos ED et al. Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: reconciling the AIM-HIGH trial with previous surrogate endpoint trials. J Am Coll Cardiol. 2012 Jun 5;59(23):2058–64. [PMID: 22520249]

Wan P et al. Pellagra: a review with emphasis on photosensitivity. Br J Dermatol. 2011 Jun;164(6):1188–200. [PMID: 21128910]

VITAMIN B6 DEFICIENCY

Vitamin B6 deficiency most commonly occurs as a result of interactions with medications—especially isoniazid, cycloserine, penicillamine, and oral contraceptives—or of alcoholism. A number of inborn errors of metabolism and other pyridoxine-responsive syndromes, particularly pyridoxine-responsive anemia, are not clearly due to vitamin deficiency but commonly respond to high doses of the vitamin. Patients with common variable immunodeficiency may have concomitant vitamin B6 deficiency.

 Clinical Findings

Vitamin B6 deficiency results in a clinical syndrome similar to that seen with deficiencies of other B vitamins, including mouth soreness, glossitis, cheilosis, weakness, and irritability. Severe deficiency can result in peripheral neuropathy, anemia, and seizures. Studies have suggested a potential relationship of low vitamin B6 levels and a variety of clinical conditions including cardiovascular diseases, inflammatory diseases, and certain cancers.

 Diagnosis

The diagnosis of vitamin B6 deficiency can be confirmed by measurement of pyridoxal phosphate in blood. Normal levels are > 50 ng/mL.

 Treatment

Vitamin B6 deficiency can be effectively treated with oral vitamin B6 supplements (10–20 mg/d). Some patients taking medications that interfere with pyridoxine metabolism may need doses as high as 100 mg/d. Inborn errors of metabolism and the pyridoxine-responsive syndromes often require doses up to 600 mg/d.

Vitamin B6 should be routinely prescribed for patients receiving medications (such as isoniazid) that interfere with pyridoxine metabolism to prevent vitamin B6 deficiency. This is particularly true for patients who are more likely to have diets marginally adequate in vitamin B6, such as the elderly, alcoholic patients, or the urban poor. Clinical trials have shown that vitamin B6 supplementation, combined with other B vitamins, has no benefit on cardiovascular disease outcomes.

VITAMIN B6 TOXICITY

A sensory neuropathy, at times irreversible, occurs in patients receiving large doses of vitamin B6. Although most patients have taken 2 g or more per day, some patients have taken only 200 mg/d.

Corken M et al. Is vitamin B(6) deficiency an under-recognized risk in patients receiving haemodialysis? A systematic review: 2000–2010. Nephrology (Carlton). 2011 Sep;16(7):619–25. [PMID: 21609363]

Hisano M et al. Vitamin B6 deficiency and anemia in pregnancy. Eur J Clin Nutr. 2010 Feb;64(2):221–3. [PMID: 19920848]

Larsson SC et al. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA. 2010 Mar 17;303(11):1077–83. [PMID: 20233826]

Lotto V et al. Vitamin B6: a challenging link between nutrition and inflammation in CVD. Br J Nutr. 2011 Jul;106(2):183–95. [PMID: 21486513]

Mintzer S et al. B-vitamin deficiency in patients treated with antiepileptic drugs. Epilepsy Behav. 2012 Jul;24(3):341–4. [PMID: 22658435]

Zhang X et al. Prospective cohort studies of vitamin B-6 intake and colorectal cancer incidence: modification by time? Am J Clin Nutr. 2012 Oct;96(4):874–81. [PMID: 22875713]

VITAMIN B12 & FOLATE

Vitamin B12 (cobalamin) and folate are discussed in Chapter 13.

VITAMIN C (Ascorbic Acid) DEFICIENCY

Most cases of vitamin C deficiency seen in the United States are due to dietary inadequacy in the urban poor, the elderly, and patients with chronic alcoholism. Patients with chronic illnesses such as cancer and chronic kidney disease and individuals who smoke cigarettes are also at risk.

 Clinical Findings

Early manifestations of vitamin C deficiency are nonspecific and include malaise and weakness. In more advanced stages, the typical features of scurvy develop. Manifestations include perifollicular hemorrhages, perifollicular hyperkeratotic papules, petechiae and purpura, splinter hemorrhages, bleeding gums, hemarthroses, and subperiosteal hemorrhages. Periodontal signs do not occur in edentulous patients. Anemia is common, and wound healing is impaired. The late stages of scurvy are characterized by edema, oliguria, neuropathy, intracerebral hemorrhage, and death.

 Diagnosis

The diagnosis of advanced scurvy can be made clinically on the basis of the skin lesions in the proper clinical situation. Atraumatic hemarthrosis is also highly suggestive. The diagnosis can be confirmed with decreased plasma ascorbic acid levels, typically below 0.1 mg/dL.

 Treatment

Adult scurvy can be treated orally with 300–1000 mg of ascorbic acid per day. Improvement typically occurs within days. Clinical trials have shown that supplemental vitamin C has no benefit on cardiovascular disease or cancer outcomes.

