Parenteral Nutrition Indications In circumstances in which lack of function of the GI tract prevents oral or enteral nutrition, parenteral nutrition (PN) is used. PN is expensive, however, and carries a high risk of complications. IV nutrition therefore is reserved for situations in which no there are no other options for providing nutritional support. Examples of situations in which PN is indicated appear in Table 12 2. Although well-nourished patients with GI dysfunction can receive conventional IV fluids for 7 10 d without harmful effects, patients with existing nutritional deficits or metabolic stress and those not expected to resume oral intake for 5 10 d need PN within 3 5 d. The decision to initiate PN is not an emergency. Adverse effects of PN are less likely to occur in patients who have good glycemic control, stable hemodynamic status, and electrolyte levels within normal limits. Issues such as prognosis, possibility of benefit, and the patient's views regarding artificial feeding also are factors in the decision to begin PN. Table 12 2 Indications for Parenteral Nutrition
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| | Category | Example |
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| Conditions that impair absorption of nutrients | Short-bowel syndrome | | Enterocutaneous fistula | | Infectious colitis | | Radiation or chemotherapy effects | | Small-bowel obstruction | | Need for bowel rest | Inflammatory bowel disease | | Ischemic bowel | | Severe pancreatitis | | Chylous fistula | | Preoperative status | | Motility disorders | Prolonged ileus, scleroderma, pseudoobstruction, visceral organ myopathy | | Inability to achieve or maintain enteral access | Unstable clinical condition | | Hyperemesis gravidarum | | Eating disorders |
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Composition of PN Formulas PN formulas are highly complex IV fluids containing the nutrients essential for metabolism and growth: protein, carbohydrates, lipids, electrolytes, vitamins, trace elements, and water. The composition of PN formulas can be tailored to meet the demands of hypermetabolic illness and to accommodate limitations in organ function. Depending on hospital policy, PN formulas can be compounded in two ways. All of the ingredients can be mixed in a single container, a method called total nutrient admixture (TNA), or the lipid emulsion can be excluded from the primary solution and administered separately. (Lipid emulsions are isotonic and can be given safely by peripheral vein.) Although TNA offers many advantages over conventional dextrose/amino acid formulas, numerous factors affect the stability of the formula. The integrity of the PN formula is a critical consideration that demands the expertise of a pharmacist familiar with stability and compatibility data. Protein: Supplied as crystalline amino acids in a mix of essential and nonessential amino acids. Standard amino acid solutions are available in concentrations ranging from 3% to 15%, the upper range being used most frequently in adults. In general, 1 g of amino acids is equivalent to 1 g of protein. As with dietary protein, IV amino acids yield 4 kcal/g. Manufacturers offer modified amino acids to meet disease- and age-specific requirements. For example, specialty formulas for renal failure contain increased amounts of essential amino acids or provide only essential amino acids. Hepatic failure amino acid mixtures contain higher amounts of branched-chain amino acids and decreased aromatic amino acids. Higher costs and conflicting scientific evidence on effectiveness limit the routine use of specialty amino acid mixtures. Carbohydrate: Dextrose monohydrate is the principal energy substrate in PN formulas. This form of carbohydrate provides 3.4 kcal in concentrations ranging from 3% to 70%. Studies have shown that dextrose dosages between 4 7 mg/kg/min provide optimal protein sparing, although hyperglycemia occurs less often when the dextrose infusion is limited to 4 mg/kg/min. Fat: IV fat emulsions contain soybean oil or a mixture of safflower and soybean oils with egg phospholipid added as an emulsifier. Patients allergic to eggs or soybeans may have reactions to lipid emulsions, including hives, back pain, shortness of breath, and anaphylactic shock. Lipid emulsions are available in concentrations of 10%, 20%, and 30% providing 1.1, 2.0, and 3.0 kcal/mL, respectively. More efficient lipid clearance occurs with 20% fat emulsions than with 10% products, making the 20% form preferable, especially for pediatric patients. Provision of 1 4% of the patient's daily energy requirements as lipid emulsion prevents essential fatty acid deficiency, a condition that causes dry skin, hair loss, poor wound healing, and diarrhea after weeks to months of fat-free parenteral feedings. However, in current practice