Parenteral Nutrition1
Rex O. Brown
Gayle Minard
Thomas R. Ziegler
1Abbreviations: AMA, American Medical Association; ASPEN, American Society for Parenteral and Enteral Nutrition; BSI, bloodstream infections; CPN, central vein parenteral nutrition; Cr3+, chromium; EFA, essential fatty acid; EN, enteral nutrition; ESPEN, European Society for Parenteral and Enteral Nutrition; FDA, Food and Drug Administration; FFA, free fatty acid; GI, gastrointestinal; GSHPx, glutathione peroxidase; HPN, home parenteral nutrition; ICU, intensive care unit; LBW, low birth weight; LCT, long-chain triglyceride; MCT, medium-chain triglyceride; Mn2+, manganese; MVI, multiple vitamin infusion PICC, peripherally inserted central venous catheter; PN, parenteral nutrition; PPN, peripheral vein parenteral nutrition; PVC, polyvinyl chloride; RCT, randomized controlled trial; RES, reticuloendothelial system; TNA, total nutrient admixture.
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.
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.
HISTORICAL ASPECTS
Vinnars and Wilmore and Bistrian summarized major historical aspects of PN therapy (1, 2). 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, 2).
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).
CLINICAL PRACTICE GUIDELINES
After the early reports of successful use of CPN, coupled with reports that malnutrition was common in hospital patients, its use expanded rapidly in the clinical practice of nutrition support in patients unable to be adequately fed enterally. Many institutions that used PN frequently developed multidisciplinary nutrition support teams, typically consisting of physicians, dieticians, nurses, and pharmacists. The American Society for Parenteral and Enteral Nutrition (ASPEN) was formed in 1978, and one of its goals was to promote the safe and efficacious use of specialized nutrition support (PN and EN). The first set of clinical guidelines for the use of specialized nutrition support was published by ASPEN in 1993 (4). A revision of these guidelines that provided a markedly increased depth and scope of nutrition support practice was published in 2002 (5). A National Advisory Group of ASPEN published a report on safe practices for PN formulations in 1998; a revision of these guidelines was published in 2004 (6). ASPEN (http:// www.nutritioncare.org) more recently published a variety of new guidelines for use of specialized nutrition in patients with critical illness and other conditions (7, 8). Similarly, the European Society for Parenteral and Enteral Nutrition (ESPEN; http://www.espen.org) has published clinical practice guidelines on use of PN in several conditions (9); the Canadian Critical Care Clinical Practice Guidelines Committee publications relate to PN use in critical illness (http://www.criticalcarenutrition.com) (10).
NOMENCLATURE
Various descriptive terms have been applied to the procedure used in supplying nutrition support. The term “hyperalimentation” entered the clinical nutritional lexicon in various ways to indicate the need for large amounts of calories and certain other nutrients. Both historically and etymologically, hyperalimentation has implied needing and providing amounts of nutrients that exceed normal requirements (particularly for energy and amino acids). It is now clear that, used in this way, the term has a potentially misleading connotation because provision of excess energy and certain nutrients is often undesirable, as outlined later. For this reason, the term is no longer used. It was replaced by the designation total PN (TPN) and, more recently, by the general designation of PN, given that many patients receiving PN also receive at least a portion of their nutrient intake by the enteral route.
INDICATIONS
The primary objective of PN is maintaining or improving the nutritional and metabolic status of patients who, for a critical period of time, cannot be adequately nourished by oral or tube feeding (EN) (Table 84.1). The value and use of this treatment method in the management of patients with specific clinical problems are also discussed in
relevant chapters in this book and in the ASPEN, ESPEN, and Canadian Clinical Practice Guidelines (5, 6, 7, 8, 9, 10). Normal nutritional requirements for adults and children are cited, as well as specific recommendations for nutrition support throughout the life cycle and diseases frequently encountered in patient populations.
relevant chapters in this book and in the ASPEN, ESPEN, and Canadian Clinical Practice Guidelines (5, 6, 7, 8, 9, 10). Normal nutritional requirements for adults and children are cited, as well as specific recommendations for nutrition support throughout the life cycle and diseases frequently encountered in patient populations.
TABLE 84.1 COMMON INDICATIONS FOR USE OF PARENTERAL NUTRITION | ||||||
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The decision to undertake PN requires weighing various factors and considering the patient’s diagnosis and prognosis, as discussed in the relevant chapters. It is not a defensible substitute for oral or tube feeding when adequate provision by either of these methods is feasible. Most (>85% to 90%) hospitalized patients, including those in the intensive care unit (ICU) setting, can be fed enterally via oral diet, oral nutrient supplements, and/or gastric or intestinal tubes. However, in approximately 10% to 15% of hospital patients deemed to require specialized nutrition support, EN is contraindicated; and these patients are routinely given PN, via a peripheral vein, or commonly in ICU patients, via a central vein (5, 6, 7).
