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InternalMed_Harrison. months. Manifestations include dry skin, cheilosis, glossitis, vomiting, alopecia, bone demineralization and pain, hypercalcemia, lymph node enlargement, hyperlipidemia, amenorrhea, and features of pseudotumor cerebri with increased intracranial pressure and papilledema. Liver fibrosis with portal hypertension and 96e-7 bone demineralization may result from chronic vitamin A intoxication. Provision of vitamin A in excess to pregnant women has resulted in spontaneous abortion and in congenital malformations, including craniofacial abnormalities and valvular heart disease. In pregnancy, the daily dose of vitamin A should not exceed 3 mg. Commercially available retinoid derivatives are also toxic, including 13-cis-retinoic acid, which has been associated with birth defects. Thus contraception should be continued for at least 1 year and possibly longer in women who have taken 13-cis-retinoic acid.


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InternalMed_Harrison. In malnourished children, vitamin A supplements (30–60 mg), in amounts calculated as a function of age and given in several rounds over 2 years, are considered to amplify nonspecific effects of vaccines. However, for unclear reasons, there may be a negative effect on mortality rates in incompletely vaccinated girls.


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InternalMed_Harrison. High doses of carotenoids do not result in toxic symptoms but should be avoided in smokers due to an increased risk of lung cancer. Very high doses of β-carotene (~200 mg/d) have been used to treat or prevent the skin rashes of erythropoietic protoporphyria. Carotenemia, which is characterized by a yellowing of the skin (in creases of the palms and soles) but not the sclerae, may follow ingestion of >30 mg of β-carotene daily. Hypothyroid patients are particularly susceptible to the development of carotenemia due to impaired breakdown of carotene to vitamin A. Reduction of carotenes in the diet results in the disappearance of skin yellowing and carotenemia over a period of 30–60 days.


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InternalMed_Harrison. The metabolism of the fat-soluble vitamin D is described in detail in Chap. 423. The biologic effects of this vitamin are mediated by vitamin D receptors, which are found in most tissues; binding with these receptors potentially expands vitamin D actions on nearly all cell systems and organs (e.g., immune cells, brain, breast, colon, and prostate) as well as exerting classic endocrine effects on calcium metabolism and bone health. Vitamin D is thought to be important for maintaining normal function of many nonskeletal tissues such as muscle (including heart muscle), for immune function, and for inflammation as well as for cell proliferation and differentiation. Studies have shown that vitamin D may be useful as adjunctive treatment for tuberculosis, psoriasis, and multiple sclerosis or for the prevention of certain cancers. Vitamin D insufficiency may increase the risk of type 1 diabetes mellitus, cardiovascular disease (insulin resistance, hypertension, or low-grade inflammation), or


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InternalMed_Harrison. the prevention of certain cancers. Vitamin D insufficiency may increase the risk of type 1 diabetes mellitus, cardiovascular disease (insulin resistance, hypertension, or low-grade inflammation), or brain dysfunction (e.g., depression). However, the exact physiologic roles of vitamin D in these nonskeletal diseases and the importance of these roles have not been clarified.


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InternalMed_Harrison. The skin is a major source of vitamin D, which is synthesized upon skin exposure to ultraviolet B radiation (UV-B; wavelength, 290–320 nm). Except for fish, food (unless fortified) contains only limited amounts of vitamin D. Vitamin D2 (ergocalciferol) is obtained from plant sources and is the chemical form found in some supplements.


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InternalMed_Harrison. Deficiency Vitamin D status has been assessed by measuring serum levels of 25-dihydroxyvitamin D (25[OH]2 vitamin D); however, there is no consensus on a uniform assay or on optimal serum levels. The optimal level might, in fact, differ according to the targeted disease entity. Epidemiologic and experimental data indicate that a 25(OH)2 vitamin D level of >20 ng/mL (≥50 nmol/L; to convert ng/mL to nmol/L, multiply by 2.496) is sufficient for good bone health. Some experts advocate higher serum levels (e.g., >30 ng/mL) for other desirable endpoints of vitamin D action. There is insufficient evidence to recommend combined vitamin D and calcium supplementation as a primary preventive strategy for reduction of the incidence of fractures in healthy men and premenopausal women.


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InternalMed_Harrison. Risk factors for vitamin D deficiency are old age, lack of sun exposure, dark skin (especially among residents of northern latitudes), fat malabsorption, and obesity. Rickets represents the classic disease of vitamin D deficiency. Signs of deficiency are muscle soreness, weakness, and bone pain. Some of these effects are independent of calcium intake.


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InternalMed_Harrison. 96e-8 The U.S. National Academy of Sciences recently concluded that the majority of North Americans are receiving adequate amounts of vitamin D (RDA = 15 μg/d or 600 IU/d; Chap. 95e). However, for people older than 70 years, the RDA is set at 20 μg/d (800 IU/d). The consumption of fortified or enriched foods as well as suberythemal sun exposure should be encouraged for people at risk for vitamin D deficiency. If adequate intake is impossible, vitamin D supplements should be taken, especially during the winter months. Vitamin D deficiency can be treated by the oral administration of 50,000 IU/week for 6–8 weeks followed by a maintenance dose of 800 IU/d (100 μg/d) from food and supplements once normal plasma levels have been attained. The physiologic effects of vitamin D2 and vitamin D3 are identical when these vitamins are ingested over long periods.


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InternalMed_Harrison. Toxicity The upper limit of intake has been set at 4000 IU/d. Contrary to earlier beliefs, acute vitamin D intoxication is rare and usually is caused by the uncontrolled and excessive ingestion of supplements or by faulty food fortification practices. High plasma levels of 1,25(OH)2 vitamin D and calcium are central features of toxicity and mandate discontinuation of vitamin D and calcium supplements; in addition, treatment of hypercalcemia may be required.


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InternalMed_Harrison. Vitamin E is the collective designation for all stereoisomers of tocopherols and tocotrienols, although only the RR tocopherols meet human requirements. Vitamin E acts as a chain-breaking antioxidant and is an efficient pyroxyl radical scavenger that protects low-density lipoproteins and polyunsaturated fats in membranes from oxidation. A network of other antioxidants (e.g., vitamin C, glutathione) and enzymes maintains vitamin E in a reduced state. Vitamin E also inhibits prostaglandin synthesis and the activities of protein kinase C and phospholipase A2. Absorption and Metabolism After absorption, vitamin E is taken up from chylomicrons by the liver, and a hepatic α-tocopherol transport protein mediates intracellular vitamin E transport and incorporation into very low density lipoprotein. The transport protein has a particular affinity for the RRR isomeric form of α-tocopherol; thus, this natural isomer has the most biologic activity.


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InternalMed_Harrison. requirement Vitamin E is widely distributed in the food supply, with particularly high levels in sunflower oil, safflower oil, and wheat germ oil; γ-tocotrienols are notably present in soybean and corn oils. Vitamin E is also found in meats, nuts, and cereal grains, and small amounts are present in fruits and vegetables. Vitamin E pills containing doses of 50–1000 mg are ingested by ~10% of the U.S. population. The RDA for vitamin E is 15 mg/d (34.9 μmol or 22.5 IU) for all adults. Diets high in polyunsaturated fats may necessitate a slightly higher intake of vitamin E.


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InternalMed_Harrison. Dietary deficiency of vitamin E does not exist. Vitamin E deficiency is seen only in severe and prolonged malabsorptive diseases, such as celiac disease, or after small-intestinal resection or bariatric surgery. Children with cystic fibrosis or prolonged cholestasis may develop vitamin E deficiency characterized by areflexia and hemolytic anemia. Children with abetalipoproteinemia cannot absorb or transport vitamin E and become deficient quite rapidly. A familial form of isolated vitamin E deficiency also exists; it is due to a defect in the α-tocopherol transport protein. Vitamin E deficiency causes axonal degeneration of the large myelinated axons and results in posterior column and spinocerebellar symptoms. Peripheral neuropathy is initially characterized by areflexia, with progression to an ataxic gait, and by decreased vibration and position sensations. Ophthalmoplegia, skeletal myopathy, and pigmented retinopathy may also be features of vitamin E deficiency. A deficiency of


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InternalMed_Harrison. to an ataxic gait, and by decreased vibration and position sensations. Ophthalmoplegia, skeletal myopathy, and pigmented retinopathy may also be features of vitamin E deficiency. A deficiency of either vitamin E or selenium in the host has been shown to increase certain viral mutations and, therefore, virulence. The laboratory diagnosis of vitamin E deficiency is based on low blood levels of α-tocopherol (<5 μg/mL, or <0.8 mg of α-tocopherol per gram of total lipids).


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InternalMed_Harrison. Symptomatic vitamin E deficiency should be treated with 800–1200 mg of α-tocopherol per day. Patients with abetalipoproteinemia may need as much as 5000–7000 mg/d. Children with symptomatic vitamin E deficiency should be treated orally with water-miscible esters (400 mg/d); alternatively, 2 mg/kg per day may be administered intramuscularly. Vitamin E in high doses may protect against oxygen-induced retrolental fibroplasia and bronchopulmonary dysplasia as well as intraventricular hemorrhage of prematurity. Vitamin E has been suggested to increase sexual performance, treat intermittent claudication, and slow the aging process, but evidence for these properties is lacking. When given in combination with other antioxidants, vitamin E may help prevent macular degeneration. High doses (60–800 mg/d) of vitamin E have been shown in controlled trials to improve parameters of immune function and reduce colds in nursing home residents, but intervention studies using vitamin E to prevent


InternalMed_Harrison

InternalMed_Harrison. mg/d) of vitamin E have been shown in controlled trials to improve parameters of immune function and reduce colds in nursing home residents, but intervention studies using vitamin E to prevent cardiovascular disease or cancer have not shown efficacy, and, at doses >400 mg/d, vitamin E may even increase all-cause mortality rates.


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InternalMed_Harrison. Toxicity All forms of vitamin E are absorbed and could contribute to toxicity; however, the toxicity risk seems to be rather low as long as liver function is normal. High doses of vitamin E (>800 mg/d) may reduce platelet aggregation and interfere with vitamin K metabolism and are therefore contraindicated in patients taking warfarin and anti-platelet agents (such as aspirin or clopidogrel). Nausea, flatulence, and diarrhea have been reported at doses >1 g/d. There are two natural forms of vitamin K: vitamin K1, also known as phylloquinone, from vegetable and animal sources, and vitamin K2, or menaquinone, which is synthesized by bacterial flora and found in hepatic tissue. Phylloquinone can be converted to menaquinone in some organs.