patients typically receive up to 50% of parenteral calories as fat. Current guidelines for adults set the daily limit for lipid dose at 2.5 g/kg, but a growing body of evidence suggests that 1 g/kg may be a safer limit. The ability to furnish a more balanced fuel mix decreases the adverse effects associated with infusing large amounts of dextrose. However, patients with a triglyceride level  400 mg/dL should not receive lipid emulsions. Monitor triglyceride level to determine whether lipid emulsion can safely be introduced at a later time. On the other hand, a history of type IV hypertriglyceridemia is an absolute contraindication to use of IV fat emulsions. Electrolytes: PN formulas must contain sufficient electrolytes for critical metabolic activities. The usual electrolyte profile of PN formulas is sodium, potassium, calcium, magnesium, chloride, acetate, and phosphorus. Unlike conventional IV fluids, electrolyte PN formulas contain the acetate or chloride salt of the electrolyte to help maintain acid base balance. Sodium bicarbonate is used in PN but may precipitate additives, particularly calcium and magnesium. In most cases, hospital pharmacies offer a standard electrolyte product that provides typical maintenance doses of electrolytes. Table 12 3 lists daily electrolyte requirements for adult patients in stable condition. Patients with diarrhea, fistula output, and gastric losses often have altered electrolyte homeostasis and need higher levels of certain electrolytes. On the other hand, the electrolyte content of the PN formula may have to be restricted if a patient has impaired renal function. Table 12 3 Electrolytes for Parenteral Nutrition
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| | Electrolyte | Form | Recommended Daily Requirement |
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| Sodium | Sodium chloride | 1 2 mEq/kg | | Sodium acetate | | Sodium phosphate | | Potassium | Potassium chloride | 1 2 mEq/kg | | Potassium acetate | | Potassium phosphate | | Chloride | Sodium chloride | As needed for acid base balance | | Potassium chloride | | Acetate | Sodium acetate | As needed for acid base balance | | Potassium acetate | | Phosphate | Sodium phosphate | 20 40 mmol | | Potassium phosphate | | Magnesium | Magnesium sulfate | 8 20 mEq | | Calcium | Calcium gluconate | 10 15 mEq |
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Vitamins: All PN formulas must contain the vitamins needed to support normal metabolism. Life-threatening vitamin deficiencies can develop within 2 3 wk in patients who receive PN without vitamins. Table 12 4 lists the composition of a typical parenteral vitamin product for adults. Individual vitamin products, such as A, C, and folic acid, are used to supplement the standard multivitamin combination when a disease-specific or treatment-related deficiency exists. Table 12 4 Parenteral Vitamin Formulas
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| | Vitamin | Dose/10 mL |
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| A (retinol) | 1 mg (3300 IU) | B1 (thiamin)
| 6 mg | B2 (riboflavin)
| 3.6 mg | B3 (niacin)
| 40 mg | B6 (pyridoxine)
| 6 mg | B12 (cobalamin)
| 5 mcg | | Biotin | 60 mcg | | C (ascorbic acid) | 200 mg | | D (ergocalciferol) | 5 mcg (200 IU) | | E (tocopherol) | 10 IU | | Folic acid | 600 mcg | | K | 150 mcg |
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Trace Minerals: Trace minerals are essential for efficient substrate utilization and other supportive functions. Typical PN solutions contain zinc, chromium, copper, and manganese according to established guidelines. Table 12 5 shows dosing recommendations for trace minerals. Patients receiving long-term PN also need selenium to prevent potentially fatal cardiomyopathy. Commercial trace mineral products do not contain iron. In the past, iron was frequently added to PN formulas in the form of iron dextran, but this practice has fallen out of favor because of concerns about the potential for adverse reactions to IV iron. Current guidelines call for administering iron as a separate infusion as needed. Clinical conditions that impair trace mineral excretion may necessitate restricting certain trace minerals in PN formulas. For example, in patients with biliary disease copper and manganese must be restricted from PN formulas to avoid toxicity. Table 12 5 Trace Element Requirements for Parenteral Nutrition
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| | Element | Recommended Daily Dose |
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| Zinc | 2.5 5.0 mga
| | Copper | 0.3 0.5 mg | | Selenium | 20 60 mcg | | Chromium | 10 15 mcg | | Manganese | 60 100 mcg |
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aRequirements may be as high as 15 mg/d in stress states or in patients with high-output fistulas. |
