Nutrition Support

Dominic Reeds

Nutrient Requirements

GENERAL PRINCIPLES

Energy

Total daily energy expenditure (TEE) is composed of resting energy expenditure (normally ~70% of TEE), the thermic effect of food (normally ~10% of TEE), and energy expenditure of physical activity (normally ~20% of TEE).

Malnutrition and hypocaloric feeding decrease resting energy expenditure to values 15% to 20% below those expected for actual body size, whereas metabolic stressors, such as inflammatory diseases or trauma, often increase energy requirements (usually by <50% of pre-illness values).

It is impossible to determine daily energy requirements precisely with predictive equations because of the complexity of factors that affect metabolic rate. Judicious use of predictive equations can provide a reasonable estimate that should be modified as needed based on the patient's clinical course.

The Harris-Benedict equation provides a reasonable estimate of resting energy expenditure (in kcal/d) in healthy adults. The equation takes into account the effect of body size and lean tissue mass (which is influenced by gender and age) on energy requirements and can be used to estimate total daily energy needs in hospitalized patients:

Men = 66 + (13.7 × W) + (5 × H) - (6.8 × A)

Women = 665 + (9.6 × W) + (1.8 × H) - (4.7 × A)

where W is the weight in kg, H the height in cm, and A is the age in years.

Energy requirements per kilogram of bodyweight are inversely related to body mass index (BMI) (Table 1). The lower range within each category should be considered in insulin-resistant, critically ill patients unless they are depleted in body fat.

Ideal body weight can be estimated based on height. For men, 106 lb is allotted for the first 5 ft, then 6 lb is added for each inch above 5 ft; for women, 100 lb is given for the first 5 ft, with 5 lb added for each additional inch.

Protein

Protein intake of 0.8 g/kg/d meets the requirements of 97% of the adult population.

Protein requirements are affected by several factors, such as the amount of nonprotein calories provided, overall energy requirements, protein quality, and the patient's nutritional status. Protein requirements increase as nonprotein caloric intake declines and patients who are being permissively underfed should receive up to 2 g per kilogram of ideal body weight per day to minimize loss of lean body mass.

Inadequate amounts of any of the essential amino acids result in inefficient utilization.

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Illness increases the efflux of amino acids from skeletal muscle; however, increasing protein intake to >1.2 g/kg/d of prehospitalization body weight in critically ill patients may not reduce the impact of illness on loss of lean body mass (Crit Care Med 1998;26(9):1529).

Table 2 gives approximate protein requirements during different clinical conditions.

Essential fatty acids

The liver can synthesize most fatty acids, but humans lack the desaturase enzyme needed to produce the n-3 and n-6 fatty acid series. Therefore, linoleic acid should constitute at least 2% and linolenic acid at least 0.5% of the daily caloric intake to prevent the occurrence of essential fatty acid deficiency.

The plasma pattern of increased triene-to-tetraene ratio (>0.4) can be used to detect essential fatty acid deficiency.

Patients who are unable to receive intravenous (IV) or oral lipid solutions may receive a daily topical application of 1 tbsp of safflower oil to provide essential fatty acids.

Carbohydrates

Certain tissues, such as bone marrow, erythrocytes, leukocytes, renal medulla, eye tissues, and peripheral nerves, cannot metabolize fatty acids and require glucose (~40 g/d) as a fuel. Other tissues such as the brain prefer glucose (~120 g/d).

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Major minerals

Major minerals are important for ionic equilibrium, water balance, and normal cell function. The following are the daily recommended intakes (enteral and parenteral values, respectively):

Sodium, 0.5 to 5.0 g and 60 to 150 mEq

Potassium, 2 to 5 g and 60 to 100 mEq

Magnesium, 300 to 400 mg and 8 to 24 mEq

Calcium, 800 to 1,200 mg and 5 to 15 mEq

Phosphorus, 800 to 1,200 mg and 12 to 24 mEq

Micronutrients (trace elements and vitamins)

Trace elements and vitamins are essential constituents of enzyme complexes. The recommended dietary intake for trace elements, fat-soluble vitamins, and water-soluble vitamins (Table 3) is set at two standard deviations above the estimated mean so that it will cover the needs of 97% of the healthy population. See Table 3 for specific micronutrient deficiency symptoms.

Table 1 Estimated Energy Requirements for Hospitalized Patients Based on Body Mass Index

BMI (kg/m2)

Energy Requirements (kcal/kg/d)

15

35-40

15-19

30-35

20-24

20-25

25-29

15-20

≥30

<15

Note: These values are recommended for critically ill patients and all obese patients; add 20% of total calories in estimating energy requirements in non-critically ill patients.

Table 2 Recommended Daily Protein Intake

Clinical Condition

Protein Requirements (g/kg IBW/d)a

Normal

0.8

Metabolic “stress” (illness/injury)

1.0-1.5

Acute renal failure (undialyzed)

0.8-1.0

Hemodialysis

1.2-1.4

Peritoneal dialysis

1.3-1.5

IBW, ideal body weight.

a Additional protein intake may be needed to compensate for excess protein loss in specific patient populations such as those with burn injury, open wounds, and protein-losing enteropathy or nephropathy. Lower protein intake may be necessary in patients with chronic renal insufficiency who are not treated by dialysis and certain patients with hepatic encephalopathy.

