Michael D. Kraft and Imad F. Btaiche
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. List the appropriate indications for the use of parenteral nutrition (PN).
2. Describe the components of PN and their role in nutrition support therapy.
3. List the elements of nutrition assessment and factors considered in assessing a patient’s nutritional status and nutritional requirements.
4. Explain the pharmaceutical and compounding issues with PN admixtures.
5. Develop a plan to design, initiate, and adjust a PN formulation based on patient-specific factors.
6. Describe the etiology and risk factors for PN macronutrient-associated complications including hyperglycemia, hypoglycemia, hyperlipidemia, and azotemia in patients receiving PN.
7. Describe the etiology and risk factors for the refeeding syndrome.
8. Describe the etiology and risk factors for liver complications and metabolic bone disease in patients receiving PN.
9. Design a plan to monitor and correct fluid, electrolyte, vitamin, and trace element abnormalities in patients receiving PN.
10. Design a plan to assess the efficacy and monitor the safety of PN therapy.
KEY CONCEPTS
Parenteral nutrition (PN), also called total parenteral nutrition (TPN), is the IV administration of fluids, macronutrients, electrolytes, vitamins, and trace elements for the purpose of weight maintenance or gain, to preserve or replete lean body mass and visceral proteins, and to support anabolism and nitrogen balance when the oral/enteral route is not feasible or adequate.
Amino acids are provided in PN to preserve or replete lean body mass and visceral proteins, and to promote protein anabolism and wound healing.
Dextrose (D-glucose) is the major immediate energy source in PN and is vital for cellular metabolism, body protein preservation, tissue formation, and cellular growth.
IV lipid emulsions are used as an energy source in PN, and to prevent or treat essential fatty acid deficiency.
PN should not be used to treat acute fluid and electrolyte abnormalities. Rather, PN should be adjusted to meet maintenance requirements and to minimize worsening of underlying fluid and electrolyte disturbances.
Electrolytes, vitamins, and trace elements are essential for numerous biochemical and metabolic functions, and should be added to PN daily unless otherwise not indicated.
PN can be administered via a small peripheral vein (as peripheral PN [PPN]) or via a larger central vein (as central PN).
PN admixtures can be prepared by mixing all components into one bag [3-in-1 admixture or a total nutrient admixture (TNA)] or by mixing and infusing dextrose, amino acids, and all other components together (2-in-1 admixture) and infusing IV lipid emulsion separately.
PN can be associated with significant complications with both short-and long-term therapy.
Patients receiving PN should have specific laboratory values checked to assess electrolyte status, organ function, and nutritional status, and these parameters should be monitored as indicated clinically.
INTRODUCTION
Maintaining adequate nutritional status, especially during periods of illness and metabolic stress, is an important part of patient care. Malnutrition in hospitalized patients is associated with significant complications, including increased infection risk, poor wound healing, prolonged hospital stay, and increased mortality, especially in surgical and critically ill patients.1 Nutrition support therapy refers to the administration of nutrients via the oral, enteral, or parenteral route for therapeutic purposes.1 
Parenteral nutrition (PN), also called total parenteral nutrition (TPN), is the IV administration of fluids, macronutrients, electrolytes, vitamins, and trace elements for the purpose of weight maintenance or gain, to preserve or replete lean body mass and visceral proteins, and to support anabolism and nitrogen balance when the oral/enteral route is not feasible or adequate. PN is a potentially lifesaving therapy in patients with intestinal failure, but also may be associated with significant complications.