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InternalMed_Harrison. Vitamin K is required for the posttranslational carboxylation of glutamic acid, which is necessary for calcium binding to γ-carboxylated proteins such as prothrombin (factor II); factors VII, IX, and X; protein C; protein S; and proteins found in bone (osteocalcin) and vascular smooth muscle (e.g., matrix Gla protein). However, the importance of vitamin K for bone mineralization and prevention of vascular calcification is not known. Warfarin-type drugs inhibit γ-carboxylation by preventing the conversion of vitamin K to its active hydroquinone form. Dietary Sources Vitamin K is found in green leafy vegetables such as kale and spinach, and appreciable amounts are also present in margarine and liver. Vitamin K is present in vegetable oils; olive, canola, and soybean oils are particularly rich sources. The average daily intake by Americans is estimated to be ~100 μg/d.


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InternalMed_Harrison. Deficiency The symptoms of vitamin K deficiency are due to hemorrhage; newborns are particularly susceptible because of low fat stores, low breast milk levels of vitamin K, relative sterility of the infantile intestinal tract, liver immaturity, and poor placental transport. Intracranial bleeding as well as gastrointestinal and skin bleeding can occur in vitamin K–deficient infants 1–7 days after birth. Thus, vitamin K (0.5–1 mg IM) is given prophylactically at delivery.


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InternalMed_Harrison. Vitamin K deficiency in adults may be seen in patients with chronic small-intestinal disease (e.g., celiac disease, Crohn’s disease), in those with obstructed biliary tracts, or after small-bowel resection. Broad-spectrum antibiotic treatment can precipitate vitamin K deficiency by reducing numbers of gut bacteria, which synthesize menaquinones, and by inhibiting the metabolism of vitamin K. In patients with warfarin therapy, the anti-obesity drug orlistat can lead to international normalized ratio changes due to vitamin K malabsorption. Vitamin K deficiency usually is diagnosed on the basis of an elevated prothrombin time or reduced clotting factors, although vitamin K may also be measured directly by high-pressure liquid chromatography. Vitamin K deficiency is treated with a parenteral dose of 10 mg. For patients with chronic malabsorption, 1–2 mg/d should be given orally or 1–2 mg per week can be taken parenterally. Patients with liver disease may have an elevated prothrombin time


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InternalMed_Harrison. dose of 10 mg. For patients with chronic malabsorption, 1–2 mg/d should be given orally or 1–2 mg per week can be taken parenterally. Patients with liver disease may have an elevated prothrombin time because of liver cell destruction as well as vitamin K deficiency. If an elevated prothrombin time does not improve during vitamin K therapy, it can be deduced that this abnormality is not the result of vitamin K deficiency.


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InternalMed_Harrison. Toxicity Toxicity from dietary phylloquinones and menaquinones has not been described. High doses of vitamin K can impair the actions of oral anticoagulants. See also Table 96e-2. See Chap. 423. Zinc is an integral component of many metalloenzymes in the body; it is involved in the synthesis and stabilization of proteins, DNA, and RNA and plays a structural role in ribosomes and membranes. Zinc is necessary for the binding of steroid hormone receptors and several other transcription factors to DNA. Zinc is absolutely required for normal spermatogenesis, fetal growth, and embryonic development. Absorption The absorption of zinc from the diet is inhibited by dietary phytate, fiber, oxalate, iron, and copper as well as by certain drugs, including penicillamine, sodium valproate, and ethambutol. Meat, shellfish, nuts, and legumes are good sources of bioavailable zinc, whereas zinc in grains and legumes is less available for absorption.


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InternalMed_Harrison. diseases, including diabetes mellitus, HIV/AIDS, cirrhosis, alcoholism, inflammatory bowel disease, malabsorption syndromes, and sickle cell disease. In these diseases, mild chronic zinc deficiency can cause stunted growth in children, decreased taste sensation (hypogeusia), and impaired immune function. Severe chronic zinc deficiency has been described as a cause of hypogonadism and dwarfism in several Middle Eastern countries. In these children, hypopigmented hair is also part of the syndrome. Acrodermatitis enteropathica is a rare autosomal recessive disorder characterized by abnormalities in zinc absorption. Clinical manifestations include diarrhea, alopecia, muscle wasting, depression, irritability, and a rash involving the extremities, face, and perineum. The rash is characterized by vesicular and pustular crusting with scaling and erythema. Occasional patients with Wilson’s disease have developed zinc deficiency as a consequence of penicillamine therapy (Chap. 429).


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InternalMed_Harrison. Zinc deficiency is prevalent in many developing countries and usually coexists with other micronutrient deficiencies (especially iron deficiency). Zinc (20 mg/d until recovery) may be an effective adjunctive therapeutic strategy for diarrheal disease and pneumonia in children ≥ 6 months of age. The diagnosis of zinc deficiency is usually based on a serum zinc level <12 μmol/L (<70 μg/dL). Pregnancy and birth control pills may cause a slight depression in serum zinc levels, and hypoalbuminemia from any cause can result in hypozincemia. In acute stress situations, zinc may be redistributed from serum into tissues. Zinc deficiency may be treated with 60 mg of elemental zinc taken by mouth twice a day. Zinc gluconate lozenges (13 mg of elemental zinc every 2 h while awake) have been reported to reduce the duration and symptoms of the common cold in adults, but study results are conflicting.


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InternalMed_Harrison. 96e-10 Toxicity Acute zinc toxicity after oral ingestion causes nausea, vomiting, and fever. Zinc fumes from welding may also be toxic and cause fever, respiratory distress, excessive salivation, sweating, and headache. Chronic large doses of zinc may depress immune function and cause hypochromic anemia as a result of copper deficiency. Intranasal zinc preparations should be avoided because they may lead to irreversible damage of the nasal mucosa and anosmia.


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InternalMed_Harrison. Copper is an integral part of numerous enzyme systems, including amine oxidases, ferroxidase (ceruloplasmin), cytochrome c oxidase, superoxide dismutase, and dopamine hydroxylase. Copper is also a component of ferroprotein, a transport protein involved in the basolateral transfer of iron during absorption from the enterocyte. As such, copper plays a role in iron metabolism, melanin synthesis, energy production, neurotransmitter synthesis, and CNS function; the synthesis and cross-linking of elastin and collagen; and the scavenging of superoxide radicals. Dietary sources of copper include shellfish, liver, nuts, legumes, bran, and organ meats.


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InternalMed_Harrison. Deficiency Dietary copper deficiency is relatively rare, although it has been described in premature infants who are fed milk diets and in infants with malabsorption (Table 96e-2). Copper-deficiency anemia (refractory to therapeutic iron) has been reported in patients with malabsorptive diseases and nephrotic syndrome and in patients treated for Wilson’s disease with chronic high doses of oral zinc, which can interfere with copper absorption. Menkes kinky hair syndrome is an X-linked metabolic disturbance of copper metabolism characterized by mental retardation, hypocupremia, and decreased circulating ceruloplasmin (Chap. 427). This syndrome is caused by mutations in the copper-transporting ATP7A gene. Children with this disease often die within 5 years because of dissecting aneurysms or cardiac rupture. Aceruloplasminemia is a rare autosomal recessive disease characterized by tissue iron overload, mental deterioration, microcytic anemia, and low serum iron and copper concentrations.


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InternalMed_Harrison. The diagnosis of copper deficiency is usually based on low serum levels of copper (<65 μg/dL) and low ceruloplasmin levels (<20 mg/ dL). Serum levels of copper may be elevated in pregnancy or stress conditions since ceruloplasmin is an acute-phase reactant and 90% of circulating copper is bound to ceruloplasmin. Toxicity Copper toxicity is usually accidental (Table 96e-2). In severe cases, kidney failure, liver failure, and coma may ensue. In Wilson’s disease, mutations in the copper-transporting ATP7B gene lead to accumulation of copper in the liver and brain, with low blood levels due to decreased ceruloplasmin (Chap. 429).


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InternalMed_Harrison. Selenium, in the form of selenocysteine, is a component of the enzyme glutathione peroxidase, which serves to protect proteins, cell membranes, lipids, and nucleic acids from oxidant molecules. As such, selenium is being actively studied as a chemopreventive agent against certain cancers, such as prostate cancer. Selenocysteine is also found in the deiodinase enzymes, which mediate the deiodination of thyroxine to triiodothyronine (Chap. 405). Rich dietary sources of selenium include seafood, muscle meat, and cereals, although the selenium content of cereal is determined by the soil concentration. Countries with low soil concentrations include parts of Scandinavia, China, and New Zealand. Keshan disease is an endemic cardiomyopathy found in children and young women residing in regions of China where dietary intake of selenium is low (<20 μg/d). Concomitant deficiencies of iodine and selenium may worsen the clinical manifestations of cretinism. Chronic ingestion of large amounts of


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InternalMed_Harrison. of China where dietary intake of selenium is low (<20 μg/d). Concomitant deficiencies of iodine and selenium may worsen the clinical manifestations of cretinism. Chronic ingestion of large amounts of selenium leads to selenosis, characterized by hair and nail brittleness and loss, garlic breath odor, skin rash, myopathy, irritability, and other abnormalities of the nervous system.


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InternalMed_Harrison. Chromium potentiates the action of insulin in patients with impaired glucose tolerance, presumably by increasing insulin receptor– mediated signaling, although its usefulness in treating type 2 diabetes is uncertain. In addition, improvement in blood lipid profiles has been reported in some patients. The usefulness of chromium supplements in muscle building has not been substantiated. Rich food sources of chromium include yeast, meat, and grain products. Chromium in the trivalent state is found in supplements and is largely nontoxic; however, chromium-6 is a product of stainless steel welding and is a known pulmonary carcinogen as well as a cause of liver, kidney, and CNS damage. See Chap. 423. FLuOrIDE, MANgANESE, AND uLTrATrACE ELEMENTS


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InternalMed_Harrison. See Chap. 423. FLuOrIDE, MANgANESE, AND uLTrATrACE ELEMENTS An essential function for fluoride in humans has not been described, although it is useful for the maintenance of structure in teeth and bones. Adult fluorosis results in mottled and pitted defects in tooth enamel as well as brittle bone (skeletal fluorosis). Manganese and molybdenum deficiencies have been reported in patients with rare genetic abnormalities and in a few patients receiving prolonged total parenteral nutrition. Several manganese-specific enzymes have been identified (e.g., manganese superoxide dismutase). Deficiencies of manganese have been reported to result in bone demineralization, poor growth, ataxia, disturbances in carbohydrate and lipid metabolism, and convulsions.


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InternalMed_Harrison. Ultratrace elements are defined as those needed in amounts <1 mg/d. Essentiality has not been established for most ultratrace elements, although selenium, chromium, and iodine are clearly essential (Chap. 405). Molybdenum is necessary for the activity of sulfite and xanthine oxidase, and molybdenum deficiency may result in skeletal and brain lesions.