VITAMIN C TOXICITY

Very large doses of vitamin C can cause gastric irritation, flatulence, or diarrhea. Oxalate kidney stones are of theoretic concern because ascorbic acid is metabolized to oxalate, but stone formation has not been frequently reported. Vitamin C can also confound common diagnostic tests by causing false-negative tests for fecal occult blood and both false-negative and false-positive tests for urine glucose.

Harrison FE. A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease. J Alzheimers Dis. 2012;29(4):711–26. [PMID: 22366772]

Hoffer LJ. Ascorbic acid supplements and kidney stone risk. JAMA Intern Med. 2013 Jul 22;173(14):1384. [PMID: 23877084]

Kupari M et al. Reversible pulmonary hypertension associated with vitamin C deficiency. Chest. 2012 Jul;142(1):225–7. [PMID: 22796843]

Magiorkinis E et al. Scurvy: past, present and future. Eur J Intern Med. 2011 Apr;22(2):147–52. [PMID: 21402244]

Pemberton J. Unrecognised scurvy. Signs and requirements. BMJ. 2010 Feb 2;340:c590. [PMID: 20124375]

VITAMIN A DEFICIENCY

 Clinical Findings

Vitamin A deficiency is one of the most common vitamin deficiency syndromes, particularly in developing countries. In many such regions, it is the most common cause of blindness. In the United States, vitamin A deficiency is usually due to fat malabsorption syndromes or mineral oil laxative abuse and occurs most commonly in the elderly and urban poor.

Night blindness is the earliest symptom. Dryness of the conjunctiva (xerosis) and the development of small white patches on the conjunctiva (Bitot spots) are early signs. Ulceration and necrosis of the cornea (keratomalacia), perforation, endophthalmitis, and blindness are late manifestations. Xerosis and hyperkeratinization of the skin and loss of taste may also occur.

 Diagnosis

Abnormalities of dark adaptation are strongly suggestive of vitamin A deficiency. Serum levels below the normal range of 30–65 mg/dL are commonly seen in advanced deficiency.

 Treatment

Night blindness, poor wound healing, and other signs of early deficiency can be effectively treated orally with 30,000 international units of vitamin A daily for 1 week. Advanced deficiency with corneal damage calls for administration of 20,000 international units/kg orally for at least 5 days. The potential antioxidant effects of beta-carotene can be achieved with supplements of 25,000–50,000 international units of beta-carotene.

VITAMIN A TOXICITY

Excess intake of beta-carotenes (hypercarotenosis) results in staining of the skin a yellow-orange color but is otherwise benign. Skin changes are most marked on the palms and soles, while the scleras remain white, clearly distinguishing hypercarotenosis from jaundice.

Excessive vitamin A (hypervitaminosis A), on the other hand, can be quite toxic. Chronic toxicity usually occurs after ingestion of daily doses of over 50,000 international units/d for > 3 months. Early manifestations include dry, scaly skin, hair loss, mouth sores, painful hyperostoses, anorexia, and vomiting. More serious findings include hypercalcemia; increased intracranial pressure, with papilledema, headaches, and decreased cognition; and hepatomegaly, occasionally progressing to cirrhosis. Excessive vitamin A has also recently been related to increased risk of hip fracture. Acute toxicity can result from ingestion of massive doses of vitamin A, such as in drug overdoses or consumption of polar bear liver. Manifestations include nausea, vomiting, abdominal pain, headache, papilledema, and lethargy.

The diagnosis can be confirmed by elevations of serum vitamin A levels. The only treatment is withdrawal of vitamin A from the diet. Most symptoms and signs improve rapidly.

Bello S et al. Routine vitamin A supplementation for the prevention of blindness due to measles infection in children. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD007719. [PMID: 21491401]

Checkley W et al. Maternal vitamin A supplementation and lung function in offspring. N Engl J Med. 2010 May 13;362(19): 1784–94. [PMID: 20463338]

Fok JS et al. Visual deterioration caused by vitamin A deficiency in patients after bariatric surgery. Eat Weight Disord. 2012 Jun;17(2):e144–6. [PMID: 23010786]

Sommer A et al. A global clinical view on vitamin A and carotenoids. Am J Clin Nutr. 2012 Nov;96(5):1204S–6S. [PMID: 23053551]

VITAMIN D

Vitamin D is discussed in Chapter 26.

VITAMIN E DEFICIENCY

 Clinical Findings

Clinical deficiency of vitamin E is most commonly due to severe malabsorption, the genetic disorder abetalipoproteinemia, or, in children with chronic cholestatic liver disease, biliary atresia or cystic fibrosis. Manifestations of deficiency include areflexia, disturbances of gait, decreased proprioception and vibration, and ophthalmoplegia.

 Diagnosis

Plasma vitamin E levels can be measured; normal levels are 0.5–0.7 mg/dL or higher. Since vitamin E is normally transported in lipoproteins, the serum level should be interpreted in relation to circulating lipids.

 Treatment

The optimum therapeutic dose of vitamin E has not been clearly defined. Large doses, often administered parenterally, can be used to improve the neurologic complications seen in abetalipoproteinemia and cholestatic liver disease. The potential antioxidant benefits of vitamin E can be achieved with supplements of 100–400 international units/d. Clinical trials of supplemental vitamin E to prevent cardiovascular disease, however, have shown no beneficial effects.