DESIRED OUTCOMES AND GOALS
Nutrition support therapy is aimed at meeting patient’s nutritional requirements, improving energy and net protein balance, promoting growth or weight maintenance, and improving healing, particularly in malnourished patients. Goals of providing nutrition support therapy include:
• Weight maintenance (potential weight gain in malnourished patients and growing children) Preservation (or repletion) of lean body mass and visceral proteins
• Support of anabolism and nitrogen balance
• Correction or avoidance of fluid and electrolyte abnormalities
• Correction or avoidance of vitamin and trace element abnormalities
• Avoidance of further nutritional deficiencies
Indications for PN
PN can be a lifesaving therapy in patients with intestinal failure, but the oral or enteral route is preferred when providing nutrition support therapy (“when the gut works, use it”). Compared with PN, enteral nutrition is associated with lower risk of hyperglycemia and fewer infectious complications (e.g., pneumonia, intra-abdominal abscess, and catheter-related infections).1,2 However, if used appropriately (i.e., in patients with altered intestinal function or when the intestine cannot be used), PN can be safe, effective, and improves nutrient delivery.3 Indications for PN are listed in Table 100–1.1,2 More detailed recommendations on appropriate PN indications in specific disease states, as well as when to initiate PN, can be found in the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Guidelines for the Use of Parenteral and Enteral Nutrition.1 More recently, A.S.P.E.N. and the Society of Critical Care Medicine (SCCM) published detailed guidelines for nutrition support therapy in critically ill adult patients, including patients undergoing major upper GI surgical procedures.2
Table 100–1 Indications for PNa,b
• Bowel obstruction
• Physical/mechanical (e.g., tumor compressing intestinal lumen)
• Functional (e.g., postoperative ileus)
• Major small bowel resection (e.g., short-bowel syndrome)
• Adult patients with less than 100 cm small bowel distal to the ligament of Treitz without a colon
• Adult patients with less than 50 cm of small bowel if the colon is intact
• Diffuse peritonitis
• GI fistulas if enteral nutrition cannot be provided above or below the fistula
• Pancreatitis—if patients have failed enteral nutrition beyond the ligament of Treitz or cannot receive enteral nutrition (e.g., due to intestinal obstruction)
• Severe intractable vomiting
• Severe intractable diarrhea
• Preoperative nutrition support in patients with moderate to severe malnutrition who cannot tolerate enteral nutrition and in whom surgery can be delayed safely for at least 7 days
a When anticipated that adequate oral or enteral nutrition will not be possible for approximately 7 days or more, and if anticipated that PN will be used for approximately 7 days or more.
b In patients with evidence of malnutrition, nutrition support therapy should be initiated as soon as possible (e.g., within 24–48 hours of hospital admission) after the patient has been resuscitated.
From Refs. 1 and 2.
PN COMPONENTS
PN should provide a balanced nutritional intake, including macronutrients, micronutrients, fluid and electrolytes. Macronutrients, including amino acids, dextrose, and IV lipid emulsions, are important sources of structural and energy-yielding substrates. A balanced PN formulation of total daily calories includes 10% to 20% from amino acids, 50% to 60% from dextrose, and 20% to 30% from IV lipid emulsion. Under conditions when patients have higher protein requirements (e.g., severe thermal injury, treatment with continuous renal replacement therapy, hypocaloric feeding—discussed later), amino acids may provide slightly more than 20% of the total daily calories. Electrolytes and micronutrients including vitamins and trace elements are required to support essential biochemical reactions. PN also provides a significant source of fluids. Patients require individual adjustments of PN components based on their nutritional status, nutritional requirements, underlying disease state(s), level of metabolic stress, clinical status, and organ functions.
Amino Acids
Amino acids are the building blocks of body proteins. There is no excess storage form of protein in the body, so amino acids are an essential component of the PN admixture.
Amino acids are provided to preserve or replete lean body mass and visceral proteins and to promote protein anabolism and wound healing. Amino acids are a source of calories with a caloric value of 4 kcal/g.
Patient Encounter 1
AA is 45-year-old woman admitted to the hospital with chief complaints of fever, abdominal pain, nausea, and vomiting for 2 days. She also reports decreased appetite and decreased oral intake for the past 3 to 4 days. AA was discharged from the hospital 2 weeks ago after having a small bowel resection for recurrent bowel obstruction.
Medical History
Recurrent intestinal strictures, intestinal obstructions, type II diabetes mellitus
Surgical History
Small bowel resections (less than 100 cm of small intestine remaining, ileocecal valve and colon intact)
Family History and Social History
Noncontributory
Medications Prior to Admission
Glipizide XL 5 mg orally daily
PE:
Height 168 cm (approximately 5 ft, 6 in.), actual body weight 60 kg (132 lb), ideal body weight 60 kg (132 lb), temperature 38.9°C (102°F), heart rate 98 bpm, blood pressure 98/55 mm Hg, respiratory rate 30 breaths/min, alert and oriented × 3, mucous membranes and skin appear cool and dry, tachycardic, tachypneic, lungs clear Abdomen: slightly tense, diffuse abdominal pain CT: evidence of interperitoneal free air consistent with perforation.