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InternalMed_Harrison. 459 CHAPTER 97 Malnutrition and Nutritional Assessment Douglas C. Heimburger Malnutrition can arise from primary or secondary causes, result-ing in the former case from inadequate or poor-quality food intake and in the latter case from diseases that alter food intake or nutri-97 ent requirements, metabolism, or absorption. Primary malnutrition occurs mainly in developing countries and under conditions of political unrest, war, or famine. Secondary malnutrition, the main form encountered in industrialized countries, was largely unrecognized until the early 1970s, when it was appreciated that persons with adequate food supplies can become malnourished as a result of acute or chronic diseases that alter nutrient intake or metabolism, particularly diseases that cause acute or chronic inflammation. Various studies have shown that protein-energy malnutrition (PEM) affects one-third to one-half of patients on general medical and surgical wards in teaching hospitals. The consistent finding


InternalMed_Harrison

InternalMed_Harrison. Various studies have shown that protein-energy malnutrition (PEM) affects one-third to one-half of patients on general medical and surgical wards in teaching hospitals. The consistent finding that nutritional status influences patient prognosis underscores the importance of preventing, detecting, and treating malnutrition.


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InternalMed_Harrison. Definitions for forms of PEM are in flux. Traditionally, the two major types of PEM have been marasmus and kwashiorkor. These conditions are compared in Table 97-1. Marasmus is the end result of a long-term deficit of dietary energy, whereas kwashiorkor has been understood to result from a protein-poor diet. Although the former concept remains essentially correct, evidence is accumulating that PEM syndromes are distinguished by two main features: insufficient dietary intake and underlying inflammatory processes. Energy-poor diets with minimal inflammation cause gradual erosion of body mass, resulting in classic marasmus. By contrast, inflammation from acute illnesses such as injury or sepsis or from chronic illnesses such as cancer, lung or heart disease, or HIV infection can erode lean body mass even in the presence of relatively sufficient dietary intake, leading to a kwashiorkor-like state. Quite often, inflammatory illnesses impair appetite and dietary intake, producing


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InternalMed_Harrison. lean body mass even in the presence of relatively sufficient dietary intake, leading to a kwashiorkor-like state. Quite often, inflammatory illnesses impair appetite and dietary intake, producing combinations of the two conditions.


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InternalMed_Harrison. Consensus committees have proposed the following revised definitions. Starvation–related malnutrition is suggested for instances of chronic starvation without inflammation, chronic disease–related malnutrition when inflammation is chronic and of mild to moderate degree, and acute disease– or injury–related malnutrition when inflammation is acute and of a severe degree. However, because distinguishing diagnostic criteria for these conditions have not been universally adopted, this chapter integrates the older and newer terms.


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InternalMed_Harrison. Marasmus (starvation–related malnutrition) is a state in which virtually all available body fat stores have been exhausted due to starvation without systemic inflammation. Cachexia (chronic disease–related malnutrition) is a state that involves substantial loss of lean body mass in the presence of chronic systemic inflammation. Conditions that produce cachexia tend to be chronic and indolent, such as cancer and chronic pulmonary disease, whereas, in high-income countries, the classic setting for marasmus is in patients with anorexia nervosa. These conditions are relatively easy to detect because of the patient’s starved aThe findings used to diagnose kwashiorkor/acute malnutrition must be unexplained by other causes. bTested by firmly pulling a lock of hair from the top (not the sides or back), grasping with the thumb and forefinger. An average of three or more hairs removed easily and painlessly is considered abnormal hair pluckability.


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InternalMed_Harrison. appearance. The diagnosis is based on fat and muscle wastage resulting from prolonged calorie deficiency and/or inflammation. Diminished skinfold thickness reflects the loss of fat reserves; reduced arm muscle circumference with temporal and interosseous muscle wasting reflects the catabolism of protein throughout the body, including in vital organs such as the heart, liver, and kidneys. Routine laboratory findings in cachexia/marasmus are relatively unremarkable. The creatinine-height index (24-h urinary creatinine excretion compared with normal values based on height) is low, reflecting the loss of muscle mass. Occasionally, the serum albumin level is reduced, but it remains above 2.8 g/dL when systemic inflammation is absent. Despite a morbid appearance, immunocompetence, wound healing, and the ability to handle short-term stress are reasonably well preserved in most patients.


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InternalMed_Harrison. Pure starvation–related malnutrition is a chronic, fairly well adapted form of starvation rather than an acute illness; it should be treated cautiously in an attempt to reverse the downward trend gradually. Although nutritional support is necessary, overly aggressive repletion can result in severe, even life-threatening metabolic imbalances such as hypophosphatemia and cardiorespiratory failure (refeeding syndrome). When possible, oral or enteral nutritional support is preferred; treatment started slowly allows readaptation of metabolic and intestinal functions (Chap. 98e).


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InternalMed_Harrison. By contrast, kwashiorkor (acute disease– or injury–related malnutrition) in developed countries occurs mainly in connection with acute, life-threatening conditions such as trauma and sepsis. The physiologic stress produced by these illnesses increases protein and energy requirements at a time when intake is often limited. A classic scenario is an acutely stressed patient who receives only 5% dextrose solutions for periods as brief as 2 weeks. Although the etiologic mechanisms are not fully known, the protein-sparing response normally seen in starvation is blocked by the stressed state and by carbohydrate infusion.


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InternalMed_Harrison. In its early stages, the physical findings of kwashiorkor/acute malnutrition are few and subtle. Initially unaffected fat reserves and muscle mass give the deceptive appearance of adequate nutrition. Signs that support the diagnosis include easy hair pluckability, edema, skin breakdown, and poor wound healing. The major sine qua non is severe reduction of levels of serum proteins such as albumin (<2.8 g/dL) and transferrin (<150 mg/dL) or of iron-binding capacity (<200 μg/dL). Cellular immune function is depressed, as reflected by lymphopenia (<1500 lymphocytes/μL in adults and older children) and lack of response to skin test antigens (anergy).


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InternalMed_Harrison. The prognosis of adult patients with full-blown kwashiorkor/acute malnutrition is not good even with aggressive nutritional support. Surgical wounds often dehisce (fail to heal), pressure sores develop, gastroparesis and diarrhea can occur with enteral feeding, the risk of gastrointestinal bleeding from stress ulcers is increased, host defenses are compromised, and death from overwhelming infection may occur despite antibiotic therapy. Unlike treatment of marasmus, therapy for kwashiorkor entails aggressive nutritional support to restore better metabolic balance rapidly (Chap. 98e). The metabolic characteristics and nutritional needs of hypermetabolic patients who are stressed from injury, infection, or chronic inflammatory illness differ from those of hypometabolic patients who are unstressed but chronically starved. In both cases, nutritional support is important, but misjudgments in selecting the appropriate approach may have serious adverse consequences.


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InternalMed_Harrison. The hypometabolic patient is typified by the relatively less stressed but mildly catabolic and chronically starved individual who, with time, will develop cachexia/marasmus. The hypermetabolic patient stressed from injury or infection is catabolic (experiencing rapid breakdown of body mass) and is at high risk for developing acute malnutrition/ kwashiorkor if nutritional needs are not met and/or the illness does not resolve quickly. As summarized in Table 97-2, the two states are distinguished by differing perturbations of metabolic rate, rates of protein breakdown (proteolysis), and rates of gluconeogenesis. These differences are mediated by proinflammatory cytokines and counter-regulatory hormones—tumor necrosis factor, interleukins 1 and 6, C-reactive protein, catecholamines (epinephrine and norepinephrine), glucagon, and cortisol—whose levels are relatively reduced in hypo-metabolic patients and increased in hypermetabolic patients. Although insulin levels are also elevated in


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InternalMed_Harrison. and norepinephrine), glucagon, and cortisol—whose levels are relatively reduced in hypo-metabolic patients and increased in hypermetabolic patients. Although insulin levels are also elevated in stressed patients, insulin resistance in the target tissues blocks insulin-mediated anabolic effects. Physiologic


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InternalMed_Harrison. Cytokines, catecholamines, ↓↑ glucagon, cortisol, insulin Metabolic rate, O2 consumption ↓↑ Proteolysis, gluconeogenesis ↓↑ Ureagenesis, urea excretion ↓↑ Fat catabolism, fatty acid utilization Relative ↑ Absolute ↑ Adaptation to starvation Normal Abnormal characteristics of patients at risk for chronic disease–related malnutrition are less predictable and likely represent a mixture of the two extremes depicted in Table 97-2. Metabolic rate In starvation and semistarvation, the resting metabolic rate falls between 10% and 30% as an adaptive response to energy restriction, slowing the rate of weight loss. By contrast, the resting metabolic rate rises in the presence of physiologic stress in proportion to the degree of the insult. The rate may increase by ~10% after elective surgery, 20–30% after bone fractures, 30–60% with severe infections such as peritonitis or gram-negative septicemia, and as much as 110% after major burns.


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InternalMed_Harrison. If the metabolic rate (energy requirement) is not matched by energy intake, weight loss results—slowly in hypometabolism and quickly in hypermetabolism. Losses of up to 10% of body mass are unlikely to be detrimental; however, greater losses in acutely ill hypermetabolic patients may be associated with rapid deterioration in body functions.


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InternalMed_Harrison. Protein Catabolism The rate of endogenous protein breakdown (catabolism) to supply energy needs normally falls during uncomplicated energy deprivation. After ~10 days of total starvation, an unstressed individual loses about 12–18 g of protein per day (equivalent to ~60 g of muscle tissue or ~2–3 g of nitrogen). In contrast, in injury and sepsis, protein breakdown accelerates in proportion to the degree of stress, reaching 30–60 g/d after elective surgery, 60–90 g/d with infection, 100–130 g/d with severe sepsis or skeletal trauma, and >175 g/d with major burns or head injuries. These losses are reflected by proportional increases in the excretion of urea nitrogen, the major by-product of protein breakdown.


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InternalMed_Harrison. Gluconeogenesis The major aim of protein catabolism during a state of starvation is to provide the glucogenic amino acids (especially alanine and glutamine) that serve as substrates for endogenous glucose production (gluconeogenesis) in the liver. In the hypometabolic/starved state, protein breakdown for gluconeogenesis is minimized, especially as ketones derived from fatty acids become the substrate preferred by certain tissues. In the hypermetabolic/stress state, gluconeogenesis increases dramatically and in proportion to the degree of the insult to increase the supply of glucose (the major fuel of reparation). Glucose is the only fuel that can be utilized by hypoxemic tissues (anaerobic glycolysis), white blood cells, and newly generated fibroblasts. Infusions of glucose partially offset a negative energy balance but do not significantly suppress the high rates of gluconeogenesis in catabolic patients. Hence, adequate supplies of protein are needed to replace the amino acids used


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InternalMed_Harrison. a negative energy balance but do not significantly suppress the high rates of gluconeogenesis in catabolic patients. Hence, adequate supplies of protein are needed to replace the amino acids used for this metabolic response.