Central versus Peripheral Administration PN formulas that rely on glucose as a primary energy source frequently have an osmolarity that approaches 1800 mOsm/L, more than twice the limit for administration through peripheral veins. Safe infusion of such hypertonic fluids requires placement of an IV line in the central venous circulation, as described in Chapter 13. However, the osmolarity of PN formulas that contain lipid emulsion and low concentrations of dextrose may fall below 900 mOsm/L, making these formulas suitable for peripheral administration. Peripheral parenteral nutrition (PPN) is appropriate for patients with adequate peripheral venous access who need PN for a brief time, usually less than 2 wk. Because peripheral PN formulas contain relatively low concentrations of nutrients, this form of nutritional support is more helpful in preventing malnutrition than in correcting existing deficits. For similar reasons, patients with elevated requirements due to hypermetabolism or those who need fluid restriction are not candidates for PPN. Initiating and Managing Parenteral Nutrition Beginning Parenteral Nutrition: Because PN can induce metabolic disturbances or worsen existing problems, do not start PN until a patient has a stable fluid and electrolyte profile. It is usually unwise to begin PN in a patient who needs large amounts of fluid, may need resuscitation after trauma, or who is in a septic state. Recommended baseline laboratory tests are serum electrolytes (including ionized calcium, magnesium, and phosphorus), glucose, prealbumin, triglycerides, creatinine, BUN, and liver function tests. These measurements help identify whether the patient is at risk of metabolic complications and help guide the design of the initial PN formula. Begin PN at a reduced level and advance to goal according to the patient's response. Because carbohydrate is the substrate most likely to induce metabolic disturbances, initial formulas frequently have a limited dextrose load, usually 200 250 g for the first day. Many institutional protocols allow patients to receive the target level of protein and lipid emulsion initially and increase dextrose to goal over 2 d. Some situations call for a more cautious introduction of PN. A patient with a baseline serum glucose level of 120 150 mg/dL, for example, should receive only 100 150 g of dextrose in an initial PN formula. Increase the dextrose in the PN formula over several days while closely observing serum glucose level and insulin requirements. Refeeding Syndrome: Beginning PN at a reduced level is prudent for patients at risk of refeeding syndrome, a life-threatening metabolic complication that occurs in the setting of severe weight loss or long-standing malnutrition. Risk factors for this problem include anorexia nervosa, chronic alcoholism, cancer cachexia, and other wasting syndromes. In refeeding syndrome, severe fluid and electrolyte disturbances occur in the first few days of therapy. The hallmark of refeeding syndrome is hypophosphatemia, which can be fatal if not recognized and corrected promptly. To avoid refeeding syndrome for patients at risk, current guidelines call for correcting phosphate levels  2.0 mEq/dL before beginning PN. In this setting, the initial PN formula should limit dextrose to 150 g and begin with only 50% of the patient's caloric requirements. Vigilant electrolyte replacement is essential and may take several days to achieve full repletion. Calorie and protein intake should progress to goal only when fluid and electrolyte status stabilizes. Ordering PN: Writing orders for PN is a step-by-step process that takes into account energy needs, nutrient requirements, and electrolyte status. The first step is to set goals for energy intake and to distribute the calories among the protein, carbohydrate, and fat in the PN formula. The following example illustrates these steps for a 70-kg man. The formula produced in this process is a reasonable estimated goal. This PN can then be adjusted to account for clinical circumstances that affect nutrient needs, such as severity of illness and organ function. | | 1. Establish goals for energy and protein intake. | | a. Provide 25 30 kcal/kg. For a 70-kg man, the range is 1750 2100 kcal/d. (See Chapter 11 regarding use of adjusted body weight.) Start at the low end of the range to avoid overfeeding. b. Give protein 1.0 1.5 g/kg, a range of 70 105 g/d for a 70-kg man. Round the goal to 100 g to meet the patient's needs and to simplify compounding. |