Diagnoses
Possible intestinal leak/perforation, diffuse peritonitis, sepsis, mild dehydration, and hypovolemic hypotonic hyponatremia
Plan
Admit to the surgical intensive care unit for resuscitation and treatment.
Is PN therapy indicated in this patient?
What other patient data should be collected to help formulate a PN prescription?
Parenteral crystalline amino acid bulk solutions are supplied by various manufacturers in various concentrations (e.g., 3.5%, 5%, 7%, 8.5%, 10%, 15%, and 20%). Different formulations are tailored for specific age groups (e.g., adults and infants) and for some disease states (e.g., kidney and liver disease). Specialized formulations for patients with acute kidney injury contain higher proportions of essential amino acids. Formulations for patients with hepatic encephalopathy contain higher amounts of branched-chain and lower amounts of aromatic amino acids. However, these specialized formulations are not used routinely in clinical practice because their efficacy and role in improving patient outcomes has not been clearly demonstrated. Crystalline amino acid solutions have an acidic pH (pH ≈ 5 to 7) and may contain inherent electrolytes (e.g., sodium, potassium, acetate, and phosphate).
Dextrose
Dextrose (D-glucose) is the major immediate energy source, and it is vital for cellular metabolism, body protein preservation, and cellular growth. Several body tissues depend primarily on dextrose for energy, including the central nervous system (CNS), red blood cells, and the renal medulla.
Parenteral dextrose (hydrous dextrose) used in PN compounding typically is provided as a 70% stock solution (70 g/100 mL), although some institutions use a 50% stock solution. The final dextrose concentration in the central PN solution typically should not exceed 35%. Hydrous dextrose provides 3.4 kcal/g (14.2 kJ/g). A dextrose infusion rate of 2 mg/kg/min in adult patients is sufficient to suppress gluconeogenesis and spare body proteins from being used for energy.4 Continuous dextrose infusion rate in hospitalized adult patients generally should not exceed 4 to 5 mg/kg/min.5,6
IV Lipid Emulsions
IV lipid emulsions have two main clinical uses: prevent or treat essential fatty acid deficiency and provide an energy source. IV lipid emulsions currently marketed in the United States consist of long-chain triglycerides. Lipid particles consist of a triglyceride core surrounded by a layer of egg phospholipids (emulsifiers). These particles carry a negative charge on their surface that creates repulsive electrostatic forces between droplets and maintains the stability of the emulsion. Glycerol is added to the emulsion to adjust the tonicity, and water is the solvent. The negative charges on the surface of lipid particles can be disrupted by cations, especially divalent cations such as calcium and magnesium, iron which can exist in divalent or trivalent form,7 and extreme pH changes, particularly acidic pH. Creamingof the emulsion occurs when lipid particles begin to aggregate and migrate to the surface of the emulsion, but can be reversed with mild agitation. If these particles continue to aggregate, coalescence may occur and destabilize the emulsion. A coalesced emulsion should not be infused into a patient because this can result in fat emboli. If coalescence continues, irreversible separation of the emulsion can occur (oiling out or breaking of the emulsion).
Table 100–2 Comparison of IV Lipid Emulsions
IV lipid emulsions differ in their concentration (10%, 20%, and 30%), caloric density, natural source of lipids, and ratio of phospholipids to triglycerides (PL:TG). Table 100–2 shows a comparison of commercially available IV lipid emulsions in the United States. The 10%, 20%, and 30% lipid emulsions provide 1.1 kcal/mL (4.6 kJ/mL), 2 kcal/mL (8.4 kJ/mL), and 3 kcal/mL (12.6 kJ/mL). The 10% and 20% lipid emulsions have a PL:TG ratio of 0.12 and 0.06, respectively; the 30% lipid emulsions have a PL:TG ratio of 0.06 (30% Liposyn III) or 0.04 (30% Intralipid). The lower PL:TG indicates a lower phospholipid content and translates to a better clearance of the 20% and 30% lipid emulsions compared with the 10% lipid emulsion.8 The 30% lipid emulsion is only approved by the FDA for infusion in a total nutrient admixture (TNA) and should not be infused directly into patients.