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InternalMed_Harrison. In summary, a hypometabolic patient is adapted to starvation and conserves body mass through reduction of the metabolic rate and use of fat as the primary fuel (rather than glucose and its precursor amino acids). A hypermetabolic patient also uses fat as a fuel but rapidly breaks down body protein to produce glucose, with consequent loss of muscle and organ tissue and danger to vital body functions. The same illnesses and reductions in nutrient intake that lead to PEM often produce deficiencies of vitamins and minerals as well (Chap. 96e). Deficiencies of nutrients that are stored in small amounts (such as the water-soluble vitamins) occur because of loss through external secretions, such as zinc in diarrhea fluid or burn exudate, and are probably more common than is generally recognized.


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InternalMed_Harrison. Deficiencies of vitamin C, folic acid, and zinc are relatively common in sick patients. Signs of scurvy, such as corkscrew hairs on the lower extremities, are found frequently in chronically ill and/or alcoholic patients. The diagnosis can be confirmed by determination of plasma vitamin C levels. Folic acid intakes and blood levels are often less than optimal, even among healthy persons; with illness, alcoholism, poverty, or poor dentition, these deficiencies are common. Low blood zinc levels are prevalent in patients with malabsorption syndromes such as inflammatory bowel disease. Patients with zinc deficiency often exhibit poor wound healing, pressure ulcer formation, and impaired immunity. Thiamine deficiency is a common complication of alcohol-461 ism but may be prevented by therapeutic doses of thiamine in patients treated for alcohol abuse.


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InternalMed_Harrison. Patients with low plasma vitamin C levels usually respond to the doses in multivitamin preparations, but patients with deficiencies should be supplemented with 250–500 mg/d. Folic acid is absent from some oral multivitamin preparations; patients with deficiencies should be supplemented with ~1 mg/d. Patients with zinc deficiencies resulting from large external losses sometimes require oral supplementation with 220 mg of zinc sulfate one to three times daily. For these reasons, laboratory assessments of the micronutrient status of patients at high risk are desirable. Hypophosphatemia develops in hospitalized patients with remarkable frequency and generally results from rapid intracellular shifts of phosphate in underweight or alcoholic patients receiving intravenous glucose (Chap. 63). The adverse clinical sequelae are numerous; some, such as acute cardiopulmonary failure, are collectively called refeeding syndrome and can be life-threatening.


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InternalMed_Harrison. Many developing countries are still faced with high preva lences of the classic forms of PEM: marasmus and kwashior kor. Food insecurity, which characterizes many poor countries, prevents consistent dietary sufficiency and/or quality and leads to endemic or cyclic malnutrition. Factors threatening food security include marked seasonal variations in agricultural productivity (rainy season–dry season cycles), periodic droughts, political unrest or injustice, and disease epidemics (especially of HIV/AIDS). The coexistence of malnutrition and disease epidemics exacerbates the latter and increases complications and mortality rates, creating vicious cycles of malnutrition and disease.


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InternalMed_Harrison. As economic prosperity improves, developing countries have been observed to undergo an epidemiologic transition, a component of which has been termed the nutrition transition. As improved economic resources make greater dietary diversity possible, middle-income populations (e.g., in southern Asia, China, and Latin America) typically begin to adopt lifestyle habits of industrialized nations, with increased consumption of energy and fat and decreased levels of physical activity. These changes lead to rising levels of obesity, metabolic syndrome, diabetes, cardiovascular disease, and cancer, sometimes coexisting in populations with persistent undernutrition.


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InternalMed_Harrison. Micronutrient deficiencies also remain prevalent in many countries of the world, impairing functional status and productivity and increasing mortality rates. Vitamin A deficiency impairs vision and increases morbidity and mortality rates from infections such as measles. Mild to moderate iron deficiency may be prevalent in up to 50% of the world, resulting from poor dietary diversity coupled with periodic blood loss and pregnancies. Iodine deficiency remains prevalent, causing goiter, hypothyroidism, and cretinism. Zinc deficiency is endemic in many populations, producing growth retardation, hypogonadism, and dermatoses and impairing wound healing. Fortunately, public health supplementation programs have substantially improved vitamin A and zinc status in developing countries during the past two decades, reducing mortality rates from measles, diarrheal diseases, and other manifestations. However, with the advancing nutrition transition and a shift toward nutritionally related chronic


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InternalMed_Harrison. two decades, reducing mortality rates from measles, diarrheal diseases, and other manifestations. However, with the advancing nutrition transition and a shift toward nutritionally related chronic noncommunicable conditions, it is estimated that nutrition remains one of the three greatest contributors of risk for morbidity and mortality worldwide.


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InternalMed_Harrison. Because interactions between illness and nutrition are complex, many physical and laboratory findings reflect both underlying disease and nutritional status. Therefore, the nutritional evaluation of a patient requires an integration of history, physical examination, anthropometrics, and laboratory studies. This approach helps both to detect nutritional problems and to prevent the conclusion that isolated findings indicate nutritional problems when they do not. For example, hypoalbuminemia caused by an inflammatory illness does not necessarily indicate malnutrition. NuTRITIONAl DEfICIENCy: THE HIgH-RIsK PATIENT Underweight (body mass index <18.5) and/or recent loss of ≥10% of usual body mass Poor intake: anorexia, food avoidance (e.g., psychiatric condition), or NPOa status for more than ~5 days Protracted nutrient losses: malabsorption, enteric fistulas, draining abscesses or wounds, renal dialysis Hypermetabolic states: sepsis, protracted fever, extensive trauma or burns


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InternalMed_Harrison. Protracted nutrient losses: malabsorption, enteric fistulas, draining abscesses or wounds, renal dialysis Hypermetabolic states: sepsis, protracted fever, extensive trauma or burns Alcohol abuse or use of drugs with antinutrient or catabolic properties: glucocorticoids, antimetabolites (e.g., methotrexate), immunosuppressants, antitumor agents Impoverishment, isolation, advanced age aNil per os (nothing by mouth). Nutritional History Elicitation of a nutritional history is directed toward the identification of underlying mechanisms that put patients at risk for nutritional depletion or excess. These mechanisms include inadequate intake, impaired absorption, decreased utilization, increased losses, and increased requirements for nutrients. Individuals with the characteristics listed in Table 97-3 are at particular risk for nutritional deficiencies.


InternalMed_Harrison

InternalMed_Harrison. Individuals with the characteristics listed in Table 97-3 are at particular risk for nutritional deficiencies. Physical Examination Physical findings that suggest vitamin, mineral, and protein-energy deficiencies and excesses are outlined in Table 97-4. Most of the physical findings are not specific for individual nutrient deficiencies and must be integrated with historic, anthropometric, and laboratory findings. For example, follicular hyperkeratosis on the back of the arms is a fairly common, normal finding. However, if it is widespread in a person who consumes few fruits and vegetables and smokes regularly (increasing ascorbic acid requirements), vitamin C deficiency is likely. Similarly, easily pluck-able hair may be a consequence of chemotherapy but suggests acute malnutrition/kwashiorkor in a hospitalized patient who has poorly healing surgical wounds and hypoalbuminemia.


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InternalMed_Harrison. anthropometric Measurements Anthropometric measurements provide information on body muscle mass and fat reserves. The most practical and commonly used measurements are body weight, height, triceps skinfold (TSF), and midarm muscle circumference (MAMC). Body weight is one of the most useful nutritional parameters to follow in patients who are acutely or chronically ill. Unintentional weight loss during illness often reflects loss of lean body mass (muscle and organ tissue), especially if it is rapid and is not caused by diuresis. Such weight loss can be an ominous sign since it indicates use of vital body protein stores for metabolic fuel. The reference standard for normal body weight, body mass index (BMI: weight in kilograms divided by height, in meters, squared), is discussed in Chap. 416. BMI values <18.5 are considered underweight; <17, significantly underweight; and <16, severely wasted. Values of 18.5–24.9 are normal; 25–29.9, overweight; and ≥30, obese.


InternalMed_Harrison

InternalMed_Harrison. Measurement of skinfold thickness is useful for estimating body fat stores, because ~50% of body fat is normally located in the subcutaneous region. This measurement can also permit discrimination of fat mass from muscle mass. The triceps is a convenient site that is generally representative of the body’s overall fat level. A thickness <3 mm suggests virtually complete exhaustion of fat stores. The MAMC can be used to estimate skeletal muscle mass, calculated as follows: MAMC (cm) = upper arm circumference (cm) − [0.314 × TSF (mm)]


InternalMed_Harrison

InternalMed_Harrison. MAMC (cm) = upper arm circumference (cm) − [0.314 × TSF (mm)] Laboratory Studies A number of laboratory tests used routinely in clinical medicine can yield valuable information about a patient’s nutritional status if a slightly different approach to their interpretation is used. For example, abnormally low serum albumin levels, low total iron-binding capacity, and anergy may have a distinct explanation, but collectively they may represent kwashiorkor. In the clinical setting of a hypermetabolic, acutely ill patient who is edematous and has easily pluckable hair and inadequate protein intake, the diagnosis of acute malnutrition/kwashiorkor is clear-cut. Commonly used laboratory tests for assessing nutritional status are outlined in Table 97-5. The table also provides tips to avoid the assignment of nutritional significance to tests that may be abnormal for nonnutritional reasons.


InternalMed_Harrison

InternalMed_Harrison. Assessment of circulAting (viscerAl) proteins The serum proteins most commonly used to assess nutritional status include albumin, total iron-binding capacity (or transferrin), thyroxine-binding prealbumin (or transthyretin), and retinol-binding protein. Because they have different synthesis rates and half-lives (the half-life of serum albumin is ~21 days, whereas those of prealbumin and retinol-binding protein are ~2 days and ~12 h, respectively), some of these proteins reflect changes in nutritional status more quickly than do others. However, rapid fluctuations can also make shorter-half-life proteins less reliable.