The common conditions for use of PN, listed in Table 84.1, are generally accepted indications around the world. Therapeutic effects of PN occur via the combined provision of calories (primarily as the dextrose and lipid components, with a smaller contribution from the amino acids provided), essential fatty acids (EFAs), essential and nonessential amino acids, vitamins, minerals, and trace elements (6). These support vital organ and cell functions, immunity, protein synthesis, skeletal and respiratory muscle capacity, wound healing, and tissue repair. However, the use of PN in a variety of other conditions is often controversial because of the paucity of appropriate studies that give statistically valid data supporting or negating the value of PN in specific situations (i.e., although lifesaving to provide essential nutrients when the enteral route is not available, there is a rather weak evidence base for commonly used PN therapeutic approaches).
PN is clearly adjunctive treatment in most cases. For example, an earlier metaanalysis of PN in critically ill patients demonstrated that PN did not affect mortality in this population, but it did decrease complication rates, especially in undernourished patients (11). Some of the data that reflect negatively on PN may have more to do with overfeeding or PN-induced hyperglycemia than harm actually caused by the use of PN itself. Rigorous studies have begun to address the many controversies remaining with regard to appropriate timing and composition of PN in various patient subgroups, particularly in critically ill patients (12, 13, 14, 15, 16).
Despite the routine use of PN in many clinical settings around the world (e.g., in ICU and non-ICU hospital settings, in home patients with short bowel syndrome or other forms of intestinal failure), many areas of uncertainty with regard to the optimal use PN remain, given the current lack of rigorous comparative effectiveness research in large, well-powered patient populations (Table 84.2) (15, 16). Problems with these earlier PN studies include small sample sizes, uncertain or heterogeneous study subject characteristics (including varying definitions of illness severity), and inappropriate or inadequate blinding (6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16). In addition, the PN dextrose and calorie doses used in most of the earlier trials (from the 1980s to 1990s) would currently be considered excessive and/ or resulted in hyperglycemia, now appreciated as a major risk factor for ICU morbidity and mortality (13, 14, 15).
TABLE 84.2 CURRENT AREAS OF UNCERTAINTY REGARDING USE OF PARENTERAL NUTRITION | |||||||||
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Generally accepted, although not evidence-based, contraindications for PN are as follows: when the GI tract is functional, and access for enteral feeding is available; when PN is unlikely be required for more than 5 to 7 days with GI function expected to normalize, if the patient cannot tolerate the intravenous fluid load required for PN; when the patient has severe hyperglycemia or marked electrolyte abnormalities at the time initiation of PN is planned; and if new placement of a central venous catheter solely for PN is deemed to pose undue risks (6, 15).
Compared with PN, EN is less expensive, may better maintain intestinal mucosal structure and gut absorptive and barrier functions (as clearly shown in animal studies), and is associated with fewer mechanical, metabolic, and infectious complications (15). Therefore, after starting PN, it is standard practice for EN to be initiated with the return of adequate GI function and advanced as tolerated and the amount of administered PN correspondingly reduced.
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, 18). 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, 18). 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.
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, 18). 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, 18). 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, 7). 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 | |||||||||||||||||||||||||||||||||||||
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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, 6, 7, 8). 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 (thiamin), B2 (riboflavin), B3 (niacinamide), B6 (pyridoxine), B12, 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).
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, 23). 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, 23). 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, 27). 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, 30, 31, 32, 33). 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, 30, 31, 32, 33). 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, 30, 31, 32, 33).
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).
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).
DELIVERY SYSTEMS
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, 6). 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, 6). 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, 38, 39).
COMPONENTS AND REQUIREMENTS
Fluid
Fluid requirements for most adult are approximately 30 to 40 mL/kg/day (6). The fluid component of PN plus other intravenous fluids with or without any enteral fluid intake must meet individual requirements as determined by evaluation of the clinical and laboratory data (e.g., physical examination findings relevant to fluid status and plasma sodium and urea concentrations). Consideration of the close interrelationships of water, electrolytes, hormonal factors, and organ function is very important when prescribing a PN formulation. In addition to clinical factors that could cause excessive retention or loss, consideration must be given to fluid intake with medications and “keepvein-open” infusions, as well as changes in insensible water loss. Meticulous recording of fluid intake and output is necessary. Assessment of volume status by hemodynamic monitoring may be required in some critically ill patients.