VITAMIN E TOXICITY

Clinical trials have suggested an increase in all-cause mortality with high dose (≥ 400 international units/d) vitamin E supplements. Large doses of vitamin E can also increase the vitamin K requirement and can result in bleeding in patients taking oral anticoagulants.

Bjelakovic G et al. Antioxidant supplements to prevent mortality. JAMA. 2013 Sep 18;310(11):1178–9. [PMID: 24045742]

Devore EE et al. Dietary antioxidants and long-term risk of dementia. Arch Neurol. 2010 Jul;67(7):819–25. [PMID: 20625087]

Dror DK et al. Vitamin E deficiency in developing countries. Food Nutr Bull. 2011 Jun;32(2):124–43. [PMID: 22164974]

Lotan Y et al. Evaluation of vitamin E and selenium supplementation for the prevention of bladder cancer in SWOG coordinated SELECT. J Urol. 2012 Jun;187(6):2005–10. [PMID: 22498220]

Suksomboon N et al. Effects of vitamin E supplementation on glycaemic control in type 2 diabetes: systematic review of randomized controlled trials. J Clin Pharm Ther. 2011 Feb;36(1):53–63. [PMID: 21198720]

VITAMIN K

Vitamin K is discussed in Chapter 14.

DIET THERAPY

In consultation with a registered dietician, specific therapeutic diets can be designed to facilitate the medical management of most common illnesses. Diet therapy is a difficult process, though, and not all patients are able to cooperate fully. Requesting the patient to record dietary intake for 3–5 days may provide useful insight into the patient’s motivation as well as providing nutrient information about the current diet.

Therapeutic diets can be divided into three groups: (1) diets that alter the consistency of food, (2) diets that restrict or otherwise modify dietary components, and (3) diets that supplement dietary components.

DIETS THAT ALTER CONSISTENCY

 Clear Liquid Diet

This diet provides adequate water, 500–1000 kcal as simple sugar, and some electrolytes. It is fiber free and requires minimal digestion or intestinal motility.

A clear liquid diet is useful for patients with resolving postoperative ileus, acute gastroenteritis, partial intestinal obstruction, and as preparation for diagnostic gastrointestinal procedures. It is commonly used as the first diet for patients who have been taking nothing by mouth for long periods. Because of the low calorie and minimal protein content of the clear liquid diet, it is used only for short periods.

 Full Liquid Diet

The full liquid diet provides adequate water and can be designed to provide adequate calories and protein. Vitamins and minerals—especially folic acid, iron, and vitamin B6—may be inadequate and should be provided in the form of supplements. Dairy products, soups, eggs, and soft cereals are used to supplement clear liquids. Commercial oral supplements can also be incorporated into the diet or used alone.

This diet is low in residue and can be used in many instances instead of the clear liquid diet described above—especially in patients with difficulty in chewing or swallowing, with partial obstructions, or in preparation for some diagnostic procedures. Full liquid diets are commonly used following clear liquid diets to advance diets in patients who have been taking nothing by mouth for long periods.

 Soft Diets

Soft diets are designed for patients unable to chew or swallow hard or coarse food. Tender foods are used, and most raw fruits and vegetables and coarse breads and cereals are eliminated. Soft diets are commonly used to assist in progression from full liquid diets to regular diets in postoperative patients, in patients who are too weak or those whose dentition is too poor to handle a general diet, in head andneck surgical patients, in patients with esophageal strictures, and in other patients who have difficulty with chewing or swallowing.

The soft diet can be designed to meet all nutritional requirements.

DIETS THAT RESTRICT NUTRIENTS

Diets can be designed to restrict (or eliminate) virtually any nutrient or food component. The most commonly used restricted diets are those that limit sodium, fat, and protein. Other restrictive diets include gluten restriction in sprue, potassium and phosphate reduction in chronic kidney disease, and various elimination diets for food allergies.

 Sodium-Restricted Diets

Low-sodium diets are useful in the management of hypertension and in conditions in which sodium retention and edema are prominent features, particularly heart failure, chronic liver disease, and chronic kidney disease. Sodium restriction is beneficial with or without diuretic therapy. When used in conjunction with diuretics, sodium restriction allows lower dosage of the diuretic medication and may prevent side effects. Potassium excretion, in particular, is directly related to distal renal tubule sodium delivery, and sodium restriction will decrease diuretic-related potassium losses.

Typical American diets contain 4–6 g (175–260 mEq) of sodium per day. A no-added-salt diet contains approximately 3 g (132 mEq) of sodium per day. Further restriction can be achieved with diets of 2 or 1 g of sodium per day. Diets with more severe restriction are poorly accepted by patients and are rarely used. Current Institute of Medicine guidelines recommend 2.3 g of sodium per day, which is approximately 1 teaspoon of salt.

