Malnutrition (e.g., loss of significant lean body mass and/or depletion or frank deficiency of specific essential vitamins, minerals, and trace elements) is common in hospitalized patients and in patients unable to maintain adequate nutrition and hydration by the enteral route. Various factors contribute to protein-energy malnutrition and loss of micronutrients in these settings, including catabolic hormonal and cytokine signals, resistance to anabolic hormones, lack of adequate oral food intake during illness, abnormal nutrient losses (e.g., via drains, renal replacement therapies, wounds, emesis, polyuria), nil per os (NPO) status resulting from diagnostic or therapeutic tests and procedures, and increased macronutrient and micronutrient needs during specific illnesses.
Assessment of nutritional status requires comprehensive evaluation and integration of medical and surgical history, current clinical and fluid status, dietary intake patterns, body weight changes, physical examination, and selected biochemical tests. The gastrointestinal (GI; enteral) route should be the first choice for specialized feeding in the hospital setting, with parenteral nutrition (PN) modalities, via peripheral or central vein, reserved for those patients in whom adequate enteral nutrition (EN) is not possible. Thus, a key feature of nutritional assessment is determination of GI signs and symptoms that may preclude use of the enteral route for feeding (e.g., severe, nausea, emesis, diarrhea, partial or complete bowel obstruction, bleeding, fistulas). In such a minority of cases, feeding via the intravenous route by PN support may be indicated.
Current guidelines suggest that goals for caloric intake between 20 and 25 kcal/kg/day and for protein and amino acids between 1.2 and 1.5 g/kg/day are appropriate for most adult hospital patients. These goals can readily be met in most patients with the conventional PN methodologies outlined in the chapter. Adequate vitamins, minerals, electrolytes, essential amino acids, and essential fats must be provided, based on recommended allowances for healthy individuals; although the true requirements for these in subtypes of hospital patients are unknown, conventional PN provides all these substrates, in addition to fluid. Metabolic, infectious, and mechanical complications can occur with PN feeding modalities and can be prevented or diminished with careful monitoring and adherence to current standards of practice. Relatively few
rigorous, randomized controlled trials (RCTs) have been conducted in the field of specialized PN in the hospital setting, and many areas of uncertainty remain. However, numerous large, multicenter RCTs are in progress and will help to define more optimal use of this important adjunctive nutritional therapy over the next several years.
Vinnars and Wilmore and Bistrian summarized major historical aspects of PN therapy (1
). Intravenous administration of glucose was first described by Beidle and Krauts in 1896, intravenous administration of intravenous protein as fibrinogen hydrolysate was described by Elman in 1937, and the development of the first intravenous fat emulsion (Lipomul) in the United States occurred by 1960 (1
). Peripheral vein PN (PPN) using 5% or 10% glucose, protein hydrolysates, intravenous fat emulsions, electrolytes, and multivitamins was used from 1955 to 1965 by various clinicians for limited periods. Serious side effects led to withdrawal of intravenous Lipomul from the United States market in the early 1960s. This created a serious problem requiring that glucose be given either in large, relatively isotonic volumes for peripheral vein infusion or in hyperosmolar form requiring infusion into a major vein. Although central catheters threaded into veins had been used as early as 1944, they were uncommon. A safe and effective intravenous lipid preparation (Intralipid) had been developed by Wretlind in 1961 (2
) and approved for use in most European countries by 1963; it was not approved for use in Canada or in the United States until 1977. Intralipid availability in Europe in the early 1960s led to increased use of PN through peripheral veins (1
Widespread interest and increased use of PN occurred after publication of reports by Dudrick et al from the University of Pennsylvania in 1968 (3
). Using percutaneous central catheters to deliver nutrient solutions with glucose as the source of nonprotein calories, plus micronutrients (vitamins, mineral, trace elements), these investigators demonstrated convincingly that PN, as the sole source of nutrients, resulted in good growth in malnourished infants and positive nitrogen balance and nutritional and clinical improvement in malnourished adults over periods of many weeks (3
COMPARISON OF PERIPHERAL VEIN AND CENTRAL VEIN PARENTERAL NUTRITION