Lipid particles are hydrolyzed in the bloodstream by the enzyme lipoprotein lipase to release free fatty acids and glycerol. Free fatty acids are taken up into adipose tissue for storage (triglycerides), oxidized to energy in various tissues (e.g., skeletal muscle), or recycled in the liver to make lipoproteins. The typical daily dose of IV lipid emulsions in adults is 0.5 to 1 g/kg/day. The maximum dose of IV lipid emulsions in adults is 2.5 g/kg/day6 or 60% of total daily calories, although doses this high are used rarely in practice.
The essential fatty acids in humans are linoleic acid (C18:2 n-6) and α-linolenic acid (C18:3 n-3). Arachidonic acid (C20:4 n-6) is also essential but can be synthesized in vivo from linoleic acid. Adult patients should be provided a minimum of 2% to 4% of total daily calories as linoleic acid and 0.25% to 0.5% of total daily calories as α-linolenic acid to prevent essential fatty acid deficiency.6 This can be achieved practically by providing a minimum of approximately 500 mL of 20% IV lipid emulsion once weekly (or 250 mL twice weekly, on separate days) for most adult patients. Biochemical evidence of essential fatty acid deficiency (e.g., decreased serum linoleic acid, α-linolenic acid, and arachidonic acid concentrations, elevated mead acid concentrations and elevated triene-to-tetraene ratio) can develop in about 2 to 4 weeks in adult patients receiving lipid-free PN. Clinical manifestations (e.g., dry skin, skin desquamation, hair loss, hepatomegaly, anemia, thrombocytopenia, poor wound healing) generally appear after an additional 1 to 2 weeks, although skin changes may take longer to appear.9
Complications and safety concerns related to the administration of IV lipid emulsions include severe hypertriglyceridemia, systemic infection, anaphylactic reactions, and infusion-related reactions. Patients with hypertriglyceridemia, acute kidney injury, chronic kidney disease, and severe metabolic stress may have reduced lipid clearance and are at high risk of developing hypertriglyceridemia. Patients with hepatic dysfunction or pancreatitis (in particular if pancreatitis is caused by hypertriglyceridemia) can also have reduced lipid clearance. IV lipid emulsions should be withheld in adult patients with a serum triglyceride concentration exceeding 400 mg/dL (4.52 mmol/L).
Patients without malnutrition who receive PN may have a higher incidence of infectious complications than patients who do not receive PN.10 IV lipid emulsions support the growth of common bacterial and fungal pathogens, but bacterial growth is slower in TNAs than in IV lipid emulsions alone.11,12 This is due to the acidic pH of amino acid solutions and high osmolarity of PN formulations. The Centers for Disease Control and Prevention (CDC) recommends that infusion of IV lipid emulsions separately from PN (i.e., 2-in-1) be completed within 12 hours of initiation (e.g., two lipid containers can be used, with each container infused over 12 hours). If fluid or volume considerations prohibit a reduced infusion time, the lipid infusion can then be completed within 24 hours. Because TNAs support microbial growth at a slower rate than IV lipid emulsions, the CDC recommends that TNA infusion be completed within 24 hours of initiation. Furthermore, a 0.22-micron bacterial retention filter cannot be used on the infusion line because the average size of lipid particles is approximately 0.4 to 0.5 micron. Strict aseptic techniques must be used when handling IV lipid emulsions to minimize the risk of PN contamination and possible infectious complications.