SPECIAL CONSIDERATIONS

Both the amount and location of prior gut resection influences nutrient needs. Patients with an inadequate length of functional small bowel (<~150 cm) either from resection or medical disease require additional vitamins and minerals if they are not receiving parenteral nutrition. Table 4 provides guidelines for supplementation in these patients.

Distal ileum resection can cause rapid development of B12 deficiency.

Proximal gut resection (stomach or duodenum) can result in iron, calcium, and copper deficiency.

Patients with excessive gastrointestinal (GI) tract losses require additional fluids and electrolytes. An assessment of fluid losses due to diarrhea, ostomy output, and fistula volume should be made to help determine fluid requirements. Knowledge of fluid losses is also useful in calculating intestinal mineral losses by multiplying the volume of fluid loss by an estimate of intestinal fluid electrolyte concentration (Table 5).

Assessment of Nutritional Status

GENERAL PRINCIPLES

Patients should be assessed for protein-energy malnutrition as well as specific nutrient deficiencies.

A thorough history and physical exam combined with appropriate laboratory studies is the best approach to evaluate nutritional status.

DIAGNOSIS

Clinical Presentation

History

Assess for changes in diet pattern (size, number, and content of meals). If present, the reason for altered food intake should be investigated.

Unintentional weight loss of >10% body weight in the last 6 months is associated with a poor clinical outcome (Am J Med 1980;69:491).

Look for evidence of malabsorption (diarrhea, weight loss).

For symptoms of specific nutrient deficiencies, see Table 3.

Consider factors that may increase metabolic stress (infection, inflammatory disease, malignancy, etc.).

Assess patient's functional status (e.g., bedridden, suboptimally active, very active).

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Table 3 Trace Mineral, Fat-Soluble Vitamin, and Water-Soluble Vitamin Requirements and Assessment of Deficiency

Nutrient

Recommended Daily Enteral Intake in Normal Adults

Recommended Daily Parenteral Intake in Normal Adults

Symptoms or Signs of Deficiency

Laboratory Evaluation

Chromium

30-200 mcg

10-20 mcg

Glucose intolerance, peripheral neuropathy, encephalopathy

Serum chromium

Copper

2 mg

0.3 mg

Anemia, neutropenia, osteoporosis, diarrhea

Serum copper, plasma ceruloplasmin

Iodine

150 mcg

70-140 mcg

Hypothyroidism, goiter

Urine iodine, thyroid-stimulating hormone

Iron

10-15 mg

1.0-1.5 mg

Microcytic hypochromic anemia

Serum iron and total iron-binding capacity, serum ferritin

Manganese

1.5 mg

0.2-0.8 mg

Hypercholesterolemia, dementia, dermatitis

Serum manganese

Selenium

50-200 mcg

20-40 mcg

Cardiomyopathy, muscle weakness

Serum selenium, blood glutathione peroxidase activity

Zinc

15 mg

2.5-4.0 mg

Growth retardation, delayed sexual maturation, hypogonadism, alopecia, acro-orificial skin lesion, diarrhea, mental status changes

Plasma zinc

Vitamin K (phylloquinone)

50-100 mcg

100 mcg

Easy bruising/bleeding

Prothrombin time

Vitamin A (retinol)

5,000 International Units

3,300 International Units

Night blindness, Bitot's spots, keratomalacia, follicular hyperkeratosis, xerosis

Serum retinol

Vitamin D (ergocalciferol)

400 International Units

200 International Units

Rickets, osteomalacia, osteoporosis, bone pain, muscle weakness, tetany

Serum 25-hydoxyvitamin D

Vitamin E (α-tocopherol)

10-15 International Units

10 International Units

Hemolysis, retinopathy, neuropathy, abnormal clotting

Serum tocopherol: total lipid (triglyceride and cholesterol) ratio

Vitamin B1 (thiamine)

1.0-1.5 mg

3 mg

Beriberi, cardiac failure, Wernicke's encephalopathy, peripheral neuropathy, fatigue, ophthalmoplegia

RBC transketolase activity

Vitamin B2 (riboflavin)

1.1-1.8 mg

3.6 mg

Cheilosis, sore tongue and mouth, eye irritation, seborrheic dermatitis

RBC glutathione reductase activity

Vitamin B3 (niacin)

12-20 mg

40 mg

Pellagra (dermatitis, diarrhea, dementia), sore mouth and tongue

Urinary N-methylnicotinamide

Vitamin B5 (pantothenic acid)

5-10 mg

10 mg

Fatigue, weakness, paresthesias, tenderness of heels and feet

Urinary pantothenic acid

Vitamin B6 (pyridoxine)

12 mg

4 mg

Seborrheic dermatitis, cheilosis, glossitis, peripheral neuritis, convulsions, hypochromic anemia

Plasma pyridoxal phosphate

Vitamin B7 (biotin)

100-200 mcg

60 mcg

Seborrheic dermatitis, alopecia, mental status change, seizures, myalgia, hyperesthesia