InternalMed_Harrison

InternalMed_Harrison. Levels of circulating proteins are influenced by their rates of synthesis and catabolism, “third spacing” (loss into interstitial spaces), and, in some cases, external loss. Although an adequate intake of calories and protein is necessary for optimal circulating protein levels, serum protein levels generally do not reflect protein intake. For example, a drop in the serum level of albumin or transferrin often accompanies significant physiologic stress (e.g., from infection or injury) and is not necessarily an indication of malnutrition or poor intake. A low serum albumin level in a burned patient with both hypermetabolism and increased dermal losses of protein may not indicate malnutrition. However, adequate nutritional support of the patient’s calorie and protein needs is critical for returning circulating proteins to normal levels as stress resolves. Thus low values by themselves do not define malnutrition, but they often point to increased risk of malnutrition because of the


InternalMed_Harrison

InternalMed_Harrison. for returning circulating proteins to normal levels as stress resolves. Thus low values by themselves do not define malnutrition, but they often point to increased risk of malnutrition because of the hypermetabolic stress state. As long as significant physiologic stress persists, serum protein levels remain low, even with aggressive nutritional support. However, if the levels do not rise after the underlying illness improves, the patient’s protein and calorie needs should be reassessed to ensure that intake is sufficient.


InternalMed_Harrison

InternalMed_Harrison. Assessment of vitAmin And minerAl stAtus The use of laboratory tests to confirm suspected micronutrient deficiencies is desirable because the physical findings for those deficiencies are often equivocal or nonspecific. Low blood micronutrient levels can predate more serious clinical manifestations and also may indicate drug-nutrient interactions. A patient’s basal energy expenditure (BEE, measured in kilocalories per day) can be estimated from height, weight, age, and sex with the Harris-Benedict equations: Men: BEE = 66.47 + 13.75W + 5.00H − 6.76A Women: BEE = 655.10 + 9.56W + 1.85H − 4.68A


InternalMed_Harrison

InternalMed_Harrison. Men: BEE = 66.47 + 13.75W + 5.00H − 6.76A Women: BEE = 655.10 + 9.56W + 1.85H − 4.68A In these equations, W is weight in kilograms, H is height in centimeters, and A is age in years. After these equations are solved, total energy requirements are estimated by multiplying BEE by a factor that accounts for the stress of illness. Multiplying by 1.1–1.4 yields a range 10–40% above basal that estimates the 24-h energy expenditure of the majority of patients. The lower value (1.1) is used for patients without evidence of significant physiologic stress; the higher value (1.4) is appropriate for patients with marked stress such as sepsis or trauma. The result is used as a 24-h energy goal for feeding.


InternalMed_Harrison

InternalMed_Harrison. When it is important to have a more accurate assessment, energy expenditure can be measured at the bedside by indirect calorimetry. This technique is useful in patients who are thought to be hypermetabolic from sepsis or trauma and whose body weight cannot be ascertained accurately. Indirect calorimetry can also be useful in patients who have difficulty weaning from a ventilator and whose energy needs therefore should not be exceeded to avoid excessive CO2 production. Patients at the extremes of weight (e.g., obese persons) and/or age are good candidates as well, because the Harris-Benedict equations were developed from measurements in adults with roughly normal body weights. Because urea is a major by-product of protein catabolism, the amount of urea nitrogen excreted each day can be used to estimate the rate of protein catabolism and determine whether protein intake is adequate to


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InternalMed_Harrison. Edema Heart failure Hepatomegaly Parotid enlargement Sudden heart failure, death offset it. Total protein loss and protein balance can be calculated from urinary urea nitrogen (UUN) as follows: Protein catabolic rate (g/d) = [24-h UUN (g) + 4] × 6.25 (g protein/g nitrogen) The value of 4 g added to the UUN represents a liberal estimate of the unmeasured nitrogen lost in the urine (e.g., creatinine and uric acid), sweat, hair, skin, and feces. When protein intake is low (e.g., less than


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InternalMed_Harrison. Thiamine; acute malnutrition Thiamine (“wet” beriberi), phosphorus Acute malnutrition Vitamin A Acute malnutrition (consider also bulimia) Vitamin C ~20 g/d), the equation indicates both the patient’s protein requirement and the severity of the catabolic state (Table 97-5). More substantial protein intakes can raise the UUN because some of the ingested (or intravenously infused) protein is catabolized and converted to UUN. Thus, at lower protein intakes, the equation is useful for estimating requirements, and at higher protein intakes it is useful for assessing protein balance. Causes of Normal Value Test (Normal Values) Nutritional Use Despite Malnutrition Other Causes of Abnormal Value Serum albumin (3.5–5.5 g/dL) Serum prealbumin, also called transthyretin (20–40 mg/dL; lower in prepubertal children) Prothrombin time (2.0–15.5 s)


InternalMed_Harrison

InternalMed_Harrison. Serum albumin (3.5–5.5 g/dL) Serum prealbumin, also called transthyretin (20–40 mg/dL; lower in prepubertal children) Prothrombin time (2.0–15.5 s) Serum creatinine (0.6–1.6 mg/dL) 24-h urinary creatinine (500–1200 mg/d, standardized for height and sex) 24-h urinary urea nitrogen (UUN; <5 g/d; depends on level of protein intake) 2.8–3.5 g/dL: Protein depletion or systemic inflammation <2.8 g/dL: Possible acute malnutrition or severe inflammation 10–15 mg/dL: Mild protein depletion or inflammation 5–10 mg/dL: Moderate protein depletion or inflammation <5 mg/dL: Severe protein depletion or inflammation Increasing value reflects positive protein balance <200 μg/dL: Protein depletion or inflammatory state; Prolongation: vitamin K deficiency <0.6 mg/dL: Muscle wasting due to prolonged energy deficit Reflects muscle mass Low value: muscle wasting due to prolonged energy deficit


InternalMed_Harrison

InternalMed_Harrison. Prolongation: vitamin K deficiency <0.6 mg/dL: Muscle wasting due to prolonged energy deficit Reflects muscle mass Low value: muscle wasting due to prolonged energy deficit Determine level of catabolism (as long as protein intake is ≥10 g below calculated protein loss or <20 g total, and as long as carbohydrate intake has been at least 100 g) 5–10 g/d: Mild catabolism or normal fed state 10–15 g/d: Moderate catabolism >15 g/d: Severe catabolism loss (protein catabolic rate) = [24-h UUN (g) + 4] × 6.25. Adjustments required in burn patients and others with large nonurinary nitrogen losses and in patients with fluctuating levels of blood urea nitrogen (e.g., in renal failure) <8 mg/dL: Possibly inadequate protein intake 12–23 mg/dL: Possibly adequate protein intake >23 mg/dL: Possibly excessive protein intake If serum creatinine is normal, use BUN. If serum creatinine is elevated, use BUN/creatinine ratio. (Normal range is essentially the same as for BUN.)


InternalMed_Harrison

InternalMed_Harrison. If serum creatinine is elevated, use BUN/creatinine ratio. (Normal range is essentially the same as for BUN.) Infusion of albumin, fresh-frozen plasma, or whole blood Common: Infection and other stress, especially with poor protein intake Burns, trauma Congestive heart failure Fluid overload Severe liver disease Uncommon: Nephrotic syndrome Zinc deficiency Bacterial stasis/overgrowth of small intestine Similar to serum albumin Similar to serum albumin Despite muscle wasting: Renal failure Severe dehydration Severe liver disease Anabolic state Syndrome of inappropriate Despite poor protein intake: Renal failure (Use BUN/creatinine ratio.) Congestive heart failure Gastrointestinal hemorrhage


InternalMed_Harrison

InternalMed_Harrison. Enteral and Parenteral Nutrition Therapy Bruce R. Bistrian, L. John Hoffer, David F. Driscoll When correctly implemented, specialized nutritional support (SNS) plays a major and often life-saving role in medicine. SNS is used for 98e two main purposes: (1) to provide an appropriate nutritional substrate in order to maintain or replenish the nutritional status of patients unable to voluntarily ingest or absorb sufficient amounts of food, and (2) to maintain the nutritional and metabolic status of adequately nourished patients who are experiencing systemic hypercatabolic effects of severe inflammation, injury, or infection in the course of persistent critical illness. Patients with permanent major loss of intestinal length or function often require lifelong SNS. Many patients who require treatment in chronic-care facilities receive enteral SNS, most often because their voluntary food intake is deemed insufficient or because impaired chewing and swallowing create a high risk of


InternalMed_Harrison

InternalMed_Harrison. treatment in chronic-care facilities receive enteral SNS, most often because their voluntary food intake is deemed insufficient or because impaired chewing and swallowing create a high risk of aspiration pneumonia.


InternalMed_Harrison

InternalMed_Harrison. Enteral SNS is the provision of liquid formula meals through a tube placed into the gut. Parenteral SNS is the direct infusion of complete mixtures of crystalline amino acids, dextrose, triglyceride emulsions, and micronutrients into the bloodstream through a central venous catheter or (rarely in adults) via a peripheral vein. The enteral route is almost always preferred because of its relative simplicity and safety, its low cost, and the benefits of maintaining digestive, absorptive, and immunologic barrier functions of the gastrointestinal tract. Pliable, small-bore feeding tubes make placement relatively easy and acceptable to patients. Constant-rate infusion pumps increase the reliability of nutrient delivery. The chief disadvantage of enteral SNS is that many days may be required to meet the patient’s nutrient requirements.


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InternalMed_Harrison. For short-term use, the feeding tube can be placed via the nose into the stomach, duodenum, or jejunum. For long-term use, these sites may be accessed through the abdominal wall by endoscopic or surgical procedures. The chief disadvantage of tube feeding in acute illness is intolerance due to gastric retention, risk of vomiting, or diarrhea. The presence of severe coagulopathy is a relative contraindication to the insertion of a feeding tube. In adults, parenteral nutrition (PN) almost always requires aseptic insertion of a central venous catheter with a dedicated port. Many circumstances can delay or slow the progression of enteral SNS, whereas parenteral SNS can provide a complete substrate mix easily and promptly. This practical advantage is mitigated by the need to infuse relatively large fluid volumes and the real risk of inadvertent toxic overfeeding. APPROACH TO THE PATIENT:


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InternalMed_Harrison. Approximately one-fifth to one-quarter of patients in acute-care hospitals suffer from at least moderate protein-energy malnutrition (PEM), the defining features of which are malnutrition-induced weight loss and skeletal muscle atrophy. Usually, but not always, other features further compromise clinical responses; these features include a subnormal adipose tissue mass, with the accompanying adverse consequences of weakness, skin thinning, and breakdown; reduced ventilatory drive; ineffective cough; immunodeficiency; and impaired thermoregulation. Commonly, PEM is already present at the time of hospital admission and remains unimproved or worsens during the ensuing hospital stay. Common reasons for PEM worsening during hospitalization are refusal of food (because of anorexia, nausea, pain, or delirium), communication barriers, an unmet need for hand-feeding of patients with physical or sensory impairment, disordered or ineffective chewing or swallowing, and prolonged periods of


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InternalMed_Harrison. pain, or delirium), communication barriers, an unmet need for hand-feeding of patients with physical or sensory impairment, disordered or ineffective chewing or swallowing, and prolonged periods of physician-ordered fasting—all potentially


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InternalMed_Harrison. TAblE 98e-1 body MASS INdEx (bMI), MuSClE MASS, ANd PRoTEIN ENERgy MAlNuTRITIoN (PEM) taking place in a context of caregiver unawareness and inattention. Most patients who are suffering from in-hospital PEM do not, or ought not, to require SNS. A large proportion of these patients can be expected to improve with appropriate management of their primary disease. Others have a terminal disease whose downward course will not be altered by SNS. In yet other cases, the PEM is sufficiently mild that the benefits of SNS are exceeded by its risks. For patients who fall into this last category, the correct approach is to intensify and/or modify the patient’s oral nutrition as directed by the unit dietitian.