Dietary sodium includes sodium naturally occurring in foods, sodium added during food processing, and sodium added by the consumer during cooking and at the table. About 80% of the current US dietary intake is from processed and pre-prepared foods. Diets designed for 2.3 g of sodium per day require elimination of most processed foods, added salt, and foods with particularly high sodium content. Patients who follow such diets for 2–3 months lose their craving for salty foods and can often continue to restrict their sodium intake indefinitely. Many patients with mild hypertension will achieve significant reductions in blood pressure (approximately 5 mm Hg diastolic) with this degree of sodium restriction.

Diets allowing 1 g of sodium require further restriction of commonly eaten foods. Special “low-sodium” products are available to facilitate such diets. These diets are difficult for most people to follow and are generally reserved for hospitalized patients and highly motivated outpatients—most commonly those with severe liver disease and ascites.

 Fat-Restricted Diets

Traditional fat-restricted diets are useful in the treatment of fat malabsorption syndromes. Such diets will improve the symptoms of diarrhea with steatorrhea independently of the primary physiologic abnormality by limiting the quantity of fatty acids that reach the colon. The degree of fat restriction necessary to control symptoms must be individualized. Patients with severe malabsorption can be limited to 40–60 g of fat per day. Diets containing 60–80 g of fat per day can be designed for patients with less severe abnormalities.

In general, fat-restricted diets require broiling, baking, or boiling meat and fish; discarding the skin of poultry and fish and using those foods as the main protein source; using nonfat dairy products; and avoiding desserts, sauces, and gravies.

 Low-Cholesterol, Low-Saturated-Fat Diets

Fat-restricted diets that specifically restrict saturated fats and dietary cholesterol are the mainstay of dietary treatment of hyperlipidemia (see Chapter 28). Similar diets are often recommended for diabetes mellitus (see Chapter 27) and for the prevention of coronary artery disease (see Chapter 10). The large Women’s Health Initiative Dietary Modification Trial, however, did not show any significant benefit of a low-fat diet on weight control or prevention of cardiovascular disease or cancer. In contrast, a study of Mediterranean diets, supplemented by nuts or extra-virgin olive oil, did demonstrate a reduction in cardiovascular events.

The aim of low-cholesterol, low-fat diets is to restrict total fat to < 30% of calories and to achieve a normal body weight by caloric restriction and increased physical activity. Saturated fat is restricted to 7% of calories and dietary cholesterol to 200 mg/d. Saturated fat can be replaced either with complex carbohydrates or, if energy balance permits, with monounsaturated fats. Saturated fat, total fat, and dietary cholesterol can be restricted further, but studies suggest that more extreme restriction offers little further advantage in overall modification of serum lipids. Cholesterol-lowering diets can be further augmented with the addition of plant stanols and sterols and with soluble dietary fiber.

 Protein-Restricted Diets

Protein-restricted diets are most commonly used in patients with hepatic encephalopathy due to chronic liver disease and in patients with advanced chronic kidney disease to slow the progression of early disease and to decrease symptoms of uremia in more severe disease. Patients with selected inborn errors of amino acid metabolism and other abnormalities resulting in hyperammonemia also require restriction of protein or of specific amino acids.

Protein restriction is intended to limit the production of nitrogenous waste products. Energy intake must be adequate to facilitate the efficient use of dietary protein. Proteins must be of high biologic value and be provided in sufficient quantity to meet minimal requirements. For most patients, the diet should contain at least 0.6 g/kg/d of protein. Patients with encephalopathy who do not respond to this degree of restriction are unlikely to respond to more severe restriction.

DIETS THAT SUPPLEMENT NUTRIENTS

 High-Fiber Diet

Dietary fiber is a diverse group of plant constituents that is resistant to digestion by the human digestive tract. Guidelines suggest that men eat 30–38 g/d and women 21–25 g/d. Typical US diets, however, contain about half of that amount. Epidemiologic evidence has suggested that populations consuming greater quantities of fiber have a lower incidence of certain gastrointestinal disorders, including diverticulitis and, in some studies, colon cancer and a lower risk of cardiovascular disease. A meta-analysis of 22 studies suggested that each 7 g of dietary fiber was associated with a 9% decrease in first cardiovascular events.

Diets high in dietary fiber (21–38 g/d) are also commonly used in the management of a variety of gastrointestinal disorders, particularly irritable bowel syndrome and recurrent diverticulitis. Diets high in fiber, particularly soluble fiber, may also be useful to reduce blood sugar in patients with diabetes and to reduce cholesterol levels in patients with hypercholesterolemia. Good sources of soluble fiber are oats, nuts, seeds, legumes and most fruits. Foods with insoluble fiber include whole wheat, brown rice, other whole grains, and most vegetables. For some patients, the addition of psyllium seed (2 tsp per day) or natural bran (one-half cup per day) may be a useful adjunct to increase dietary fiber.

High-Potassium Diets

Potassium-supplemented diets are used most commonly to compensate for potassium losses caused by diuretics. Although potassium losses can be partially prevented by using lower doses of diuretics, concurrent sodium restriction, and potassium-sparing diuretics, some patients require additional potassium to prevent hypokalemia. High-potassium diets may also have a direct antihypertensive effect. Typical American diets contain about 3 g (80 mEq) of potassium per day. High-potassium diets commonly contain 4.5–7 g (120–180 mEq) of potassium per day.