Plasma biotin

Vitamin B9 (folic acid)

400 mcg

400 mcg

Megaloblastic anemia, glossitis, diarrhea

Serum folic acid, RBC folic acid

Vitamin B12 (cobalamin)

5 mcg

5 mcg

Megaloblastic anemia, paresthesias, decreased vibratory or position sense, ataxia, mental status changes, diarrhea

Serum cobalamin, serum methylmalonic acid

Vitamin C (ascorbic acid)

100 mg

100 mg

Scurvy, petechia, purpura, gingival inflammation, and bleeding, weakness, depression

Plasma ascorbic acid, leukocyte ascorbic acid

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Table 4 Guidelines for Vitamin and Mineral Supplementation in Patients with Severe Malabsorption

Supplement

Dose

Route

Prenatal multivitamin with mineralsa

1 tablet daily

PO

Vitamin Da

50,000 units two to three times per week

PO

Calciuma

500 mg elemental calcium tid-qid

PO

Vitamin B12b

1 mg daily

PO

100-500 mcg q1-2 mo

SC

Vitamin Ab

10,000-50,000 units daily

PO

Vitamin Kb

5 mg/d

PO

5-10 mg/wk

SC

Vitamin Eb

30 units/d

PO

Magnesium gluconateb

108-169 mg elemental magnesium qid

PO

Magnesium sulfateb

290 mg elemental magnesium one to three times per week

IM/IV

Zinc gluconate or zinc sulfateb

25 mg elemental zinc daily plus 100 mg elemental zinc per liter intestinal output

PO

Ferrous sulfateb

60 mg elemental iron tid

PO

Iron dextranb

Daily dose based on formula or table

IV

a Recommended routinely for all patients.

b Recommended for patients with documented nutrient deficiency or malabsorption.

Table 5 Electrolyte Concentrations in Gastrointestinal Fluids

Location

Na (mEq/L)

K (mEq/L)

Cl (mEq/L)

HCO3 (mEq/L)

Stomach

65

10

100

—

Bile

150

4

100

35

Pancreas

150

7

80

75

Duodenum

90

15

90

15

Mid-small bowel

140

6

100

20

Terminal ileum

140

8

60

70

Rectum

40

90

15

30

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Physical Examination

Patients can be classified by BMI as underweight (<18.5 kg/m2), normal weight (18.5 to 24.9 kg/m2), overweight (25.0 to 29.9 kg/m2), class I obesity (30.0 to 34.9 kg/m2), class II obesity (35.0 to 39.9 kg/m2), or class III obesity (≥40.0 kg/m2) (Obes Res 1998;6(Suppl 2):S53).

Patients who are extremely underweight (BMI < 14 kg/m2) or those with rapid, severe weight loss (even with supranormal BMI) have a high risk of death and should be considered for admission to the hospital for nutritional support.

Look for tissue depletion (loss of body fat and skeletal muscle wasting).

Assess muscle function (strength testing of individual muscle groups).

Fluid status: Evaluate patients for dehydration (hypotension, tachycardia, mucosal xerosis, etc.) or excess body fluid (edema or ascites).

Evaluate patient for sources of protein or nutrient losses: large wounds, burns, nephrotic syndrome, surgical drains, etc. Quantify the volume of drainage and the concentration of fat and protein content.

Diagnostic Testing

Laboratories

Perform laboratory studies to determine specific nutrient deficiencies only when clinically indicated, as the plasma concentration of many nutrients may not reflect true body stores (Table 3).

Plasma albumin and prealbumin concentration should not be used to assess patients for protein-calorie malnutrition or to monitor the adequacy of nutrition support. While levels of these plasma proteins correlate with clinical outcome, inflammation and injury can alter their synthesis and degradation, consequently limiting their utility in nutritional assessment (Crit Care Med 1982;10:305; Gastroenterology 1990; 99:1845).

Most hospitalized patients are vitamin D deficient and caregivers should have a low threshold for checking plasma 25-OH vitamin D levels (N Engl J Med 1998: 338:777).

Enteral Nutrition

GENERAL PRINCIPLES

Whenever possible, oral/enteral feeding is preferred to parenteral feeding because it limits mucosal atrophy, maintains immunoglobulin A (IgA) secretion, and prevents cholelithiasis. Additionally, oral/enteral feeds are less expensive than parenteral nutrition.

Types of feedings

Hospital diets include a regular diet and those modified in either nutrient content (amount of fiber, fat, protein, or sodium) or consistency (liquid, puréed, soft). There are ways that food intake can often be increased:

Encourage patients to eat.

Provide assistance at mealtime.

Allow some food to be supplied by relatives and friends.

Limit missed meals for medical tests and procedures.

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Avoid unpalatable diets. Milk-based formulas (e.g., Carnation Instant Breakfast) contain milk as a source of protein and fat and tend to be more palatable than other defined formula diets.

Use of calorically dense supplements, for example, Ensure or Boost.