Standard PN admixtures can be administered to the patient with increased fluid needs, especially when extra renal losses are involved, with a supplemental intravenous solution to meet needs in the acute care setting. In the home setting, the extra fluid requirements can be added to the PN admixture in one plastic bag or can be given separately. For the patient who is fluid overloaded, the PN
prescription should be made as concentrated as possible to minimize intake. Expansion of extracellular fluid is common in hospitalized patients with malnutrition, and this increases body weight and decreases serum concentrations of albumin, prealbumin, and other proteins, independent of nutritional status.
prescription should be made as concentrated as possible to minimize intake. Expansion of extracellular fluid is common in hospitalized patients with malnutrition, and this increases body weight and decreases serum concentrations of albumin, prealbumin, and other proteins, independent of nutritional status.
Energy and Macronutrient Requirements
Caloric goals in clinically stable, noncritically ill adult patients are estimated by current clinical practice guidelines at approximately 25 to 30 kcal (6.0 to 7.2 kJ)/kg body weight/day. A ratio of grams of nitrogen to kilocalories (N/kcal) of approximately 1:130 to 150 (1:31 to 36 N/kJ) is a routinely prescribed formula in stable non-ICU patients (5, 6). Shaw et al (40) developed a graphic presentation of the effects of nitrogen and energy intakes on nitrogen and fat balance in depleted patients. The amount of additional protein needed is usually proportionally higher than that of energy; for example, for adult patients acutely stressed by trauma, burns, or infection, the N/kcal ratio is commonly increased (e.g., 1:100). In ICU patients, precise caloric needs for improved clinical outcomes remain unclear, but lower doses (e.g., 20 to 25 kcal/kg/day) are recommended by European and American-Canadian clinical practice guidelines, given the risks associated with higher caloric loads in the ICU setting (see later) (7, 9, 14, 15). The energy goals for infants and children requiring PN are based on age and other factors and are beyond the scope of this chapter, but they have been reviewed in ASPEN guidelines (8, 41).
Currently, several RCTs are in progress to define clinically optimal PN calorie doses in ICU and non- ICU patients more accurately (16). Even though precise energy, protein and amino acid, caloric, fat, and micronutrient needs in the types of patients requiring PN are not well defined by rigorous data, conventional guidelines, based on decades of experience with PN administration, appear to be generally safe and effective for most patients (Table 84.4) (6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16).
Amino Acids
As noted earlier, conventional PN formulations provide all nine essential amino acids and a variety of nonessential amino acids, with the exact amino acid proportion and amount or volume varying as a function of the specific commercial preparation (Table 84.5). Intravenous amino acid solutions have evolved from the original hydrolysates of casein or blood fibrin to formulations of crystalline L-amino acids of different compositions and varying concentrations based in part on the amino acid composition of high-quality dietary proteins. Formulations of crystalline L-amino acids have been developed for specific clinical problems, with varying claims for superiority over more general formulas for use in renal and hepatic failure, in trauma, and for growth of infants (4, 5, 6, 7, 8). Commercial formulations differ among and within manufacturers in amino acid composition and concentrations, depending on clinical purpose; in addition, they may have added electrolytes and/or glucose. Concentrated standard amino acids in a 15% and 20% solution are now available for patients who are fluid overloaded and require PN. Many pharmacies that use automated compounders will stock one strength (usually 15% or 20%) of standard amino acids to make all PN formulations using this component (5, 6).
TABLE 84.4 GENERAL GUIDELINES FOR MACRONUTRIENT DOSING IN ADULT HOSPITAL PATIENTS | |||||||||||||||||||||||||||||||||
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The typical recommended dose of amino acids for adults is 1.2 to 1.5 g kg/day, but in special circumstances, such as with continuous renal replacement therapy or burn injury (see the chapter on burns and wound healing), higher amino acid doses (approaching 2 g kg/day) have been recommended by some (42, 43). Higher PN amino
acid doses are also required for infants and growing children (8). The amino acid load in PN is adjusted downward or upward as a function of the amino acid dosing goal and as a function of the degree of renal and hepatic dysfunction, respectively (6, 7, 8, 15). Some guidelines recommend routine addition of glutamine as a conditionally essential amino acid in ICU patients (see the chapter on glutamine) (9). Although it is not questioned that essential and sufficient nonessential amino acids should be provided in PN in amounts needed to sustain adequate protein synthesis and intermediary metabolism, surprisingly, limited data from rigorous, adequately powered RCTs to define optimal doses of total or individual amino acids in PN are available (44, 45). Although some promising data have been published, little rigorous data are available on clinical efficacy of altered doses of specific amino acids in PN, including arginine, branched-chain amino acids, cysteine, or taurine supplementation (45).