PN may be administered via a peripheral vein (PPN) or via a central vein (central vein parenteral nutrition [CPN]); CPN is typically infused through the subclavian or internal
jugular vein. Surprisingly, few rigorous clinical comparative effectiveness trial data are available on the efficacy of PPN, although anecdotally many nutrition support specialists feel that this therapy is quite useful for clinical stable non-ICU hospital patients who can tolerate the fluid load required to approach estimated energy and amino acid needs (17
). PPN may be useful for the patient who needs nutritional support for a short period of time and who has adequate peripheral veins; however, because of these limitations, many clinicians do not routinely prescribe this treatment (17
). The advantage of PPN is that it does not require the insertion and maintenance of a central venous catheter. In an attempt to minimize peripheral vein damage, 10% or 20% isotonic lipid emulsion as the main caloric source is substituted for the hypertonic glucose solutions typically used in CPN. A comparison of typical composition of PPN versus CPN is shown in Table 84.3
Electrolytes in PN are adjusted, as indicated, by GI losses, renal function changes, and other clinical parameters, coupled with serial monitoring of blood levels, to maintain serum or plasma levels within the normal range (6
). In the presence of elevated blood levels, lower doses (or elimination) of specific electrolytes in PN compared with the typical ranges listed in Table 84.3
for PPN and CPN, respectively, may be indicated until blood levels normalize. Higher dextrose concentrations in CPN typically increase potassium, magnesium, and phosphorus requirements, and doses of these nutrients are higher in CPN compared with PPN. In both PPN and CPN, the percentage of sodium and potassium salts as chloride can be increased to correct metabolic alkalosis, and the percentage of salts as acetate can be increased to correct metabolic acidosis (6
). Regular insulin can be added to PN as needed to maintain blood glucose concentrations into the goal range (typically between 140 and 180 mg/dL in the hospital setting). Both PPN and CPN provide all essential nine amino acids and several nonessential amino acids, with higher amino acid concentrations able to be provided via CPN (see later and Table 84.3
TABLE 84.3 COMPOSITION OF TYPICAL PARENTERAL NUTRITION FORMULATIONS
PERIPHERAL VEIN PARENTERAL NUTRITION
CENTRAL VEIN PARENTERAL NUTRITION
Amino acids (%)
a Conventional commercial preparations containing mixtures of essential vitamins and trace elements, respectively, are used in both peripheral and central vein parenteral nutrition (PN). Typical ranges are shown above, but amounts of specific components outside the ranges shown may be utilized in some cases. See text for additional details on PN composition.
In the United States, only soybean oil-based intravenous fat emulsions are available for use in PN (see later). Intravenous lipid is provided as a 20% emulsion when given as a separate infusion over 10 to 12 hours/day; when pharmacy PN compounders are used, 20% or 30% lipid emulsions may be mixed with dextrose, amino acids, and micronutrients in the same infusion bag (“all-in-one” total nutrient admixture PN solutions) (5
). In European and other countries, intravenous fish oil, olive oil, soybean oil/ medium-chain triglyceride (MCT) mixtures, and combinations of these are approved for use in PN (9
Trace elements added on a daily basis to PPN and CPN are mixtures of chromium (Cr3+
), copper, manganese (Mn2+
), selenium, and zinc. Minerals can also be supplemented individually. Vitamins added on a daily basis to PN are mixtures of vitamins A, B1
, C, D, and E, biotin, folate, and pantothenic acid (see later). Vitamin K may be present in some multivitamin preparations or added on an individual basis (e.g., in patients with cirrhosis). Specific vitamins can also be supplemented individually (6
A typical 2.5-L PPN preparation composed of 3% amino acids (4 kcal/g), 4% lipid (as a 20% lipid emulsion, 10 kcal/g), and 5% dextrose (3.4 kcal/g) provides 75 g amino acids (equivalent to 12 g of nitrogen) and 1725 calories, with an osmolality of approximately 600 mOsm/L. This osmolality is much less than a typical 1.5-L CPN solution that may be composed of 15% to 20% dextrose, 5% to 7% amino acids, and 3% to 4% lipid, which has higher osmolality of approximately 1700 mOsm/L; such high-osmolality CPN solutions cannot be infused through peripheral veins because of the development of phlebitis. PPN requires frequent (e.g., every 3 days) peripheral vein catheter changes to prevent thrombophlebitis. Some institutions use low-dose heparin infusion (e.g., 1000 units/bag PPN) and/or corticosteroids (e.g., 5 to 10 mg hydrocortisone/bag PPN) as a strategy to prevent phlebitis; however, this is not based on strong evidence to date.