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InternalMed_Harrison. PEM is often classified as minimal, moderate, or severe on the basis of weight for height (body mass index, BMI) and percentage of body weight recently lost. As shown in Table 98e-1, the BMI (when corrected for abnormal extracellular fluid accumulation) is a crude but useful indicator of PEM severity. Note, however, that obesity does not preclude moderate or severe PEM, especially in older or bedridden patients; indeed, obesity can mask the presence of PEM if the patient’s muscle mass is not specifically examined.


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InternalMed_Harrison. The decision to implement SNS must be based on the determinations (1) that intensified or modified oral nutrition has failed or is impossible, impractical, or undesirable; and (2) that SNS will increase the patient’s rate and likelihood of recovery, reduce the risk of infection, improve healing, or otherwise shorten the hospital stay. In chronic-care situations, the decision to institute SNS is based on the likelihood that the intervention will extend the duration or quality of the patient’s life. An algorithm for determining when to use SNS is depicted in Fig. 98e-1. The decision to enhance oral nutrition or—that attempt failing— to resort to SNS is based on the anticipated consequences of nonintervention. The mnemonic “in-in-in” (for inanition-inflammation-inactivity) can serve as a reminder of the three main factors that come into play when deciding whether or not it is acceptable to withhold SNS from a patient with PEM.


InternalMed_Harrison

InternalMed_Harrison. Inanition Key issues include whether normal food intake is likely to be impossible for a prolonged period and whether the patient can tolerate prolonged starvation. A previously well-nourished person can tolerate ~7 days of starvation without harm, even in the presence of a moderate systemic response to inflammation (SRI), whereas the degree of tolerance to prolonged starvation is much less in patients whose skeletal muscle mass is already reduced, whether from PEM, from the muscle atrophy of old age (sarcopenia), or from muscle atrophy due to neuromuscular disease. Excess body fat does not exclude the possibility of coexisting muscle atrophy from any of these causes. In general, unintentional weight loss of >10% during the previous 6 months or a weight-to-height ratio that is <90% of standard, when associated with physiologic impairment, crudely predicts that the patient has moderate PEM. Weight loss >20% of usual or <80% of standard makes severe PEM more likely.


InternalMed_Harrison

InternalMed_Harrison. Inflammation The anorexia that invariably accompanies the SRI reduces the likelihood that a patient’s nutritional goals will be achieved by intensifying or modifying the diet, by providing counseling, or by hand-feeding. Furthermore, the protein-catabolic


InternalMed_Harrison

InternalMed_Harrison. Is disease process likely to cause nutritional impairment? Does the patient have PCM or is at risk for PCM? Would preventing or treating the malnutrition with SNS improve the prognosis and quality of life? What are the fluid, energy, mineral, and vitamin requirements and can these be provided enterally? Does the patient require total parenteral nutrition? Can requirements be met through oral foods and liquid supplements? Keep under surveillance with frequent calorie counts and clinical assessment Request feeding tube Needed for several weeks Needed for months or years Nasally inserted tube Percutaneously inserted tube Request CVC, PICC or peripheral catheter plus enteral nutrition Request CVC or PICC Need for several weeks Need for months or years Tunneled external catheter or subcutaneous infusion port Subclavian catheter or PICC Risks and discomfort of SNS outweigh potential benefits. Explain issue to patient or legal surrogate. Support patient


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InternalMed_Harrison. catheter or subcutaneous infusion port Subclavian catheter or PICC Risks and discomfort of SNS outweigh potential benefits. Explain issue to patient or legal surrogate. Support patient with general comfort measures including oral food and liquid supplements if desired. Yes Yes Yes No Yes Yes Yes No No No


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InternalMed_Harrison. FIgURE 98e-1 Decision-making for the implementation of specialized nutritional support (SNS). CVC, central venous catheter; PICC, peripherally inserted central catheter. (Adapted from the chapter on this topic in Harrison’s Principles of Internal Medicine, 16e, by Lyn Howard, MD.) effects of the SRI accelerate skeletal muscle wasting and substantially block normal protein-sparing adaptation to protein and energy starvation. Inactivity A nutritional red flag should be raised over every acutely ill patient who remains bedridden or inactive for a prolonged period. Such patients commonly manifest muscle atrophy (due to nutritional deficiencies and disuse) and anorexia with inadequate voluntary food intake.


InternalMed_Harrison

InternalMed_Harrison. Once it has been determined that a patient has significant— and, in particular, progressive—PEM despite meaningful efforts to reverse it by modifying the diet or the way food is provided, the next step is to decide whether SNS will have a net positive effect on the patient’s clinical outcome. The pathway to the end stage of most severe chronic diseases leads through PEM. In most patients with end-stage untreatable cancer or certain end-organ diseases, SNS will neither reverse PEM nor improve the quality of life. Provision of food and water is commonly regarded as an aspect of basic humane care; in contrast, enteral and parenteral SNS is a therapeutic intervention that can cause discomfort and pose risks. As with other life-support interventions, the discontinuation of enteral or parenteral SNS can be psychologically difficult for patients, their families, and their caregivers. Indeed, the difficulty can be greater with SNS than with other life-support interventions because the


InternalMed_Harrison

InternalMed_Harrison. SNS can be psychologically difficult for patients, their families, and their caregivers. Indeed, the difficulty can be greater with SNS than with other life-support interventions because the provision of food and water is often considered equivalent to comfort care. In such difficult, near end-of-life situations, it is prudent to explicitly state the treatment goals at the outset of a course of SNS therapy. Such clarity can smooth the way for subsequent appropriate discontinuation in those patients whose prognosis has become hopeless.


InternalMed_Harrison

InternalMed_Harrison. After the decision has been made that SNS is indeed appropriate, the next determinations are the route of delivery (enteral versus parenteral), timing, and calculation of the patient’s nutritional goals. Although enteral SNS is the default option, the choice of optimal route depends on the degree of gut function as well as on available technical resources. Both the choice of route and the timing of SNS require an evaluation of the patient’s current nutritional status, the presence and extent of the SRI, and the anticipated clinical course. Severe SRI is identified on the basis of the standard clinical signs of leukocytosis, tachycardia, tachypnea, and temperature elevation or depression.


InternalMed_Harrison

InternalMed_Harrison. Serum albumin is a negative acute-phase protein and hence a marker of the SRI. More severe hypoalbuminemia is a crude indicator of greater SRI severity, but this condition is almost certainly worsened by concurrent dietary protein deficiency. Despite the importance of adequate protein provision to patients with the SRI, no amount of SNS will raise serum albumin levels into the normal range as long as the SRI persists. The SRI can be graded as mild, moderate, or severe. Examples of a severe SRI include (1) sepsis or other major inflammatory diseases (e.g., pancreatitis) that require care in the intensive care unit; (2) multiple trauma with an Injury Severity Score >20–25 or an Acute Physiology and Chronic Health Evaluation II (APACHE


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InternalMed_Harrison. II) score >25; (3) closed head injury with a Glasgow Coma Scale <8; and (4) major third-degree burns of >40% of the body surface area. A moderate SRI occurs with less severe infections, injuries, or inflammatory conditions like pneumonia, uncomplicated major surgery, acute hepatic or renal injury, and exacerbations of ulcerative colitis or regional enteritis requiring hospitalization.


InternalMed_Harrison

InternalMed_Harrison. Patients with a severe SRI require the initiation of SNS within the first several days of care, for they are highly unlikely to consume an adequate amount of food voluntarily over the next 7 days. On the other hand, a moderate SRI, as is common during the period following major uncomplicated surgery without oral intake, may be tolerated for 5–7 days as long as the patient is initially well nourished. Patients awaiting elective major surgery benefit from preoperative nutritional repletion for 5–10 days but only in the presence of significant PEM. When adequate preoperative nutrition or SNS is impractical, early postoperative SNS is usually indicated. Furthermore, patients with a combination of a moderate SRI and moderate PEM are likely to benefit from early postoperative SNS.


InternalMed_Harrison

InternalMed_Harrison. The risks of enteral SNS are determined primarily by the patient’s state of alertness and swallowing competence, the anatomy and function of the gastrointestinal tract, and the experience of the supervising clinical team. The safest and least costly approach is to avoid SNS by close attention to oral food intake; personal encouragement; dietary modifications; hand-feeding, when possible; and, often, the addition of an oral liquid supplement. For this reason, all patients at nutritional risk should be assessed and followed by a nutritionist. There is increasing interest in the use, under selected circumstances and when not contraindicated, of pharmacologic doses of anabolic steroids to stimulate appetite and promote muscle anabolism.


InternalMed_Harrison

InternalMed_Harrison. Nasogastric tube insertion is a bedside procedure, but many critically ill patients have impaired gastric emptying and a high risk of aspiration pneumonia. This risk can be reduced by placing the tip of the feeding tube in the jejunum beyond the ligament of Treitz, a procedure that usually requires fluoroscopic or endoscopic guidance. When a laparotomy is planned for a patient who has other surgical conditions likely to necessitate prolonged SNS, it is advantageous to place a jejunal feeding tube at the time of surgery. A major disadvantage of enteral SNS is that the amounts of protein and calories provided to critically ill patients commonly fail to reach target goals within the first 7–14 days after SNS is initiated. This problem is compounded by the lack of enteral products that allow the provision of the recommended protein target of 1.5–2.0 g/kg without simultaneously inducing potentially harmful caloric overfeeding.