Patients with allergy to eggs or legumes (e.g., soybeans, broad beans, and lentils) may develop allergic reactions with IV lipid emulsions. Rarely, infusion-related adverse effects including fever, chills, headache, palpitations, dyspnea, chest tightness, and nausea also may occur with rapid infusion of IV lipid emulsions. Extending the IV lipid infusion time (e.g., over 12–24 hours) can minimize infusion-related adverse events and improves lipid clearance. Infusion rate of IV lipid emulsions should not exceed 0.12 g/kg/h.6
Fluid
PN should not be used to treat acute fluid abnormalities. Rather, PN should be adjusted to provide maintenance fluid requirements and to minimize worsening of underlying fluid disturbances, taking into account other fluids the patient is receiving. Daily maintenance fluid requirements for adults can be estimated with the following equation:
Total daily maintenance fluid requirements = 1,500 mL + (20 mL/kg × [wt (kg)–20])*
For patients with fluid deficits, it is safer, clinically indicated, and more cost-effective to correct fluid abnormalities using standard IV fluids (e.g., sodium chloride 0.9% in water, dextrose 5% in water, dextrose 5% and sodium chloride 0.45% in water, or lactated Ringer’s solution). Minimizing fluid volume in PN may be indicated in patients with fluid overload and patients who receive large volumes of fluids from multiple IV medications and fluids (e.g., critically ill, bone marrow transplant), patients with oliguric (urine output less than 400 mL/day) or anuric (urine output less than 50 mL/day) acute kidney injury, and those with congestive heart failure. It is reasonable to provide total daily fluid requirements (both maintenance requirements and GI/other abnormal losses) in the PN admixture in patients who depend on long-term PN. However, caution should be exercised when the PN solution is diluted to an extent that may alter the stability and compatibility of a concentrated solution. Diluting a PN admixture may affect its physical and chemical properties (e.g., the pH, which could affect lipid emulsion stability and calcium–phosphate compatibility); therefore, stability and compatibility data should be confirmed first.
Electrolytes
Electrolytes are essential for many metabolic and homeostatic functions, including enzymatic and biochemical reactions, maintenance of cell membrane structure and function, neurotransmission, hormone function, muscle contraction, cardiovascular function, bone composition, and fluid homeostasis. The causes of electrolyte abnormalities in patients receiving PN may be multifactorial, including altered absorption and distribution; excessive or inadequate intake; altered hormonal, neurologic, and homeostatic mechanisms; altered excretion via GI and renal losses; changes in fluid status and fluid shifts; and medications. PN should not be used to treat acute electrolyte abnormalities, but electrolytes in PN should be adjusted to meet maintenance requirements and to minimize worsening of underlying electrolyte disturbances.
Electrolytes that are included routinely in PN admixtures include sodium, potassium, phosphorus (as phosphate), calcium, magnesium, chloride, and acetate. When determining electrolytes in PN admixtures, the patient’s kidney function always must be taken into account. Typical daily electrolyte maintenance requirements for adults with normal kidney function are listed in Table 100–3.
* For elderly patients (e.g., greater than 60 years old), use 15 mL/kg for every kilogram above 20 kg.
Table 100–3 Approximate Daily Maintenance Electrolyte Requirements for Adults
Sodium
Sodium is the most abundant extracellular cation in the body and is the major osmotically active ion in the extracellular fluid. Sodium concentration determines the distribution of water in the extracellular space, and sodium disorders can be caused by many factors. Patients with abnormal GI losses (e.g., gastric, diarrhea, ostomy, and fistula losses) have increased sodium requirements. Patients with fluid overload and hypervolemic hypotonic hyponatremia may require sodium and fluid restriction. Sodium in PN can be provided in the forms of chloride, acetate, and phosphate salts. One millimole (mmol) of sodium phosphate provides 1.33 mEq of elemental sodium. Total sodium concentration in PN should not exceed 154 mEq/L (154 mmol/L, the equivalent of normal saline).
Potassium
Potassium is the second most abundant cation in the body and is found primarily in the intracellular fluid. Potassium has many important physiologic functions, including regulation of cell membrane electrical action potential (especially in the myocardium), muscular function, cellular metabolism, and glycogen and protein synthesis. Potassium in PN can be provided as chloride, acetate, and phosphate salts. One millimole of potassium phosphate provides 1.47 mEq of elemental potassium. Generally, the concentration of potassium in peripheral PN (PPN) admixtures should not exceed 80 mEq/L (80 mmol/L). While it is safer to limit potassium solution concentration to 80 mEq/L (80 mmol/L) for infusion through a central vein, the maximum recommended potassium concentration for infusion via a central vein is 150 mEq/L (150 mmol/L).13 Patients with abnormal potassium losses (e.g., loop or thiazide diuretic therapy, diarrhea, high gastric fluid output) may have higher potassium requirements, and patients with high gastric fluid output, acute kidney injury or chronic kidney disease may require potassium restriction.