As noted, the use of PPN necessitates significant fluid administration (e.g., 2 to 3 L/day) to provide adequate calories and amino acids in most patients. Given the low dextrose and amino acid concentrations in PPN, most calories are provided by the lipid emulsion. Stable hospital patients with body weights of 70 kg or less, however, can often be given amino acid and energy doses approaching estimated needs with as little as 2 L PPN/day. For example, if a 60-kg patient is estimated to require 25 kcal/ kg/day and 1.3 g amino acid/day to meet energy and amino acid needs, respectively (see later), then 25 kcal/kg × 60 kg body weight = a caloric goal of 1500 kcal/day and 1.2 g × 60 kg = a protein (amino acid) goal of 72 g amino acids/day. In such a patient, a 3% concentration of amino
acids in a 2-L PPN solution provides 60 g amino acids (1.0 g amino acid/kg/day), with 240 kcal/day derived from amino acid (4 kcal g); the typical dextrose concentration of 5% in PPN provides 100 g dextrose/2 L × 3.4 kcal/g = 340 kcal from dextrose, and the typical PPN lipid concentration of 4% provides 80 g lipid/2 L × 10 kcal/g = 800 kcal. Thus, such a 2-L PPN formulation provides 1.0 g amino acid/kg/day and 240 amino acid kcal + 340 dextrose kcal + 800 lipid kcal, for a total of 1380 kcal/day (or 23 kcal/kg/day).
Similar calculations can be used to determine proportions and percentages of amino acids, dextrose, and lipid to meet estimated goals when CPN is used. Thus, a typical 1.5 L/day infusion bag of CPN for a 60-kg patient containing 6% amino acids, 15% dextrose, and 3.5% fat emulsion provides 90 g amino acids (1.5. g amino acids/ kg/day), with 360 kcal/day coming from the amino acid (4 kcal/g); dextrose provides 225 g dextrose/1.5 L × 3.4 kcal/g = 765 kcal, and lipid at 4% provides 52.5 g lipid/1.5 L × 10 kcal/g = 525 kcal. Thus, such a 1.5 L CPN formulation provides 1.5 g amino acid/kg/day and 360 amino acid kcal + 756 dextrose kcal + 525 lipid kcal, for a total of 1641 kcal/day (or 27 kcal/kg/day). As shown earlier, providing sufficient energy by the central route in CPN without providing a large percentage as lipid necessitates infusing hypertonic glucose solutions (typically 10% to 20% dextrose; see Table 84.3
). Consequently, the catheter tip must be in a vessel with high blood flow causing rapid dilution; this minimizes the occurrence of phlebitis and thrombosis.
CATHETERS FOR PARENTERAL NUTRITION ADMINISTRATION
Numerous routes for such vascular access have been used; the most common are subclavian, jugular, and femoral veins. Central catheters placed via the subclavian vein are reported to have a lower bacterial colonization rate when compared with internal jugular or femoral vein approaches (19
Peripherally inserted central venous catheters (PICC lines) are used for intermediate period of PN (e.g., <30 days). If these types of catheters are used for PN, the tip of the catheter must be positioned in a central vein such as the superior or inferior vena cava. Kearns et al (20
) reported a significantly higher incidence of thrombosis and infection and decreased catheter survival when the tip of a PICC resided in the axillosubclavian-innominate vein compared with use of the superior vena cava. Cowl et al (21
) reported a higher rate of thrombosis and difficulty in placement when PICCs were compared with standard subclavian/internal jugular approaches.
Several reviews and guidelines on the prevention of catheter complications have been published (22
). In an effort to reduce the incidence of infection, tunneled central catheters were introduced in 1973. Not only are they associated with a lower risk of infection but also they can remain in place and functional for long periods of time. These are usually placed surgically within the subclavian or jugular vein, with the tip in the superior vena cava. The extravascular portion of the catheter is tunneled before being brought out through the skin. The catheter is typically anchored at the skin exit with a Dacron cuff, which eliminates the need for sutures in the skin and also acts as a barrier to bacteria (22
). In another method, chambers of silicone or other elastomers, termed ports, are implanted subcutaneously. The chamber is connected by a catheter, usually placed into the subclavian vein with its tip in the superior vena cava (24
). Nutrient solution is infused into the chamber via special needles inserted through the skin.
Insertion and use of an indwelling central venous catheter pose various risks to the patient, including pneumothorax, hemothorax, thrombosis, infection, vascular or nerve injury, hypersensitivity reactions, and microbial contamination. Reported complication rates range from 0.3% to 12% and vary according to definition of complications, physician expertise, preparation used, frequency of manipulation of the catheter, and other factors (25
). Thrombogenicity varies with the catheter material; the earlier and stiffer polyvinyl and polyethylene catheters were associated with more thrombus formation than silicone or polyurethane catheters. Multilumen catheters have increased in use, and they provide additional access for infusing medications and blood and for blood sampling without interfering with PN administration. There are conflicting reports about the frequency of catheter-related sepsis (26
). Placement site is related to infection rates (e.g., femoral and jugular sites tend to have higher rates than the subclavian site) (27
). Similarly, catheter tunneling (e.g., jugular) reduces the incidence of line sepsis (28
) and also reduces other problems such as dislodgment.