Most fruits, vegetables, and their juices contain high concentrations of potassium. Supplemental potassium can also be provided with potassium-containing salt substitutes (up to 20 mEq in one-quarter tsp) or as potassium chloride in solution or capsules, but this is rarely necessary if the above measures are followed to prevent potassium losses and supplement dietary potassium.

 High-Calcium Diets

Additional intakes of dietary calcium have been recommended for the prevention of postmenopausal osteoporosis, the prevention and treatment of hypertension, and the prevention of colon cancer. The Women’s Health Initiative, however, suggested that calcium and vitamin D supplementation did not prevent fractures or colon cancer. Observational studies have also suggested that calcium supplements, especially when taken without vitamin D, may be associated with an increased risk of coronary heart disease. The recommended dietary allowance for the total calcium intake (from food and supplements) in adults ranges from 1000 mg/d to 1200 mg/d. Average American daily intakes are approximately 700 mg/d.

Dairy products are the primary dietary sources of calcium in the United States. An 8-ounce glass of milk, for example, contains approximately 300 mg of calcium. Patients with lactose intolerance who cannot tolerate liquid dairy products may be able to use lactose-free milk, take supplemental lactase enzyme supplements, or tolerate nonliquid products such as cheese and yogurt. Leafy green vegetables and canned fish with bones also contain high concentrations of calcium, although the latter is also high in sodium.

Bao Y et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 2013 Nov 21;369(21):2001–11. [PMID: 24256379]

Baron RB. Eat more fibre. BMJ. 2013 Dec 19;347:f7401. [PMID: 24355540]

Baron RB. Should we all be vegetarians? JAMA Intern Med. 2013 Jul 8;173(13):1238–9. [PMID: 23836265]

Estruch R et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013 Apr 4;368(14):1279–90. Erratum in: N Engl J Med. 2014 Feb 27;370(9):886. [PMID: 23432189]

Hooper L et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD002137. [PMID: 21735388]

Jenkins DJ et al. Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial. JAMA. 2011 Aug 24;306(8):831–9. [PMID: 21862744]

Orlich MJ et al. Vegetarian dietary patterns and mortality in Adventist Health Study 2. JAMA Intern Med. 2013 Jul 8;173(13):1230–8. [PMID: 23836264]

Sacks FM et al. Dietary therapy in hypertension. N Engl J Med. 2010 Jun 3;362(22):2102–12. [PMID: 20519681]

Shikany JM et al. Effects of a low-fat dietary intervention on glucose, insulin, and insulin resistance in the Women’s Health Initiative (WHI) Dietary Modification trial. Am J Clin Nutr. 2011 Jul;94(1):75–85. [PMID: 21562091]

Threapleton DE et al. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2013 Dec 19;347:f6879. [PMID: 24355537]

INDICATIONS FOR NUTRITIONAL SUPPORT

The precise indications for nutritional support remain controversial. Most authorities agree that nutritional support is indicated for at least four groups of adult patients: (1) those with inadequate bowel syndromes, (2) those with severe prolonged hypercatabolic states (eg, due to extensive burns, multiple trauma, mechanical ventilation), (3) those requiring prolonged therapeutic bowel rest, and (4) those with severe protein–calorie undernutrition with a treatable disease who have sustained a loss of over 25% of body weight.

It has been difficult to prove the efficacy of nutritional support in the treatment of most other conditions. In most cases it has not been possible to show a clear advantage of treatment by means of nutritional support over treatment without such support.

The American Society for Parenteral and Enteral Nutrition (ASPEN) has published recommendations for the rational use of nutritional support. The recommendations emphasize the need to individualize the decision to begin nutritional support, weighing the risks and costs against the benefits to each patient. They also reinforce the need to identify high-risk malnourished patients by nutritional assessment.

 NUTRITIONAL SUPPORT METHODS

Selection of the most appropriate nutritional support method involves consideration of gastrointestinal function, the anticipated duration of nutritional support, and the ability of each method to meet the patient’s nutritional requirements. The method chosen should meet the patient’s nutritional needs with the lowest risk and lowest cost possible. For most patients, enteral feeding is safer and cheaper and offers significant physiologic advantages. An algorithm for selection of the most appropriate nutritional support method is presented in Figure 29–1.

 Figure 29–1. Nutritional support method decision tree.

Prior to initiating specialized enteral nutritional support, efforts should be made to supplement food intake. Attention to patient preferences, timing of meals and diagnostic procedures and use of medications, and the use of foods brought to the hospital by family and friends can often increase oral intake. Patients unable to eat enough at regular mealtimes to meet nutritional requirements can be given oral supplements as snacks or to replace low-calorie beverages. Oral supplements of differing nutritional composition are available for the purpose of individualizing the diet in accordance with specific clinical requirements. Fiber and lactose content, caloric density, protein level, amino acid profiles, vitamin K, and calcium can all be modified as necessary.