Calcium and Phosphorus
Calcium and phosphorus are essential electrolytes for many physiologic processes and biochemical reactions. Phosphorus is provided as sodium or potassium phosphate in PN. Approximately 10 to 15 mmol of phosphate are needed per 1,000 kilocalories to maintain normal serum phosphorus concentrations (provided the patient is well nourished and has normal kidney function).14 Patients with decreased kidney function may require phosphorus restriction.
The FDA published a safety alert in 1994 in response to two deaths associated with calcium–phosphate precipitation in PN.15 Autopsy reports from these patients revealed diffuse microvascular pulmonary emboli containing calcium–phosphate precipitates. Because calcium and phosphate can bind and precipitate in solution, caution must be exercised when mixing these two electrolytes in PN admixtures. Several factors can affect calcium–phosphate solubility, including the following:
• pH. Largely affected by the final amino acid concentration, to a lesser extent by the dextrose concentration (unless the final amino acid concentration is very low); the lower the solution pH, the less chance there is for calcium–phosphate precipitation; monobasic phosphates predominate at low pH, leaving fewer free dibasic phosphates for precipitation with divalent calcium; monobasic calcium phosphate is more soluble than dibasic calcium phosphate.
• Amino acid concentration. Primary factor that affects pH of the PN admixture; the pH of amino acid stock solutions may vary between commercial products and thus differently affects the final pH of PN admixture; however, in general the higher the final amino acid concentration, the lower the pH of the final admixture (see above), and more phosphates likely bind with amino acids leaving fewer phosphates available to bind with calcium.
• Calcium salt. Calcium gluconate is the preferred calcium salt in PN because it is has a low dissociation constant in solution with lesser free calcium available at a given time to bind phosphate (as opposed to calcium chloride, which dissociates rapidly in solution). One gram of calcium gluconate provides 4.5 mEq of elemental calcium.
• Time. The longer calcium and phosphate are in solution, the more calcium and phosphate will dissociate overtime and increase the risk for calcium–phosphate precipitation.
• Temperature. As temperature increases, more calcium and phosphate dissociate and increase the risk of calcium–phosphate precipitation.
• Order of mixing. Calcium and phosphate should be separated when mixing PN admixtures (e.g., add phosphate first, then all other PN components, and then add calcium last); if calcium is added before all other components are in the PN admixture, including lipid emulsion, then the volume in the PN admixture at the time calcium is added must be used to determine the maximum calcium that can be added.
Magnesium
Magnesium is the second most abundant intracellular cation after potassium. Magnesium serves as an essential cofactor for numerous enzymes and in many biochemical reactions, including reactions involving adenosine triphosphate (ATP).16 Magnesium disorders are multifactorial and can be related to kidney function, disease state(s), and medication therapy. Magnesium in PN typically is provided as magnesium sulfate. One gram of magnesium sulfate provides 8.1 mEq of elemental magnesium.
Chloride and Acetate
Concentration limits for chloride and acetate in PN typically are linked to limitations of sodium and potassium. The usual ratio of chloride:acetate in PN is about 1:1 to 1.5:1. Chloride and acetate primarily play a role in acid–base balance. Chloride is primarily eliminated via the kidneys. Serum chloride concentrations that exceed 130 mEq/L (130 mmol/L) may cause hyperchloremic acidosis. Acetate is converted to bicarbonate at a 1:1 molar ratio. This conversion appears to occur mostly outside the liver. Acetate conversion to bicarbonate is rapid but not immediate, and thus acetate salts should not be used to correct acute severe acidosis. Bicarbonate never should be added to or coinfused with PN solutions. This can lead to the release of carbon dioxide and potentially result in the formation of calcium or magnesium carbonate (very insoluble salts).