2. Determine nonprotein calories. Subtract protein calories from total calories (100 x 4 kcal/g = 400 protein calories). Example: 1750 400 = 1350 nonprotein calories. 3. Determine carbohydrate dose. The standard lipid dose for most adult patients is 50 g or 500 kcal. Subtract lipid calories from nonprotein calories to determine the amount of dextrose needed to meet the patient's energy needs. Example: 1350 500 = 850 carbohydrate calories. Divide the calorie goal for carbohydrate by 3.4 cal/g. Example: 850 3.4 = 250 g. 4. Order the PN formula. Total energy, 1750 kcal; protein, 100 g; carbohydrate, 250 g; fat, 50 g. Safety guidelines for PN call for ordering substrates in grams to avoid confusion. (Some hospitals require that these values be converted to percent solutions in the PN order.) Consult with a pharmacist. As Table 12 6 shows, the identical PN formula can be adjusted to meet the patient's hydration requirements by use of different concentrations of amino acids, dextrose, and fat. 5. Make appropriate additions to PN formula. Individualize the electrolyte content of the PN formula according to the patient's laboratory tests and organ function. Sodium and potassium are available as both chloride and acetate salts. Using higher or lower amounts of these salts can help maintain acid base balance. Stability and compatibility limits exist for calcium, phosphorus, and magnesium. Many hospitals use standard formulations for vitamins and trace minerals to avoid the need to order each entity individually. |
Table 12 6 Adjusting the Volume of Parenteral Nutrition Formulasa
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| | Example Formula | Standard PN | Fluid Restriction | High Volume |
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| Goal: 1750 kcal | | | | | Protein: 100 g | 10% AA 1000 mL | 15% AA 500 mL | 10% AA 1000 mL | | Dextrose: 250 g | D50W 500 mL
| D70W 357 mL
| D25W 1000 mL
| | Lipid: 50 g | 20% fat 250 mL | 30% fat 204 mL | 10% fat 500 mL | | Volume | 1750 mL | 1265 mL | 2500 mL |
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aHighly concentrated or dilute formulas may affect stability of total nutrient admixture. AA = amino acids. |
Monitoring Response to Therapy Carefully monitor patients receiving PN to identify problems and to assess progress toward the therapeutic goal. Measure electrolytes, including calcium, magnesium, and phosphorus, daily until the levels are stable, and order weekly liver function tests and prealbumin and triglyceride levels. Measure blood glucose level by fingerstick every 6 h until the level is stable. Patients receiving insulin or tapering doses of steroids and those with changing clinical status may need closer blood glucose monitoring. Typical PN protocols call for weighing the patient daily and keeping accurate and intake and output records. No single criterion is a reliable indicator of the effectiveness of PN. Because indicators of protein status are affected by illness, albumin and prealbumin levels are not reliable markers of response to therapy. Nitrogen balance studies do shed light on the adequacy of protein intake, particularly when serial studies are performed. Finally, clinical status is evidence that the a nutritional regimen is appropriate. Adequate wound healing, increased stamina, and improved functional status all suggest the nutritional regimen is meeting the patient's needs. Preventing and Managing Complications Hyperglycemia: The most common metabolic complication of PN. Severe hyperglycemia causes osmotic diuresis that depletes electrolytes, especially potassium, sodium, and phosphorus. If left uncorrected, severe hyperglycemia can progress to hyperglycemic hyperosmolar nonketotic (HHNK) syndrome, a rare but potentially fatal condition. Advances in monitoring and delivery techniques have made HHNK an uncommon occurrence. Evidence that tight glucose control during PN greatly improves clinical outcome has made glycemic control a priority during PN therapy. The goal is to maintain blood glucose level no higher than 120 mg/dL for critically ill patients and no higher than 150 mg/dL for patients in stable condition receiving PN. Keeping dextrose infusion rates 4 mg/kg/min decreases the incidence of hyperglycemia. Patients with diabetes mellitus and those who are critically ill often need insulin to control blood glucose level during PN. Insulin is stable and is compatible with PN formulas, although a portion of the dose adheres to the administration bags and tubing. Guidelines typically call for 0.05 0.1 units of regular insulin for each gram of dextrose in the PN formula. For example, for an initial dextrose dose of 200 g, 10 20 units of insulin would be added to the PN formula. Closely monitor blood glucose level, and provide additional subcutaneous insulin coverage as needed. The insulin in the PN formula should be increased in increments of 0.05 units per gram of dextrose or by adding of the subcutaneous insulin coverage for the previous 24 h to the next PN formula until blood glucose level stays within target range. In cases of extreme hyperglycemia or insulin resistance, a separate continuous insulin drip allows greater flexibility in controlling