acid doses are also required for infants and growing children (8). The amino acid load in PN is adjusted downward or upward as a function of the amino acid dosing goal and as a function of the degree of renal and hepatic dysfunction, respectively (6, 7, 8, 15). Some guidelines recommend routine addition of glutamine as a conditionally essential amino acid in ICU patients (see the chapter on glutamine) (9). Although it is not questioned that essential and sufficient nonessential amino acids should be provided in PN in amounts needed to sustain adequate protein synthesis and intermediary metabolism, surprisingly, limited data from rigorous, adequately powered RCTs to define optimal doses of total or individual amino acids in PN are available (44, 45). Although some promising data have been published, little rigorous data are available on clinical efficacy of altered doses of specific amino acids in PN, including arginine, branched-chain amino acids, cysteine, or taurine supplementation (45).
TABLE 84.5 COMPOSITION OF COMMERCIAL AMINO ACID PRODUCTS FOR PARENTERAL NUTRITION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adequate EFAs should be supplied, and conventional intravenous lipid emulsions provide adequate linoleic and α-linolenic fatty acids; generally more than 3% of total kilocalories provided as EFAs are required to prevent EFA deficiency (see later). All essential electrolytes, trace elements, and vitamins are provided in conventional complete PN, but optimal intakes of specific micronutrient intakes to meet individual needs in clinical settings are essentially unknown, and more data are needed. Clinically, a reasonable approach is to maintain specific micronutrients, when measured, within the normal plasma concentration range. Deficiency of an essential nutrient may lead to negative nitrogen balance. For example, single deficiency of potassium, sodium, phosphate, or nitrogen impairs or abolishes retention of other elements, and zinc depletion can itself cause negative nitrogen balance (46, 47).
Carbohydrates
Glucose (dextrose) is the commonly used carbohydrate for caloric contribution in PN and is usually the major source of energy, typically ordered as 60% to 70% of the total
PN non-amino acid calories (see Table 84.4). Parenteral glucose is in the form of the monohydrate, with 1 g providing approximately 3.4 kcal. It is readily available in various concentrations in liquid form, is relatively inexpensive, and is rapidly metabolized by most patients. Using primarily glucose to meet large energy needs within a tolerable fluid volume requires an extremely hypertonic solution (Table 84.6).
PN non-amino acid calories (see Table 84.4). Parenteral glucose is in the form of the monohydrate, with 1 g providing approximately 3.4 kcal. It is readily available in various concentrations in liquid form, is relatively inexpensive, and is rapidly metabolized by most patients. Using primarily glucose to meet large energy needs within a tolerable fluid volume requires an extremely hypertonic solution (Table 84.6).
TABLE 84.6 OSMOLALITIES AND ENERGY VALUES OF INTRAVENOUS DEXTROSE PREPARATIONSa | |||||||||||||||||||||
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Glucose Metabolism and Hormonal Changes
Infusion of intravenous glucose into humans results in an increase in insulin secretion, thus leading to increased insulin serum concentrations. In stable patients, this adaptive response is often adequate for maintaining normal or nearly normal serum concentrations of glucose. Abrupt cessation of PN can result in rebound hypoglycemia in some patients because the secretion of insulin is not blunted immediately with the withdrawal of the PN infusion. Therefore, clinical practice dictates that intravenous dextrose (usually 5% or 10%) be administered after withdrawal of PN to prevent hypoglycemia, unless the patient is eating some carbohydrate-containing food or is being tube fed (48). Adaptation to increasing loads of parenteral glucose and other nutrients decreased as the duration of infusion was shortened in test subjects, who were relatively stable adults being prepared for or already receiving HPN (49). Because such patients are not uncommon, tolerance to glucose must be checked before large amounts are infused in cyclic fashion. Other studies in adults found that abrupt termination of PN was rarely associated with significant hypoglycemia or its symptoms (50). ASPEN clinical guidelines on preventing hyperglycemia and hypoglycemia in the neonate receiving PN have been published (51). Sudden increases or decreases in glucose infusion can be averted by the use of infusion pumps that can gradually increase infusion of the admixture and taper it automatically, without changing the pump settings.
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