Vitamins
The water-soluble and fat-soluble vitamins in the parenteral multivitamin mix are essential cofactors for numerous biochemical reactions and metabolic processes. Parenteral multivitamins are added daily to the PN admixture. Patients with chronic kidney disease may be at risk for vitamin A accumulation and potential toxicity. Serum vitamin A concentrations should be measured in patients with chronic kidney disease when vitamin A accumulation is a concern. Previously, vitamin K was administered either daily or once weekly because IV multivitamin formulations did not contain vitamin K. However, manufacturers have reformulated their parenteral multivitamin products to provide 150 mcg of vitamin K in accordance with FDA recommendations. There is a parenteral adult multivitamin formulation available without vitamin K (e.g., for patients who require warfarin therapy), but standard compounding of PN formulations should include a parenteral multivitamin that contains vitamin K unless otherwise clinically indicated. Water-soluble vitamins, with the exception of vitamin B12, are generally readily excreted and not stored in the body in significant amounts. Deficiencies of water-soluble vitamins can occur rapidly in the absence of adequate vitamin supplementation in PN. For example, refractory severe lactic acidosis and deaths were reported in patients who were receiving PN without added thiamine. Thiamine is a cofactor of the pyruvate dehydrogenase enzyme that is involved in the aerobic metabolism of pyruvate to acetyl-CoA (via the tricarboxylic acid cycle). Deficiency of thiamine pyrophosphate prevents the formation of acetyl-CoA from pyruvate, which is instead converted to lactate via anaerobic metabolism, resulting in lactic acidosis.
Trace Elements
Trace elements are essential cofactors for numerous biochemical processes. Trace elements that are added routinely to PN include zinc, selenium, copper, manganese, and chromium. There are various commercial parenteral trace-element formulations that can be added to PN admixtures (e.g., MTE-5). Zinc is important for wound healing, and patients with high-output fistulas, diarrhea, burns, and large open wounds may require additional zinc supplementation. Patients may lose as much as 12 to 17 mg zinc per liter of GI output (e.g., from diarrhea or enterocutaneous fistula losses); however, 12 mg/day may be adequate to maintain these patients in positive zinc balance.17Patients with chronic severe diarrhea, malabsorption, and short-gut syndrome may also have increased selenium losses and may require additional selenium supplementation. Chromium is a cofactor for glucose metabolism, and patients with chromium deficiency may exhibit glucose intolerance; however, chromium deficiency is a rare cause of hyperglycemia. Patients with cholestasis (serum direct bilirubin concentration that exceeds 2 mg/dL [34.2 µmol/L]) should have manganese and possibly copper restricted to avoid their accumulation and possible toxicity, because both elements undergo biliary elimination. Manganese-induced neurotoxicity has been reported in PN patients with cholestasis and those receiving chronic PN. However, copper deficiency resulting in anemia, pancytopenia and death has occurred when copper was omitted from the PN of PN-dependent patients. Because copper deficiency has been reported to occur anywhere between 6 weeks and 12 months following copper elimination from PN,18 serum copper concentrations need to be regularly monitored (e.g., every 6 weeks at first and 2–3 months thereafter) when copper is omitted from PN admixtures. Trace element status should be monitored at first periodically (e.g., every 2–3 months) in patients at risk for trace element deficiency or accumulation. Once stable, serum trace element concentrations can be monitored less frequently (e.g., every 6–12 months).
PN Additives
Heparin
Heparin (0.5–1 unit/mL of final PN volume) may be added to PN admixtures for three reasons:
• To maintain catheter patency, although this effect is debated To reduce thrombophlebitis, essentially with PPN infusion
•To enhance lipid particle clearance by acting as a cofactor for the lipoprotein lipase enzyme
The benefits and necessity of adding heparin to PN are unclear, and practices vary between institutions. There are also concerns about the stability and compatibility of IV lipid emulsions with heparin added at concentrations above 1 unit/mL. Heparin should be omitted in patients with active bleeding, thrombocytopenia, heparin-induced thrombocytopenia (HIT), or heparin allergy.