Patients unable to take adequate oral nutrients who have functioning gastrointestinal tracts and who meet the criteria for nutritional support are candidates for tube feedings. Small-bore feeding tubes are placed via the nose into the stomach or duodenum. Patients able to sit up in bed who can protect their airways can be fed into the stomach. Because of the increased risk of aspiration, patients who cannot adequately protect their airways should be fed nasoduodenally. Feeding tubes can usually be passed into the duodenum by leaving an extra length of tubing in the stomach and placing the patient in the right decubitus position. Metoclopramide, 10 mg intravenously, can be given 20 minutes prior to insertion and continued every 6 hours thereafter to facilitate passage through the pylorus. Occasionally, patients will require fluoroscopic or endoscopic guidance to insert the tube distal to the pylorus. Placement of nasogastric and, particularly, nasoduodenal tubes should be confirmed radiographically before delivery of feeding solutions.

Feeding tubes can also be placed directly into the gastrointestinal tract using tube enterostomies. Most tube enterostomies are placed in patients who require long-term enteral nutritional support. Gastrostomies have the advantage of allowing bolus feedings, while jejunostomies require continuous infusions. Gastrostomies—like nasogastric feeding—should be used only in patients at low risk for aspiration. Gastrostomies can also be placed percutaneously with the aid of endoscopy. These tubes can then be advanced to jejunostomies. Tube enterostomies can also be placed surgically.

Patients who require nutritional support but whose gastrointestinal tracts are nonfunctional should receive parenteral nutritional support. Most patients receive parenteral feedings via a central vein—most commonly the subclavian vein. Peripheral veins can be used in some patients, but because of the high osmolality of parenteral solutions this is rarely tolerated for more than a few weeks.

Peripheral vein nutritional support is most commonly used in patients with nonfunctioning gastrointestinal tracts who require immediate support but whose clinical status is expected to improve within 1–2 weeks, allowing enteral feeding. Peripheral vein nutritional support is administered via standard intravenous lines. Solutions should always include lipid and dextrose in combination with amino acids to provide adequate nonprotein calories. Serious side effects are infrequent, but there is a high incidence of phlebitis and infiltration of intravenous lines.

Central vein nutritional support is delivered via intravenous catheters placed percutaneously using aseptic technique. Proper placement in the superior vena cava is documented radiographically before the solution is infused. Catheters must be carefully maintained by experienced nursing personnel and used solely for nutritional support to prevent infection and other catheter-related complications.

NUTRITIONAL REQUIREMENTS

Each patient’s nutritional requirements should be determined independently of the method of nutritional support. In most situations, solutions of equal nutrient value can be designed for delivery via enteral and parenteral routes, but differences in absorption must be considered. A complete nutritional support solution must contain water, energy, amino acids, electrolytes, vitamins, minerals, and essential fatty acids.

 Water

For most patients, water requirements can be calculated by allowing 1500 mL for the first 20 kg of body weight plus 20 mL for every kilogram over 20. Additional losses should be replaced as they occur. For average-sized adult patients, fluid needs are about 30–35 mL/kg, or approximately 1 mL/kcal of energy required (see below).

 Energy

Energy requirements can be estimated by one of three methods: (1) by using standard equations to calculate BEE plus additional calories for activity and illness, (2) by applying a simple calculation based on calories per kilogram of body weight, or (3) by measuring energy expenditure with indirect calorimetry.

BEE can be estimated by the Harris–Benedict equation: for men, BEE = 666 + (13.7 × weight in kg) + (5 × height in cm) – (6.8 × age in years). For women, BEE = 655 + (9.5 × weight in kg) + (1.8 × height in cm) – (4.7 × age in years). For undernourished patients, actual body weight should be used; for obese patients, ideal body weight should be used. For most patients, an additional 20–50% of BEE is administered as nonprotein calories to accommodate energy expenditures during activity or relating to the illness. Occasional patients are noted to have energy expenditures > 150% of BEE.

Energy requirements can be estimated also by multiplying actual body weight in kilograms (for obese patients, ideal body weight) by 30–35 kcal.

Both of these methods provide imprecise estimates of actual energy expenditures, especially for the markedly underweight, overweight, and critically ill patient. Studies using indirect calorimetry have demonstrated that as many as 30–40% of patients will have measured expenditures 10% above or below estimated values. For accurate determination of energy expenditure, indirect calorimetry should be used.

 Protein

Protein and energy requirements are closely related. If adequate calories are provided, most patients can be given 0.8–1.2 g of protein per kilogram per day. Patients undergoing moderate to severe stress should receive up to 1.5 g/kg/d. As in the case of energy requirements, actual weights should be used for normal and underweight patients and ideal weights for patients with significant obesity.

Patients who are receiving protein without adequate calories will catabolize protein for energy rather than utilizing it for protein synthesis. Thus, when energy intake is low, excess protein is needed for nitrogen balance. If both energy and protein intakes are low, extra energy will have a more significant positive effect on nitrogen balance than extra protein.

 Electrolytes & Minerals

Requirements for sodium, potassium, and chloride vary widely. Most patients require 45–145 mEq/d of each. The actual requirement in individual patients will depend on the patient’s cardiovascular, renal, endocrine, and gastrointestinal status as well as measurements of serum concentration.