Defined liquid formulas

Polymeric formulas are appropriate for most patients. They contain nitrogen in the form of whole proteins and include blenderized food, milk-based, and lactose-free formulas. Lactose-free formulas (e.g., Osmolite, Ensure) are the most commonly used polymeric formulas in hospitalized patients. These formulas are available as standard iso-osmolar solutions, containing approximately 1 kcal/mL, 16% calories as protein, 55% calories as carbohydrate, and 30% calories as fat. Other formulas are available with modified nutritional content including high-nitrogen, high-calorie, fiber-enriched, and low-potassium/phosphorus/magnesium formulas.

Semielemental (oligomeric) formulas (e.g., Propeptide, Peptamen) contain hydrolyzed protein in the form of small peptides and free amino acids. While these formulas may have benefit in the patients who have exocrine pancreatic insufficiency or short gut, pancreatic enzyme replacement is a less-expensive, equally effective intervention in most of these patients.

Elemental monomeric formulas (e.g., Vivonex, Glutasorb) contain nitrogen in the form of free amino acids and small amounts of fat (<5% of total calories) and are hyperosmolar (550 to 650 mOsm/kg). These formulas are not palatable and require either tube feeding or mixing with other foods or flavorings for oral ingestion. Free amino acids are poorly absorbed, and as a result, absorption of monomeric formulas is not clinically superior to that of oligomeric or polymeric formulas in patients with adequate pancreatic digestive function. These formulas may exacerbate osmotic diarrhea in patients with short gut.

Oral rehydration solutions stimulate sodium and water absorption by taking advantage of the sodium-glucose cotransporter present in the brush border of intestinal epithelium. Oral rehydration therapy can be useful in patients with severe GI fluid and mineral losses, such as those with short bowel syndrome (Clin Ther 1990;12(Suppl A):129). In these patients, it is particularly important that the sodium concentration of the solution be between 90 and 120 mEq/L to avoid intestinal sodium secretion and negative sodium and water balance. The characteristics of several oral rehydration solutions are listed in Table 6.

Tube feeding

Tube feeding is useful in patients who have a functional GI tract but who cannot or will not ingest adequate nutrients.

The type of tube feeding approach selected (nasogastric, nasoduodenal, nasojejunal, gastrostomy, jejunostomy, pharyngostomy, and esophagostomy tubes) depends on physician experience, clinical prognosis, gut patency and motility, risk of aspirating gastric contents, patient preference, and anticipated duration of feeding.

Short-term (<6 weeks) tube feeding can be achieved by placement of a soft, smallbore nasogastric or nasoenteric feeding tube. Tube feeding can be used to supplement oral intake. Although nasogastric feeding is usually the most appropriate route, orogastric feeding in patients with nasal injury or gross nasal deformity and nasoduodenal or nasojejunal feeding in those with gastroparesis can also be used. Nasoduodenal and nasojejunal feeding tubes can be placed at the bedside with a success rate approaching 90% when inserted by experienced personnel (Nutr Clin Pract 2001;16:258).

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Long-term (>6 weeks) tube feeding usually requires a gastrostomy or jejunostomy tube that can be placed endoscopically, radiologically, or surgically, depending on the clinical situation and local expertise.

Percutaneous gastrostomy and jejunostomy can be performed using endoscopic or fluoroscopic techniques.

Surgical gastrostomy and jejunostomy can be performed by open and laparoscopic techniques and are particularly useful when endoscopic and radiologic approaches are technically not possible.

Feeding schedules: Patients who have feeding tubes in the stomach can often tolerate intermittent bolus or gravity feedings, in which the total amount of daily formula is divided into four to six equal portions.

Bolus feedings are given by syringe as rapidly as tolerated.

Gravity feedings are infused over 30 to 60 minutes.

The patient's upper body should be elevated by 30 to 45 degrees during feeding and for at least 2 hours afterwards. Tubes should be flushed with water after each feeding. Intermittent feedings are useful for patients who cannot be positioned with continuous head-of-the-bed elevation or who require greater freedom from feeding. Patients who experience nausea and early satiety with bolus gravity feedings may require continuous infusion at a slower rate.

Continuous feeding can often be started at 20 to 30 mL/hr and advanced by 10 mL/hr every 6 hours until the feeding goal is reached. Patients who have gastroparesis often tolerate gastric tube feedings when they are started at a slow rate (e.g., 10 mL/hr) and advanced by small increments (e.g., 10 mL/hr every 8 to 12 hours). Patients with severe gastroparesis may require passage of the feeding tube tip past the ligament of Treitz. Continuous feeding should always be used when feeding directly into the duodenum or jejunum to avoid distention, abdominal pain, and dumping syndrome.

Jejunal feeding may be possible in closely monitored patients with mild to moderate acute pancreatitis (J Am Coll Nutrition 1995;14(6):662).