Several additional approaches have been adopted in an attempt to prevent catheter-related bloodstream infections (BSIs) in patients receiving short-term and long-term CPN (29
). These include the use of strict catheter insertion and maintenance protocols; appropriate hand hygiene and aseptic technique with catheter insertion and manipulation; use of tunneled, cuffed CPN catheters for more chronic PN infusions (e.g., in home patients requiring CPN); avoidance of femoral vein catheters; and use of various types of catheters impregnated with antimicrobial agents or chlorhexidine (29
). Other interventions associated with decreased BSIs (not conclusively proven) are various catheter site dressing with antibiotic or antiseptic ointments and catheter locks containing heparin, vancomycin, citrate, taurolidine, or ethanol (29
All types of complications, not just infectious, have also been shown to be less frequent when experienced personnel (preferably members of a nutrition support team) exercise necessary precautions, including using an aseptic technique in catheter insertion and maintenance,
checking proper placement by radiographic study before use, and adequately caring for the insertion site. The use of ultrasound may facilitate central line placement. It reduces the number of failed insertion attempts and overall mechanical complication rates, particularly in the hands of inexperienced personnel, but it does not seem to decrease insertion time significantly (34
). In 2011, the US Centers for Disease Control and Prevention published new comprehensive guidelines for the prevention of intravascular catheter-related infection (35
Nutrient solutions for PN are delivered exclusively from plastic bags via electronic pumps. CPN solutions are generally delivered using peristaltic pumps of various types. These have become increasingly sophisticated, automated, and expensive. They ensure even flow rates, overcome the increased resistance of filters of small porosity (especially with continued use), minimize the likelihood of clotting at the catheter tip, and reduce the need for frequent nursing surveillance. Most have an air-in-line alarm system that prevents the occurrence of air embolism.
The use of pliable plastic bags of various sizes eliminates the danger of breakage, simplifies transportation and storage, and reduces storage space requirements before and after filling compared with use of glass or formed-plastic bottles. The usual water solutions of nutrient formulations do not extract measurable amounts of phthalate plasticizer used in the manufacture of polyvinyl chloride (PVC) bags; however, albumin, lipids, and blood take up the plasticizer (36
). The amount of plasticizer eluted from PVC administration sets by lipid emulsions is relatively small compared with that from the bags. Plasticizer-free ethylene vinyl acetate tubing and bags have essentially replaced products using PVC.
Dual-chambered plastic bags that allow admixture of macronutrients immediately before infusion of PN are available. These are very convenient for home PN (HPN) use, especially for patients who receive intravenous lipids on a regular basis. Dual-chambered bags are manufactured either empty or with the macronutrients in them (i.e., dextrose in one chamber and amino acids in the other chamber). When lipid is used, the dextrose, amino acids, and electrolytes are added to the bottom chamber of the empty bag and the desired intravenous lipid dose to the upper chamber. Before administration, the plastic divider is removed, and the admixture with lipid is prepared. This increases stability because the total nutrient admixture (TNA) is not prepared until just before infusion.
Filters continue to be recommended during administration of PN formulations (37
). In general, filters remove or reduce the infusion of particulate matter, air, and microorganisms into the patient. Particulates are found in large-volume injectables. Particulates have been found to clog pulmonary capillaries and actually cause pulmonary embolus when they exceed 5 μm. Potentially, they could also deposit in other soft tissues such as the brain, spleen, renal medulla, and lung. For those centers that use PPN, in-line filters have been reported to decrease the incidence of phlebitis (5
). The two filters used commonly during administration of PN formulations are 0.22- and 1.2-μm filters. The 0.22-μm filter is effective at removing microorganisms, particulates, and air. A 0.22-μm filter with a nylon membrane that has been positively charged has the ability to remove pyrogen (e.g., Gram-negative endotoxin) by electromagnetic forces (5
). TNAs should be filtered with 1.2-μm filters because the lipid particles in a stable emulsion are between 0.1 and 1 μm in size. Although lipid particles could be forced through a 0.22-μm filter, it would destabilize the emulsion. The 1.2-μm filter removes organisms such as Candida albicans
because they are large particles in the range of 3 to 6 μm. Patients who receive HPN will have several bags of PN stored in a home refrigerator to enhance compatibility before administration. These patients should be taught to remove the PN formulation 2 to 3 hours before administration so the product is closer to room temperature during infusion.
Insulin adsorption to the catheter varies appreciably depending on the binding characteristics of the nutrients present, the type of plastic in the delivery system, the presence of filters, and the concentration of insulin added (5
). Insulin adsorption is minimal in TNAs. When insulin is added to PN formulations for diabetic patients, the dosage must be closely monitored until properly adjusted (5