glucose levels. After glycemic control is achieved, increase the dextrose dose 50 g/d, to maintain the same insulin to dextrose ratio. Hypoglycemia can develop in patients receiving PN formulas containing insulin. If the blood glucose level stays consistently < 80 100 mg/dL, reassess the insulin dose. This step is particularly necessary for patients with renal insufficiency, which delays insulin clearance, and for patients who are receiving tapering steroid doses. The following are guidelines for maintaining tight glucose control in patients receiving PN: | Blood Glucose Management with PN | | Goal: Aim for glucose level of 80 120 mg/dL in critically ill patients. Goal for blood glucose for stable patients ranges from 100 to 150 mg/dL. | | 1. Order fingerstick blood glucose measurement q6h, with sliding scale insulin coverage. | | 2. Use regular insulin. Do not use NPH or long-acting insulin to avoid fluctuation in blood glucose levels due to variation in drug action. | | 3. For patients with a history of diabetes or baseline blood glucose 120 150 mg/dL, limit initial dextrose dose to 150 g in PN. | | 4. For patients with baseline blood glucose 150 200 mg/dL, limit initial dextrose dose to 150 g and add insulin 0.1 units/g dextrose (15 units). | | 5. Review 24-h insulin coverage. Add two thirds of the insulin coverage to the next PN or increase insulin in PN by 0.05 units/g dextrose to a goal of 0.2 units/g dextrose. | | 6. Consider using an insulin drip for blood glucose levels persistently > 200 mg/dL. | | 7. Maintain the insulin/dextrose ratio when increasing or decreasing dextrose in PN. | | 8. Reassess insulin needs daily. Reduce insulin in PN 30 50% for blood glucose levels that drop below desired level. |
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Fluid and Electrolyte Disturbances: Candidates for PN often have preexisting nutritional deficits and nutrient losses due to GI disorders, which make fluid and electrolyte shifts especially common in this population. The principles of fluid and electrolyte management for patients receiving PN are similar to those for any patient. In cases in which fluid restriction is called for, PN formulas can contain the most concentrated form of the nutrients to reduce the volume of the solution. Hepatobiliary Complications: Abnormalities of hepatic function occur frequently in patients receiving PN. Early in therapy adults may have mild, transient elevations in liver enzymes that resolve when PN stops. However, neonates and patients receiving long-term PN may experience progressive, irreversible hepatic failure. Research findings show a strong association between excessive carbohydrate administration and liver dysfunction during PN. A number of additional risk factors have emerged, suggesting a multifactorial cause of PN-related hepatic dysfunction. PN also places recipients at risk of cholelithiasis, particularly patients who cannot tolerate any oral or enteral nutrition. Strategies for preventing and managing hepatic complications of PN include avoiding overfeeding, limiting dextrose dose to 30 50% of calories, providing 10 30% of calories as lipid, infusing PN over 12 16 h thus giving "time off" to mimic a postabsorptive state, and avoiding complete bowel rest if possible. Treatment with ursodeoxycholic acid may help patients with cholestasis. Pulmonary Complications: The CO2 produced by carbohydrate metabolism can place added stress on patients with CO2 retention and those who are being weaned from mechanical ventilation. To avoid problems related to CO2 production, the formula must meet, not exceed, the patient's requirements. In addition to avoiding overfeeding, reducing the carbohydrate dose and increasing the proportion of calories provided as fat can help prevent adverse pulmonary effects of PN. Catheter-Related Bloodstream Infection: PN increases the risk of catheter-related bloodstream infection (CR-BSI). Meticulous protocols for the insertion and maintenance of central venous catheters can greatly reduce the risk of this serious complication. CR-BSI may necessitate removal of the vascular access device or treatment with antibiotics, depending on the type of catheter, clinical status of the patient, and type of organism isolated from the patient's blood. Unexplained fever or elevated WBC count in a patient receiving PN should raise suspicion concerning CR-BSI. Terminating Therapy When oral or enteral intake resumes, patients should gradually receive fewer nutrients parenterally. Some clinicians infuse PN only at night in an effort to minimize the risk of rebound hypoglycemia, but no results of controlled trials exist to support this practice. There is rarely a need for a formal schedule of weaning from PN. If concerns about rebound hypoglycemia exist, a 5% dextrose solution can be infused after PN is discontinued. |