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Contraindications: The intestinal tract cannot be used effectively in some patients due to:

Persistent nausea or vomiting

Intolerable postprandial abdominal pain or diarrhea

Mechanical obstruction or severe hypomotility

Severe malabsorption

Presence of high-output fistulas

Table 6 Characteristics of Selected Oral Rehydration Solutions

Product

Na (mEq/L)

K (mEq/L)

Cl (mEq/L)

Citrate (mEq/L)

kcal/L

CHO (g/L) mOsm

Equalyte

78

22

68

30

100

25

305

CeraLyte 70

70

20

98

30

165

40

235

CeraLyte 90

90

20

98

30

165

40

260

Pedialyte

45

20

35

30

100

20

300

Rehydralyte

74

19

64

30

100

25

305

Gatorade

20

3

NA

NA

210

45

330

WHOa

90

20

80

30

80

20

200

WashingtonUniversityb

105

0

100

10

85

20

250

Note: Mix formulas with sugar-free flavorings as needed for palatability.

NA, not applicable; WHO, World Health Organization.

a WHO formula: Mix ¾ tsp sodium chloride, ½ tsp sodium citrate, ¼ tsp potassium chloride, and 4 tsp glucose (dextrose) in 1 L (4¼ cups) distilled water.

b Washington University formula: Mix ¾ tsp sodium chloride, ½ tsp sodium citrate, and 3 tbsp + 1 tsp Polycose powder in 1 L (4¼ cups) distilled water.

COMPLICATIONS

Mechanical complications

Nasogastric feeding tube misplacement occurs more commonly in unconscious patients. Intubation of the tracheobronchial tree has been reported in up to 15% of patients. Intracranial placement can occur in patients with skull fractures.

Erosive tissue damage can lead to nasopharyngeal erosions, pharyngitis, sinusitis, otitis media, pneumothorax, and GI tract perforation.

Tube occlusion is often caused by inspissated feedings or pulverized medications given through small-diameter (<No. 10 French) tubes. Frequent flushing of the tube with 30 to 60 mL of water and avoiding administration of pill fragments or “thick” medications help to prevent occlusion. Techniques used to unclog tubes include the use of a small-volume syringe (10 mL) to flush warm water or pancreatic enzymes (Viokase dissolved in water) through the tube.

Hyperglycemia

Achieving tight control of blood glucose (<110 mg/dL) in critically ill patients may improve outcomes; however, it increases the risk of hypoglycemia (N Engl J Med 2001;345:1359).

Subcutaneously administered insulin can usually maintain good glycemic control. IV insulin drip protocols may be used to control blood glucose in critically ill patients with anasarca or hemodynamic instability to ensure adequate insulin absorption.

Intermediate-duration insulin (e.g., NPH) can often be used safely once tube feedings reach 1,000 kcal/d. Long-duration insulin (e.g., detemir, glargine) should be used with caution in critically ill patients because changes in clinical status may affect pharmacokinetics and increase the risk of sustained hypoglycemia.

Patients who are receiving bolus feeds should receive short-acting insulin at the time of the feed.

Patients who are being given continuous (24 hours a day) feeding should receive intermediate- or long-duration insulin every 12 to 24 hours when clinically stable.

Pulmonary aspiration

The etiology of pulmonary aspiration can be difficult to determine in tube-fed patients because aspiration can occur from refluxed tube feedings or oropharyngeal secretions that are unrelated to feedings.

Addition of food coloring to tube feeds should not be used for the diagnosis of aspiration. This method is insensitive for diagnosis, and several case reports suggest that food coloring can be absorbed by the GI tract in critically ill patients, which can lead to serious complications and death (N Engl J Med 2000;343:1047).

Gastric residuals are poorly predictive of aspiration risk.

Prevention of reflux: Decrease gastric acid secretion with pharmacologic therapy (H2 blocker, PPI), elevate head of bed during feeds, and avoid gastric feeding in

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high-risk patients (e.g., those with gastroparesis, frequent vomiting, gastric outlet obstruction).

GI complications

Nausea, vomiting, and abdominal pain are common.

Diarrhea is often associated with antibiotic therapy (JPEN 1991;15:27) and the use of liquid medications that contain nonabsorbable carbohydrates, such as sorbitol (Am J Med 1990;88:91). If diarrhea from tube feeding persists after proper evaluation of possible causes, a trial of antidiarrheal agents or fiber is justified. Diarrhea is common in patients who receive tube feeding and occurs in up to 50% of critically ill patients.

Diarrhea in patients with short gut, who do not have other causes such as Clostridium difficile infection, may be minimized by use of small, frequent meals that do not contain concentrated sweets (e.g., soda). Intestinal transit time should be maximized to allow nutrient absorption using tincture of opium, loperamide, or diphenoxylate. Low-dose clonidine (0.025 to 0.05 mg orally twice a day) may be used to reduce diarrhea in hemodynamically stable patients with short bowel syndrome (JPEN 2004;28(4):265).

Intestinal ischemia/necrosis has been reported in patients receiving tube feeding. These cases have occurred predominantly in critically ill patients receiving vasopressors for blood pressure support in conjunction with enteral feeding. There are no reliable clinical signs for diagnosis, and the mortality rate is high. Caution should be used when enterally feeding critically ill patients requiring pressors.

Parenteral Nutrition

GENERAL PRINCIPLES

Patients who are unable to consume “adequate” nutrients for a “prolonged” period of time by oral or enteral routes require parenteral nutritional therapy to prevent the adverse effects of malnutrition.