InternalMed_Harrison

InternalMed_Harrison. Enteral SNS is often required in patients with anorexia, impaired swallowing, or small-intestinal disease. The bowel and its associated digestive organs derive 70% of their required nutrients directly from nutritional substrates absorbed from the intestinal lumen. Enteral feeding also supports gut function by stimulating splanchnic blood flow, neuronal activity, IgA antibody release, and secretion of gastrointestinal hormones that stimulate gut trophic activity. These factors support the gut as an immunologic barrier against enteric pathogens. For these reasons, current evidence indicates that some luminal nutrition should be provided, even when PN is required to provide most of the nutritional support. The nonessential amino acids arginine and glutamine, short-chain fatty acids, long-chain omega 3 fatty acids, and nucleotides are available in some specialty enteral formulas and appear to have an important role in maintaining immune function. The addition of supplemental PN to enteral


InternalMed_Harrison

InternalMed_Harrison. omega 3 fatty acids, and nucleotides are available in some specialty enteral formulas and appear to have an important role in maintaining immune function. The addition of supplemental PN to enteral feeding (either by mouth or as SNS by enteral tube) may hasten the transition to full enteral feeding, which is usually successful when >50% of requirements can be met enterally. As long as protein and other essential nutrient requirements are met, substantial nutritional benefit can be achieved by providing ~50% of energy needs for periods of up to 10 days. As a rule of thumb, dietary protein provision should be increased by ~25–50% when energy intake is reduced by this amount, since negative energy balance reduces the efficiency of dietary protein retention. For longer periods and in patients who have a normal or increased body fat content, it may be preferable to provide only 75–80% of energy needs (together with increased protein), as the mild energy deficit improves gastrointestinal


InternalMed_Harrison

InternalMed_Harrison. who have a normal or increased body fat content, it may be preferable to provide only 75–80% of energy needs (together with increased protein), as the mild energy deficit improves gastrointestinal tolerance, makes glycemic control far easier, and avoids excess fluid administration.


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InternalMed_Harrison. The main risks of PN are related to the placement of a central venous catheter, with its complications of thrombosis and infection, and the relatively large intravenous volumes infused. Less often appreciated are the risks associated with the ease of inadvertently infusing excessive carbohydrate and lipid directly into the bloodstream. These risks include hyperglycemia, inadequate lipid clearance from the circulation, hepatic steatosis and inflammation, and even respiratory failure in patients with borderline pulmonary function. On the other hand, renal dysfunction does not reduce a patient’s requirement for protein or amino acids. In cases in which renal function is a limiting factor, appropriate renal replacement therapy must be provided along with SNS.


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InternalMed_Harrison. In the past, bowel rest through PN was the cornerstone of treatment for many severe gastrointestinal disorders. However, the value of providing even minimal amounts of enteral nutrition (EN) is now widely accepted. Protocols to facilitate more widespread use of EN include initiation within 24 h of ICU admission; aggressive use of the head-upright position; use of postpyloric and nasojejunal feeding tubes; use of prokinetic agents; more rapid increases in feeding rates; tolerance of higher gastric residuals; and adherence to nurse-directed algorithms for feeding progression. Parenteral SNS alone is generally necessary only for severe gut dysfunction due to prolonged ileus, intestinal obstruction, or severe hemorrhagic pancreatitis.


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InternalMed_Harrison. In critically ill patients, parenteral SNS can be commenced within the first 24 h of care, with the anticipation of a better clinical outcome and a lower mortality risk than those following delayed or inadequate enteral SNS; however, this point remains controversial. Some evidence suggests that early SNS is associated with a reduced risk of death but also with an increased risk of serious infection. More recent data, obtained in studies of moderately critically ill patients, suggest that early hypocaloric parenteral SNS lessens morbidity and mitigates muscle atrophy without an increased risk of infection, but also without a detectable reduction in mortality risk. Unfortunately, the current clinical-trial evidence fails to address several important unknowns. It is important to note that the level of protein substrate provided in published clinical trials generally falls well below the current recommendation, even in trials of supplemental parenteral SNS. Much of the increase in


InternalMed_Harrison

InternalMed_Harrison. that the level of protein substrate provided in published clinical trials generally falls well below the current recommendation, even in trials of supplemental parenteral SNS. Much of the increase in morbidity associated with parenteral and enteral SNS can be ascribed to hyperglycemia, which can be prevented by appropriately intensive insulin therapy. The level of glycemia necessary to prevent complications, whether <110 mg/dL or <150 mg/dL, remains unclear. Adequately fed surgical patients may benefit from the lower glucose range, but studies of intensive insulin therapy alone, without full feeding, suggest improved morbidity and mortality outcomes with looser control of glucose at <180 mg/dL.


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InternalMed_Harrison. In the early years of its use, PN was relatively expensive, but its components now are often less costly than specialty enteral formulas. Percutaneous placement of a central venous catheter into the subclavian vein or (less desirably) the internal jugular vein with advancement into the superior vena cava can be accomplished at the bedside by trained personnel using sterile techniques. Peripherally inserted central catheters (PICCs) can also be used, although they are usually more appropriate for non-ICU patients. Subclavian or internal jugular catheters carry the risks of pneumothorax or serious vascular damage but are generally well tolerated and, rather than requiring reinsertion, can be exchanged over a wire when catheter infection is suspected.


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InternalMed_Harrison. Although most SNS is delivered in hospitals, some patients require it on a long-term basis. At-home SNS requires a safe home environment, a stable clinical condition, and the patient’s ability and willingness to learn appropriate self-care techniques. Other important considerations in determining the appropriateness of at-home parenteral or enteral SNS are that the patient’s prognosis indicates survival for longer than several months and that the therapy enhances the patient’s quality of life.


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InternalMed_Harrison. The purpose of SNS is to correct and prevent malnutrition. Certain conditions require special modification of the SNS regimen. Protein intake may need to be limited in many stable patients with renal insufficiency or borderline liver function. In renal disease, except for brief periods, protein intakes should approach the required level for normal adults of at least 0.8 g/kg and should aim for 1.2 g/kg as long as severe azotemia does not occur. Patients with severe renal failure who require SNS need concurrent renal replacement therapy. In hepatic failure, protein intakes of 1.2–1.4 g/kg (up to 1.5 g/kg) should be provided as long as encephalopathy due to protein intolerance does not occur. In the presence of protein intolerance, formulas containing 33–50% branched-chain amino acids are available and can be provided at the 1.2to 1.4-g/kg level. Cardiac patients and many other severely stressed patients often benefit from fluid and sodium restriction to 1000 mL of PN formula and 5–20


InternalMed_Harrison

InternalMed_Harrison. available and can be provided at the 1.2to 1.4-g/kg level. Cardiac patients and many other severely stressed patients often benefit from fluid and sodium restriction to 1000 mL of PN formula and 5–20 meq of sodium per day. In patients with severe chronic PEM characterized by severe weight loss, it is important to initiate PN gradually because of the profound antinatriuresis, antidiuresis, and intracellular accumulation of potassium, magnesium, and phosphorus that develop as a consequence of the resulting high insulin levels. This modification of parenteral SNS is usually accomplished by limiting daily fluid intake initially to ~1000 mL; limiting carbohydrate intake to 10–20% dextrose; limiting sodium intake; and providing ample potassium, magnesium, and phosphorus, with careful daily assessment of fluid and electrolyte status. Protein need not be restricted.


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InternalMed_Harrison. Normal adults require ~30 mL of fluid/kg of body weight from all sources each day as well as the replacement of abnormal losses such as those caused by diuretic therapy, nasogastric tube drainage, wound output, high rates of perspiration (which can be several liters per day during periods of extreme heat), and diarrhea/ostomy losses. Electrolyte and mineral losses can be estimated or measured and need to be replaced (Table 98e-2). Fluid restriction may be necessary in patients with fluid overload. Total fluid input can usually be limited to 1200 mL/d as long as urine is the only significant source of fluid output. In severe fluid overload, a 1-L central vein PN solution of 7% crystalline amino acids (70 g) and 21% dextrose (210 g) can temporarily provide an acceptable amount of glucose and protein substrate in the absence of significant catabolic stress.


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InternalMed_Harrison. Patients who require PN or EN in the acute-care setting generally have associated hormonal adaptations to their underlying disease (e.g., increased secretion of antidiuretic hormone, aldosterone, insulin, glucagon, or cortisol), and these signals promote fluid retention and hyperglycemia. In critical illness, body weight is invariably increased due to fluid resuscitation and fluid retention. Lean-tissue accretion is minimal in the acute phase of critical illness, no matter how much protein and or how many calories are provided. Because excess fluid removal can be difficult, limiting fluid intake to allow for balanced intake and output is more effective.


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InternalMed_Harrison. Total energy expenditure comprises resting energy expenditure, activity energy expenditure, and the thermal effect of feeding (Chap. 97). Resting energy expenditure accounts for two-thirds of total energy expenditure, activity energy expenditure for one-fourth to one-third, and the thermal effect of feeding for ~10%. For normally nourished, healthy individuals, the total energy expenditure is ~30–35 kcal/kg. Critical illness increases resting energy expenditure, but this increase is significant only in initially well-nourished individuals with a robust SRI who experience, for example, severe multiple trauma, extensive burns, sepsis, sustained high fever, or closed head injury. In these situations, total energy expenditure can reach 40–45 kcal/kg. The chronically starved patient with adapted PEM has a reduced energy expenditure and is inactive, with a usual total energy expenditure of ~20–25 kcal/kg. Very few patients with adapted PEM require as much as 30 kcal/kg for energy balance.


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InternalMed_Harrison. PEM has a reduced energy expenditure and is inactive, with a usual total energy expenditure of ~20–25 kcal/kg. Very few patients with adapted PEM require as much as 30 kcal/kg for energy balance. Because providing ~50% of measured energy expenditure as SNS is at least as effective as 100% for the first 10 days of critical illness, actual measurement of energy expenditure generally is not necessary in the early period of SNS. However, in patients who remain critically ill beyond several weeks, in patients with severe PEM for whom estimates of energy expenditure are unreliable, and in patients who are difficult to wean from ventilators, it is reasonable to measure energy expenditure directly when the technique is available, targeting an energy intake of 100–120% of the measured energy expenditure.


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InternalMed_Harrison. Insulin resistance due to the SRI is associated with increased gluconeogenesis and reduced peripheral glucose utilization, with resulting hyperglycemia. Hyperglycemia is aggravated by excessive exogenous carbohydrate administration from SNS. In critically ill patients receiving SNS, normalization of blood glucose levels by insulin infusion reduces morbidity and mortality risk. In mildly or moderately malnourished patients, it is reasonable to provide metabolic support in order to improve protein synthesis and maintain metabolic homeostasis. Hypocaloric nutrition, with provision of ~1000 kcal and 70 g protein per day for up to 10 days, requires less fluid and reduces the likelihood of poor glycemic control, although a higher protein intake would be optimal. During the second week of SNS, energy and protein provision can be advanced to 20–25 kcal/kg and 1.5 g/kg per day, respectively, as metabolic conditions permit. As mentioned above, patients with multiple trauma, closed head injury,


InternalMed_Harrison

InternalMed_Harrison. and protein provision can be advanced to 20–25 kcal/kg and 1.5 g/kg per day, respectively, as metabolic conditions permit. As mentioned above, patients with multiple trauma, closed head injury, and severe burns often have greatly elevated energy expenditures, but there is little evidence that providing >30 kcal/kg daily confers further benefit, and such high caloric intake may well be harmful as it substantially increases the risk of hyperglycemia.