Patients receiving enteral nutritional support should receive adequate vitamins and minerals according to the recommended daily allowances. Most premixed enteral solutions provide adequate vitamins and minerals as long as adequate calories are administered.

Patients receiving parenteral nutritional support require smaller amounts of minerals: calcium, 10–15 mEq/d; phosphorus, 15–20 mEq per 1000 nonprotein calories; and magnesium, 16–24 mEq/d. Most patients receiving nutritional support do not require supplemental iron because body stores are adequate. Iron nutrition should be monitored closely by following the hemoglobin concentration, mean corpuscular volume, and iron studies. Parenteral administration of iron is associated with a number of adverse effects and should be reserved for iron-deficient patients unable to take oral iron.

Patients receiving parenteral nutritional support should be given the trace elements zinc (about 5 mg/d) and copper (about 2 mg/d). Patients with diarrhea will require additional zinc to replace fecal losses. Additional trace elements—especially chromium, manganese, and selenium—are provided to patients receiving long-term parenteral nutrition.

Parenteral vitamins are provided daily. Standardized multivitamin solutions are currently available to provide adequate quantities of vitamins A, B12, C, D, E, thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid, and biotin. Vitamin K is not given routinely but administered when the prothrombin time becomes abnormal.

 Essential Fatty Acids

Patients receiving nutritional support should be given 2–4% of their total calories as linoleic acid to prevent essential fatty acid deficiency. Most prepared enteral solutions contain adequate linoleic acid. Patients receiving parenteral nutrition should be given at least 250 mL of a 20% intravenous fat (emulsified soybean or safflower oil) about two or three times a week. Intravenous fat can also be used as an energy source in place of dextrose.

ENTERAL NUTRITIONAL SUPPORT SOLUTIONS

Most patients who require enteral nutritional support can be given commercially prepared enteral solutions (Table 29–1). Nutritionally complete solutions have been designed to provide adequate proportions of water, energy, protein, and micronutrients. Nutritionally incomplete solutions are also available to provide specific macronutrients (eg, protein, carbohydrate, and fat) to supplement complete solutions for patients with unusual requirements or to design solutions that are not available commercially.

Table 29–1. Enteral solutions.

Nutritionally complete solutions are characterized as follows: (1) by osmolality (isotonic or hypertonic), (2) by lactose content (present or absent), (3) by the molecular form of the protein component (intact proteins; peptides or amino acids), (4) by the quantity of protein and calories provided, and (5) by fiber content (present or absent). For most patients, isotonic solutions containing no lactose or fiber are preferable. Such solutions generally contain moderate amounts of fat and intact protein. Most commercial isotonic solutions contain 1000 kcal and about 37–45 g of protein per liter.

Solutions containing hydrolyzed proteins or crystalline amino acids and with no significant fat content are called elemental solutions, since macronutrients are provided in their most “elemental” form. These solutions have been designed for patients with malabsorption, particularly pancreatic insufficiency and limited fat absorption. Elemental diets are extremely hypertonic and often result in more severe diarrhea. Their use should be limited to patients who cannot tolerate isotonic solutions.

Although formulas have been designed for specific clinical situations—solutions containing primarily essential amino acids (for advanced chronic kidney disease), medium-chain triglycerides (for fat malabsorption), more fat (for respiratory failure and CO2 retention), and more branched-chain amino acids (for hepatic encephalopathy and severe trauma)—they have not been shown to be superior to standard formulas for most patients.

Enteral solutions should be administered via continuous infusion, preferably with an infusion pump. Isotonic feedings should be started at full strength at about 25–33% of the estimated final infusion rate. Feedings can be advanced by similar amounts every 12 hours as tolerated. Hypertonic feedings should be started at half strength. The strength and the rate can then be advanced every 6 hours as tolerated.

COMPLICATIONS OF ENTERALNUTRITIONAL SUPPORT

Minor complications of tube feedings occur in 10–15% of patients. Gastrointestinal complications include diarrhea (most common), inadequate gastric emptying, emesis, esophagitis, and occasionally gastrointestinal bleeding. Diarrhea associated with tube feeding may be due to intolerance to the osmotic load or to one of the macronutrients (eg, fat, lactose) in the solution. Patients being fed in this way may also have diarrhea from other causes (as side effects of antibiotics or other drugs, associated with infection, etc), and these possibilities should always be investigated in appropriate circumstances.

Mechanical complications of tube feedings are potentially the most serious. Of particular importance is aspiration. All patients receiving nasogastric tube feedings are at risk for this life-threatening complication. Limiting nasogastric feedings to those patients who can adequately protect their airway and careful monitoring of patients being fed by tube should limit these serious complications to 1–2% of cases. Minor mechanical complications are common and include tube obstruction and dislodgment.

Metabolic complications during enteral nutritional support are common but in most cases are easily managed. The most important problem is hypernatremic dehydration, most commonly seen in elderly patients given excessive protein intake who are unable to respond to thirst. Abnormalities of potassium, glucose, CO2 production, and acid–base balance may also occur.