The decision to use parenteral nutrition can be difficult because the precise definition of “adequate” and “prolonged” is not clear and depends on the patient's body fat, lean tissue mass, preexisting medical illnesses, and level of metabolic stress.

In general, parenteral nutrition should be considered if energy intake has been or is anticipated to be inadequate (<50% of daily requirements) for more than 7 to 10 days and enteral feeding is not feasible. The efficacy of this approach has not been tested in clinical trials.

Routine use of immediate postoperative total parenteral nutrition (TPN) does not appear to improve outcomes in unselected patients (Ann Surg 1993;217(2):185).

Recommendations

Central parenteral nutrition (CPN)

The infusion of hyperosmolar (usually >1,500 mOsm/L) nutrient solutions requires a large-bore, high-flow vessel to minimize vessel irritation and damage.

Percutaneous subclavian vein catheterization with advancement of the catheter tip to the junction of the superior vena cava and right atrium is the most commonly used technique for CPN access. The internal jugular, saphenous, and femoral veins are also used, although less desirable due to decreased patient

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comfort and difficulty in maintaining sterility. Catheters that are tunneled under the skin prior to entering the vascular tree are preferred in patients who are likely to receive >8 weeks of TPN to reduce the risk of mechanical failure.

Peripherally inserted central venous catheters (which reduce the risk of pneumothorax) are increasingly used to provide CPN in patients with adequate antecubital vein access. These catheters are not suitable for patients in whom CPN is anticipated to be necessary for an extended duration (>6 months).

CPN macronutrient solutions

Crystalline amino acid solutions containing 40% to 50% essential and 50% to 60% nonessential amino acids (usually with little or no glutamine, glutamate, aspartate, asparagine, tyrosine, and cysteine) are used to provide protein needs (Table 2). Infused amino acids are oxidized and should be included in the estimate of energy provided as part of the parenteral formulation.

Some amino acid solutions have been modified for specific disease states such as those enriched in branched-chain amino acids for use in patients who have hepatic encephalopathy and solutions that contain mostly essential amino acids for use in patients with renal insufficiency.

Glucose (dextrose) in IV solutions is hydrated; each gram of dextrose monohydrate provides 3.4 kcal. While there is no absolute requirement for glucose in most patients, providing >150 g glucose per day maximizes protein balance.

Lipid emulsions are available as a 10% (1.1 kcal/mL) or 20% (2.0 kcal/mL) solution and provide energy as well as a source of essential fatty acids. Emulsion particles are similar in size and structure to chylomicrons and are metabolized like nascent chylomicrons after acquiring apoproteins from contact with circulating endogenous high-density lipoprotein particles. Lipid emulsions are as effective as glucose in conserving body nitrogen economy once absolute tissue requirements for glucose are met. The optimal percentage of calories that should be infused as fat is not known, but 20% to 30% of total calories is reasonable for most patients. The rate of infusion should not exceed 1.0 kcal/kg/hr (0.11 g/kg/hr) because most complications associated with lipid infusions have been reported when providing more than this amount (Curr Opin Gastroenterol 1991;7:306). A rate of 0.03 to 0.05 g/kg/hr is adequate for most patients who are receiving continuous CPN. Lipid emulsions should not be given to patients who have triglyceride concentrations of >400 mg/dL. Moreover, patients at risk for hypertriglyceridemia should have serum triglyceride concentrations checked at least once during lipid emulsion infusion to ensure adequate clearance. Underfeeding obese patients by the amount of lipid calories that would normally be given (e.g., 20% to 30% of calories) facilitates mobilization of endogenous fat stores for fuel and may improve insulin sensitivity. IV lipids should still be administered twice per week to these patients to provide essential fatty acids.

COMPLICATIONS

Mechanical complications

Complications at time of line placement include pneumothorax, air embolism, arterial puncture, hemothorax, and brachial plexus injury.

Thrombosis and pulmonary embolus: Radiologically evident subclavian vein thrombosis occurs commonly; however, clinical manifestations (upper extremity

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edema, superior vena cava syndrome) are rare. Fatal microvascular pulmonary emboli can be caused by nonvisible precipitate in parenteral nutrition solutions. Inline filters should be used with all solutions to minimize the risk of these emboli.

Metabolic complications: Usually caused by overzealous or inadequate nutrient administration:

Fluid overload

Hypertriglyceridemia

Hypercalcemia

Specific nutrient deficiencies. Consider providing supplemental thiamine (100 mg for 3 to 5 days) during initiation of CPN in patients with risk for thiamine deficiency (e.g., alcoholism).

Hypoglycemia

Hyperglycemia should be avoided because it is associated with an increased risk of infection. Blood glucose goals for closely monitored intensive care unit (ICU) patients are ideally 80 to 120 mg/dL. Management of patients with hyperglycemia or type 2 diabetes (Mayo Clin Proc 1996;71:587) can be performed in the following way:

If blood glucose is >200 mg/dL, consider obtaining better control of blood glucose before starting CPN.

If CPN is started, (a) limit dextrose to <200 g/d, (b) add 0.1 units of regular insulin for each gram of dextrose in CPN solution (e.g., 15 units for 150 g), (c) discontinue other sources of IV dextrose, and (d) order routine, regular insulin with blood glucose monitoring by fingerstick every 4 to 6 hours or IV regular insulin infusion with blood glucose monitoring by fingerstick every 1 to 2 hours.