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InternalMed_Harrison. As a rule, amino acids and glucose are provided in an increasing dose until energy provision matches estimated resting energy expenditure. At this point, it becomes beneficial to add fat. A surfeit of glucose merely stimulates de novo lipogenesis—an energy-inefficient process. Polyunsaturated long-chain triglycerides (e.g., in soybean oil) are the chief ingredient in most parenteral fat emulsions and provide the majority of the fat in enteral feeding formulas. These vegetable oil–based emulsions provide essential fatty acids. The fat content of enteral feeding formulas ranges from 3% to 50% of energy. Parenteral fat is provided in separate containers as 20% and 30% emulsions that can be infused separately or mixed in the sterile pharmacy as an all-in-one or total nutrient admixture of amino acids, glucose, lipid, electrolytes, vitamins, and minerals. Although parenteral fat needs to make up only ~3% of the energy requirement in order to meet essential fatty acid requirements, when


InternalMed_Harrison

InternalMed_Harrison. amino acids, glucose, lipid, electrolytes, vitamins, and minerals. Although parenteral fat needs to make up only ~3% of the energy requirement in order to meet essential fatty acid requirements, when provided daily as an all-in-one mixture of carbohydrate, fat, and protein, the complete admixture has a fat content of 2–3 g/dL and provides 20–30% of the total energy requirement—an acceptable level that offers the advantage of ensuring emulsion stability. When given as a separate infusion, parenteral fat should not be provided at rates exceeding 0.11 g/kg of body mass or 100 g over 12 h—equivalent to 500 mL of 20% parenteral fat.


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InternalMed_Harrison. Medium-chain triglycerides containing saturated fatty acids with chain lengths of 6, 8, 10, or 12 carbons (>95% of which are C8 and C10) are included in a number of enteral feeding formulas because they are absorbed preferentially. Fish oil contains polyunsaturated fatty acids of the omega 3 family, which improve immune function and reduce the inflammatory response. At this time, fish oil injectable emulsions are available in the United States as an investigational new drug.


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InternalMed_Harrison. PN formulations provide carbohydrate as hydrous glucose (3.4 kcal/g). In enteral formulas, glucose is the carbohydrate source for so-called monomeric diets. These diets provide protein as amino acids and fat in minimal amounts (3%) to meet essential fatty acid requirements. Monomeric formulas are designed to optimize absorption in the seriously compromised gut. These formulas, like immune-enhancing diets, are expensive. In polymeric diets, the carbohydrate source is usually an osmotically less active polysaccharide, the protein is usually soy or casein protein, and fat is present at concentrations of 25–50%. Such formulas are usually well tolerated by patients with normal intestinal length, and some are acceptable for oral consumption.


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InternalMed_Harrison. The daily protein recommendation for healthy adults is 0.8 g/kg, but body proteins are replenished faster with 1.5 g/kg in patients with PEM, and net protein catabolism is reduced in critically ill patients when 1.5–2.0 g/kg is provided. In patients who are not critically ill but who require SNS in the acute-care setting, at least 1 g of protein/ kg is recommended, and larger amounts up to 1.5 g/kg are appropriate when volume, renal, and hepatic tolerances allow. The standard parenteral and enteral formulas contain protein of high biologic value and meet the requirements for the eight essential amino acids when nitrogen needs are met. Parenteral amino acid mixtures and elemental enteral mixtures consist of hydrated individual amino acids. Because of their hydrated status, elemental amino acid solutions deliver 17% less protein substrate than intact proteins. In protein-intolerant conditions such as renal and hepatic failure, modified amino acid formulas may be considered. In hepatic


InternalMed_Harrison

InternalMed_Harrison. acid solutions deliver 17% less protein substrate than intact proteins. In protein-intolerant conditions such as renal and hepatic failure, modified amino acid formulas may be considered. In hepatic failure, higher branched-chain, amino acid–enriched formulas appear to improve outcomes. Conditionally essential amino acids like arginine and glutamine may also have some benefit in supplemental amounts.


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InternalMed_Harrison. Protein (nitrogen) balance provides a measure of the efficacy of parenteral or enteral SNS. This balance is calculated as protein intake/6.25 (because proteins are, on average, 16% nitrogen) minus the 24-h urine urea nitrogen plus 4 g of nitrogen (the latter reflecting other nitrogen losses). In critical illness, a mild negative nitrogen balance of 2–4 g/d is often achievable. A similarly mild positive nitrogen balance is observed in the nonstressed recuperating patient. Each gram of nitrogen lost or gained represents ~30 g of lean tissue.


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InternalMed_Harrison. Parenteral electrolyte, vitamin, and trace mineral requirements are summarized in Tables 98e-3, 98e-4, and 98e-5, respectively. Electrolyte modifications are necessary with substantial gastrointestinal losses from nasogastric drainage or intestinal losses from fistulas, diarrhea, or ostomy outputs. Such losses also imply extra calcium, magnesium, and zinc losses. Zinc losses are high in secretory diarrhea. Secretory diarrhea contains ~12 mg of zinc/L, and patients with intestinal fistulas or chronic diarrhea require an average of ~12 mg of Acetate Calcium Magnesium Phosphorus 10 meq 10 meq 30 mmol 1–2 meq/kg + replacement, but can be as low as 5–40 meq/d 40–100 meq/d + replacement of unusual losses


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InternalMed_Harrison. Acetate Calcium Magnesium Phosphorus 10 meq 10 meq 30 mmol 1–2 meq/kg + replacement, but can be as low as 5–40 meq/d 40–100 meq/d + replacement of unusual losses As needed for acid-base balance, but usually 2:1 to 1:1 with acetate As needed for acid-base balance 10–20 meq/d 8–16 meq/d 20–40 mmol parenteral zinc/d (equivalent to 30 mg of oral elemental zinc) to maintain zinc balance. Excessive urinary potassium losses with amphotericin or magnesium losses with cisplatin or in renal failure necessitate adjustments in sodium, potassium, magnesium, phosphorus, and acid-base balance. Vitamin and trace element requirements are met by the daily provision of a complete parenteral vitamin supplement and trace elements via PN and by the provision of adequate amounts of enteral feeding formulas that contain these micronutrients.


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InternalMed_Harrison. Iron is a highly reactive catalyst of oxidative reactions and thus is not included in PN mixtures. The parenteral iron requirement is normally only ~1 mg/d. Iron deficiency occurs with considerable frequency in acutely ill hospitalized patients, especially those with PEM and gastrointestinal tract disease, and in patients subjected to frequent blood withdrawals. Iron deficiency is sometimes inadequately considered in hospitalized patients because there are commoner causes: the inflammation-mediated anemia of chronic disease (with an associated increase in serum ferritin, an acute-phase protein) and redistribution of the intravascular fluid volume during prolonged bed rest. Iron deficiency should be considered in every patient receiving SNS. A falling mean red cell volume, even if still in the low-normal range, together with an intermediate serum ferritin concentration is suggestive of iron deficiency. Intravenous iron infusions follow standard guidelines, always with a termination


InternalMed_Harrison

InternalMed_Harrison. in the low-normal range, together with an intermediate serum ferritin concentration is suggestive of iron deficiency. Intravenous iron infusions follow standard guidelines, always with a termination order and never as a standing order because of the risk of inadvertent iron overdosing. Major iron replacement during critical illness is of some concern because of the possibility that a substantial rise in the serum iron concentration may increase susceptibility to some bacterial infections.


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InternalMed_Harrison. 3.6 mg 40 mg 600 μg 15 mg 6 mg 5 μg 60 μg 200 mg 200 IUa 10 IU 150 μg aThe current vitamin D requirement—a minimum of 600 IU/day—cannot be met with available injectable vitamin formulations. Calcitriol is not equivalent to vitamin D and is not a suitable replacement for it, since it is not a substrate for 25-hydroxyvitamin D biosynthesis. bA product is available without vitamin K. Vitamin K supplementation is recommended at 2–4 mg/week in patients not receiving oral anticoagulation therapy when the vitamin K–free product is used. aCommercial products are available with the first four, the first five, and all seven of these metals in recommended amounts. bThe basal IV zinc requirement is approximately one-third of the oral requirement, because only approximately one-third of orally ingested zinc is absorbed. Abbreviation: PN, parenteral nutrition.


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InternalMed_Harrison. Parenteral feeding through a peripheral vein is limited by osmolarity and volume constraints. Solutions with an osmolarity >900 mOsm/L (e.g., those which contain >3% amino acids and 5% glucose [290 kcal/L]) are poorly tolerated peripherally. Parenteral lipid emulsions (20%) can be given to increase the calories delivered. The total volume required for a marginal amino acid provision rate of 60 g (equivalent to 50 g of protein) and a total of 1680 kcal is 2.5 L. Moreover, the risk of significant morbidity and mortality from incompatibilities of calcium and phosphate salts is greatest in these low-osmolarity, low-glucose regimens. For short-term infusions, calcium may be temporarily limited or even omitted from the mixture. Parenteral feeding via a peripheral vein is generally intended as a supplement to oral feeding; it is not suitable for the critically ill. Peripheral PN may be enhanced by small amounts of heparin (1000 U/L) and co-infusion with parenteral fat to reduce osmolarity,


InternalMed_Harrison

InternalMed_Harrison. a supplement to oral feeding; it is not suitable for the critically ill. Peripheral PN may be enhanced by small amounts of heparin (1000 U/L) and co-infusion with parenteral fat to reduce osmolarity, but volume constraints still limit the value of this therapy, especially in critical illness.


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InternalMed_Harrison. PICCs may be used to infuse solutions of 20–25% dextrose and 4–7% amino acids, thus avoiding the traumatic complications of percutaneous central vein catheter placement. With PICC lines, however, flow can be position-related, and the lines cannot be exchanged over a wire for infection monitoring. It is important to withdraw blood samples carefully and appropriately from a dual-port PICC because intermixing of the blood sample with even tiny volumes of nutrient infusate will falsely indicate hyperglycemia and hyperkalemia. For all these reasons, centrally placed catheters are preferred in critical illness. The subclavian approach is best tolerated by the patient and is the easiest to dress. The jugular approach is less likely to cause a pneumothorax. Femoral vein catheterization is strongly discouraged because of the risk of catheter infection. For long-term feeding at home, tunneled catheters and implanted ports are used to reduce infection risk and are more acceptable to patients.


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InternalMed_Harrison. discouraged because of the risk of catheter infection. For long-term feeding at home, tunneled catheters and implanted ports are used to reduce infection risk and are more acceptable to patients. Tunneled catheters require placement in the operating room.