PARENTERAL NUTRITIONALSUPPORT SOLUTIONS

Parenteral nutritional support solutions can be designed to deliver adequate nutrients to most patients. The basic parenteral solution is composed of dextrose, amino acids, and water. Electrolytes, minerals, trace elements, vitamins, and medications can also be added. Most commercial solutions contain the monohydrate form of dextrose that provides 3.4 kcal/g. Crystalline amino acids are available in a variety of concentrations, so that a broad range of solutions can be made up that will contain specific amounts of dextrose and amino acids as required.

Typical solutions for central vein nutritional support contain 25–35% dextrose and 2.75–6% amino acids depending upon the patient’s estimated nutrient and water requirements. These solutions typically have osmolalities in excess of 1800 mosm/L and require infusion into a central vein. A typical formula for patients without organ failure is shown in Table 29–2.

Table 29–2. Typical parenteral nutrition solution (for stable patients without organ failure).

Solutions with lower osmolalities can also be designed for infusion into peripheral veins. Typical solutions for peripheral infusion contain 5–10% dextrose and 2.75–4.25% amino acids. These solutions have osmolalities between 800 and 1200 mosm/L and result in a high incidence of thrombophlebitis and line infiltration. These solutions will provide adequate protein for most patients but inadequate energy. Additional energy must be provided in the form of emulsified soybean or safflower oil. Such intravenous fat solutions are currently available in 10% and 25% solutions providing 1.1 and 2.2 kcal/mL, respectively. Intravenous fat solutions are isosmotic and well tolerated by peripheral veins.

Typical patients are given 200–500 mL of a 20% solution each day. As much as 60% of total calories can be administered in this manner.

Intravenous fat can also be provided to patients receiving central vein nutritional support. In this instance, dextrose concentrations should be decreased to provide a fixed concentration of energy. Intravenous fat has been shown to be equivalent to intravenous dextrose in providing energy to spare protein. Intravenous fat is associated with less glucose intolerance, less production of carbon dioxide, and less fatty infiltration of the liver and has been increasingly utilized in patients with hyperglycemia, respiratory failure, and liver disease. Intravenous fat has also been increasingly used in patients with large estimated energy requirements. The maximum glucose utilization rate is approximately 5–7 mg/min/kg. Patients who require additional calories can be given them as fat to prevent excess administration of dextrose. Intravenous fat can also be used to prevent essential fatty acid deficiency. The optimal ratio of carbohydrate and fat in parenteral nutritional support has not been determined.

Infusion of parenteral solutions should be started slowly to prevent hyperglycemia and other metabolic complications. Typical solutions are given initially at a rate of 50 mL/h and advanced by about the same amount every 24 hours until the desired final rate is reached.

COMPLICATIONS OF PARENTERAL NUTRITIONAL SUPPORT

Complications of central vein nutritional support occur in up to 50% of patients. Although most are minor and easily managed, significant complications will develop in about 5% of patients. Complications of central vein nutritional support can be divided into catheter-related complications and metabolic complications.

Catheter-related complications can occur during insertion or while the catheter is in place. Pneumothorax, hemothorax, arterial laceration, air emboli, and brachial plexus injury can occur during catheter placement. The incidence of these complications is inversely related to the experience of the physician performing the procedure but will occur in at least 1–2% of cases even in major medical centers. Each catheter placement should be documented by chest radiograph prior to initiation of nutritional support.

Catheter thrombosis and catheter-related sepsis are the most important complications of indwelling catheters. Patients with indwelling central vein catheters in whom fever develops without an apparent source should have their lines changed over a wire or removed immediately, the tip quantitatively cultured, and antibiotics begun empirically. Quantitative tip cultures and blood cultures will help guide further antibiotic therapy. Catheter-related sepsis occurs in 2–3% of patients even if maximal efforts are made to prevent infection.

Metabolic complications of central vein nutritional support occur in over 50% of patients (Table 29–3). Most are minor and easily managed, and termination of support is seldom necessary.

Table 29–3. Metabolic complications of parenteral nutritional support.

PATIENT MONITORING DURING NUTRITIONAL SUPPORT

Every patient receiving enteral or parenteral nutritional support should be monitored closely. Formal nutritional support teams composed of a physician, a nurse, a dietitian, and a pharmacist have been shown to decrease the rate of complications.

Patients should be monitored both for the adequacy of treatment and to prevent complications or detect them early when they occur. Because estimates of nutritional requirements are imprecise, frequent reassessment is necessary. Daily intakes should be recorded and compared with estimated requirements. Body weight, hydration status, and overall clinical status should be followed. Patients who do not appear to be responding as anticipated can be evaluated for nitrogen balance by means of the following equation:

Patients with positive nitrogen balances can be continued on their current regimens; patients with negative balances should receive moderate increases in calorie and protein intake and then be reassessed. Monitoring for metabolic complications includes daily measurements of electrolytes; serum glucose, phosphorus, magnesium, calcium, and creatinine; and BUN until the patient is stabilized. Once the patient is stabilized, electrolytes, phosphorus, calcium, magnesium, and glucose should be obtained at least twice weekly. Red blood cell folate, zinc, and copper should be checked at least once a month.

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