In outpatients who use insulin, an estimate of the reduction in blood sugar that will be caused by the administration of 1 unit of insulin may be calculated by dividing 1,500 by the total daily insulin dose (e.g., for a patient receiving 50 units of insulin as an outpatient, 1 unit of insulin may be predicted to reduce plasma glucose concentration by 1,500/50 = 30 mg/dL).

If blood glucose remains >200 mg/dL and the patient has been requiring SC insulin, add 50% of the supplemental short-acting insulin given in the last 24 hours to the next day's CPN solution and double the amount of SC insulin sliding-scale dose for blood glucose values >200 mg/dL.

The insulin-to-dextrose ratio in the CPN formulation should be maintained while the CPN dextrose content is changed.

Infectious complications

Catheter-related sepsis is the most common life-threatening complication in patients who receive CPN and is most commonly caused by skin flora: Staphylococcus epidermidis and Staphylococcus aureus.

In immunocompromised patients and those with long-term (>2 weeks) CPN, Enterococcus, Candida species, Escherichia coli, Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Proteus, and Xanthomonas should be considered.

The principles of evaluation and management of suspected catheter-related infection are outlined in the Infectious Disease section.

Although antibiotics are often infused through the central line, the antibiotic lock technique has been used successfully to treat and prevent central catheter-related infections (Nutrition 1998;14:466; Antimicrob Agents Chemother

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1999;43:2200). This technique involves local delivery of antibiotics in the catheter without systemic administration.

Hepatobiliary complications. Although these abnormalities are usually benign and transient, more serious and progressive disease may develop in a small subset of patients, usually after 16 weeks of CPN therapy or in those with short bowel (Diseases of the Liver. 7th ed. Philadelphia: JB Lippincott, 1993:1505).

Biochemical: Elevated aminotransferases and alkaline phosphatase are commonly seen.

Histologic alterations: Steatosis, steatohepatitis, lipidosis, phospholipidosis, cholestasis, fibrosis, and cirrhosis have all been seen.

Biliary complications usually occur in patients who receive CPN for >3 weeks.

Acalculous cholecystitis

Gallbladder sludge

Cholelithiasis

Routine efforts to prevent hepatobiliary complications in all patients receiving long-term CPN include providing a portion (20% to 40%) of calories as fat, cycling CPN so that the glucose infusion is stopped for at least 8 to 10 hours per day, encouraging enteral intake to stimulate gallbladder contraction and maintain mucosal integrity, avoiding excessive calories, and preventing hyperglycemia.

If abnormal liver biochemistries or other evidence of liver damage occurs, evaluation for other possible causes of liver disease should be performed.

If mild hepatobiliary complications are noted parenteral nutrition does not need to be discontinued, but the same principles used in preventing hepatic complications can be applied therapeutically.

When cholestasis is present, copper and manganese should be deleted from the CPN formula to prevent accumulation in the liver and basal ganglia. A 4-week trial of metronidazole or ursodeoxycholic acid has been reported to be helpful in some patients.

Metabolic bone disease

Metabolic bone disease has been observed in patients receiving long-term (>3 months) CPN.

Patients may be asymptomatic. Clinical manifestations include bone fractures and pain (Annu Rev Nutr 1991;11:93). Demineralization may be seen in radiologic studies. Osteopenia, osteomalacia, or both may be present.

The precise causes of metabolic bone disease are not known, but several mechanisms have been proposed, including aluminum toxicity, vitamin D toxicity, and negative calcium balance.

Several therapeutic options should be considered in patients who have evidence of bone abnormalities.

Remove vitamin D from the CPN formulation if the parathyroid hormone and 1,25-hydroxy vitamin D levels are low.

Reduce protein to <1.5 g/kg/d because amino acids cause hypercalciuria.

Maintain normal magnesium status because magnesium is necessary for normal parathormone action and renal conservation of calcium.

Provide oral calcium supplements of 1 to 2 g/d.

Consider bisphosphonate therapy to decrease bone resorption.

Peripheral parenteral nutrition

Peripheral parenteral nutrition is often considered to have limited usefulness because of the high risk of thrombophlebitis.

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Appropriate adjustments in the management of peripheral parenteral nutrition can increase the life of a single infusion site to >10 days. The following guidelines are recommended:

Provide at least 50% of total energy as a lipid emulsion piggybacked with the dextrose-amino acid solution.

Add 500 to 1,000 U heparin and 5 mg hydrocortisone per liter (to decrease phlebitis).

Place a fine-bore 22- or 23-gauge polyvinylpyrrolidone-coated polyurethane catheter in as large a vein as possible in the proximal forearm using sterile technique.

Place a 5-mg glycerol trinitrate ointment patch (or 1/4 in. of 2% nitroglycerin ointment) over the infusion site.

Infuse the solution with a volumetric pump.

Keep the total infused volume <3,500 mL/d.

Filter the solution with an inline 1.2-m filter (Nutrition 1994;10:49).

Long-term home parenteral nutrition

Long-term home parenteral nutrition is usually given through a tunneled catheter or an implantable subcutaneous port inserted in the subclavian vein.

Nutrient formulations can be infused overnight to permit daytime activities in patients who are able to tolerate the fluid load. IV lipids may not be necessary in patients who are able to ingest and absorb adequate amounts of fat.

Monitoring nutrition support

Adjustment of the nutrient formulation is often needed as medical therapy or clinical status changes.

When nutrition support is initiated, other sources of glucose (e.g., peripheral IV dextrose infusions) should be stopped and the volume of other IV fluids adjusted to account for CPN.

Vital signs should be checked every 8 hours.

In certain patients, body weight, fluid intake, and fluid output should be followed daily.

Serum electrolytes (including phosphorus) should be measured every 1 or 2 days after CPN is started until values are stable and then rechecked weekly.

Serum glucose should be checked up to every 4 to 6 hours by fingerstick until blood glucose concentrations are stable and then rechecked weekly.

If lipid emulsions are being given, serum triglycerides should be measured during lipid infusion in patients at risk for hypertriglyceridemia to demonstrate adequate clearance (triglyceride concentrations should be <400 mg/dL).

Careful attention to the catheter and catheter site can help to prevent catheter-related infections.

Gauze dressings should be changed every 48 to 72 hours or when contaminated or wet, but transparent dressings can be changed weekly.

Tubing that connects the parenteral solutions with the catheter should be changed every 24 hours.

A 0.22-µm filter should be inserted between the IV tubing and the catheter when lipid-free CPN is infused and should be changed with the tubing.

A 1.2-µm filter should be used when a total nutrient admixture containing a lipid emulsion is infused.

When a single-lumen catheter is used to deliver CPN, the catheter should not be used to infuse other solutions or medications (with the exception of compatible antibiotics) and it should not be used to monitor central venous pressure.

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When a triple-lumen catheter is used, the distal port should be reserved solely for the administration of CPN.

Refeeding the Severely Malnourished Patient

COMPLICATIONS

Initiating nutritional therapy in patients who are severely malnourished and have had minimal nutrient intake can have adverse clinical consequences and precipitate the refeeding syndrome.

Hypophosphatemia, hypokalemia, and hypomagnesemia: Rapid and marked decreases in these electrolytes occur during initial refeeding because of insulinstimulated increases in cellular mineral uptake from extracellular fluid. For example, plasma phosphorus concentration can fall below 1 mg/dL and cause death within hours of initiating nutritional therapy if adequate phosphate is not given (Am J Clin Nutr 1981;34:393).

Fluid overload and congestive heart failure are associated with decreased cardiac function and insulin-induced increased sodium and water reabsorption in conjunction with nutritional therapy containing water, glucose, and sodium. Renal mass may be reduced, limiting the ability to excrete salt or water loads.

Cardiac arrhythmias: Patients who are severely malnourished often have bradycardia. Sudden death from ventricular tachyarrhythmias can occur during the first week of refeeding in severely malnourished patients and may be associated with a prolonged QT interval (Ann Intern Med 1985;102:49) or plasma electrolyte abnormalities. Patients with EKG changes should be monitored on telemetry, possibly in an ICU.

Glucose intolerance: Starvation causes insulin resistance such that refeeding with high-carbohydrate meals or large amounts of parenteral glucose can cause marked elevations in blood glucose concentration, glucosuria, dehydration, and hyperosmolar coma. In addition, carbohydrate refeeding in patients who are depleted in thiamine can precipitate Wernicke's encephalopathy.

Recommendations

Careful evaluation of cardiovascular function and plasma electrolytes (history, physical examination, electrocardiogram, and blood tests) and correction of abnormal plasma electrolytes are important before initiation of feeding.

Refeeding by the oral or enteral route involves the frequent or continuous administration of small amounts of food or an isotonic liquid formula.

Parenteral supplementation or complete parenteral nutrition may be necessary if the intestine cannot tolerate feeding.

During initial refeeding, fluid intake should be limited to approximately 800 mL/d plus insensible losses. Adjustments in fluid and sodium intake are needed in patients who have evidence of fluid overload or dehydration.

Changes in body weight provide a useful guide for evaluating the efficacy of fluid administration. Weight gain greater than 0.25 kg/d or 1.5 kg/wk probably represents fluid accumulation in excess of tissue repletion. Initially approximately 15 kcal/kg, containing approximately 100 g carbohydrate and 1.5 g protein per kilogram of actual body weight, should be given daily.

The rate at which the caloric intake can be increased depends on the severity of the malnutrition and the tolerance to feeding. In general, increases of 2 to 4 kcal/kg every 24 to 48 hours are appropriate.

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Sodium should be restricted to approximately 60 mEq or 1.5 g/d, but liberal amounts of phosphorus, potassium, and magnesium should be given to patients who have normal renal function.

All other nutrients should be given in amounts needed to meet the recommended dietary intake (Table 3).

Bodyweight, fluid intake, urine output, plasma glucose, and electrolyte values should be monitored daily during early refeeding (first 3 to 7 days) so that nutritional therapy can be appropriately modified when necessary.