Regular Insulin
Regular insulin may be added to PN admixtures for glycemic control. The dose of insulin depends on the severity of hyperglycemia and daily insulin requirements. Generally, once the patient is receiving PN at goal, about 70% of the total insulin administered over the previous 24 hours as sliding scale or continuous infusion can be added to the next PN admixture. The insulin dose should be adjusted based on frequent capillary blood glucose evaluation. Caution should be used when insulin is added to PN to avoid hypoglycemia. Adding insulin to PN rather than administering as a continuous IV infusion does not provide the flexibility of frequent titration of the insulin dose to the desired target blood glucose concentration. As such, severe uncontrolled hyperglycemia is best treated with a continuous insulin infusion.
Histamine-2-Receptor Antagonists
IV histamine-2-receptor antagonists such as ranitidine, famotidine, and cimetidine are compatible with PN and can be added to the daily PN when indicated (e.g., prevention of stress-related mucosal damage). This provides a continuous acid suppression and reduces nursing time by avoiding intermittent scheduled infusions.
Human Albumin
Human albumin is a colloid used as a plasma volume expander and is not a source of nutrition. Albumin should not be added to the PN admixture and should be administered separately from PN because it may increase microbial growth and infectious risk when mixed in the PN admixture. Further, coinfusion of human albumin at the Y-site injection of IV lipid emulsions and TNAs causes disruption and creaming of the IV lipid emulsion.
Iron Dextran
Iron-deficiency anemia in chronic PN-dependent patients may be due to underlying clinical conditions and the lack of regular iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to its infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with IV lipid emulsions and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN admixtures.
NUTRITION ASSESSMENT AND NUTRITIONAL REQUIREMENTS
The first step before delivering nutrition support therapy is to perform a nutritional assessment and determine nutrient requirements based on the patient’s nutritional status and clinical conditions. Subjective and objective data of dietary intake, functional capacity, anthropometrics, weight changes, GI function, medical history, medication therapy, and laboratory data are collected to determine a patient’s nutritional status, identify patients with malnutrition or at risk for malnutrition, and to identify risk factors that may put a patient at risk for nutrition-related problems.1 A nutrition assessment should include:1,19
• Patient history
• Physical assessment including height, weight, ideal body weight (IBW), body mass index (BMI = weight [kg]/height [m2]), and recent weight loss (intentional or unintentional). BMI relates a person’s body weight to their height and is a vague indicator of total body fat mass in adults. BMI categories do not account for frame size, muscle mass, bone, and water weight. Classifications of weight status in relation to BMI are: underweight less than 18.5 kg/m2; normal 18.5 to 24.9 kg/m2; overweight 25 to 29.9 kg/m2; obese greater than or equal to 30 kg/m2
• Physical examination of the musculoskeletal system (e.g., biceps, triceps, quadriceps, temporalis, deltoid, and interosseus muscles) for loss of muscle mass, and examination of the skin and mucous membranes for abnormalities (e.g., noting dry or flaky skin, bruising, edema, ascites, poorly healing wounds) and loss of subcutaneous fat (e.g., triceps, chest)
• Changes in eating habits and GI function, and associated GI symptoms
• Presence and severity of underlying and concurrent disease(s)
• Serum visceral protein concentrations (e.g., albumin, prealbumin). Hypoalbuminemia at baseline or prior to hospitalization may be indicative of malnutrition, and severe hypoalbuminemia may be associated with poor patient outcome. Serum albumin and prealbumin concentrations are not sensitive and specific markers of nutritional status and protein stores in hospitalized patients under metabolic stress (e.g., postsurgery, organ failure, severe burns, trauma, and sepsis). Albumin and prealbumin are negative acute phase proteins. Their liver synthesis is decreased under stress and they are sensitive to non-nutritional factors including hydration status, and kidney and liver functions. Because prealbumin has a shorter half-life (approximately 2 days) than albumin (approximately 20 days), serum prealbumin concentrations are measured usually once weekly to help evaluate the net anabolism in response to nutrition support therapy.
• Serum concentrations of vitamins, trace elements, and iron as indicated
There are several methods to conducting a nutrition assessment, but one approach that has been validated is the Subjective Global Assessment (SGA).1 Application of the SGA requires gathering the data listed above and assessing these parameters (i.e., weight change, dietary changes, GI symptoms, functional capacity, and physical examination) and then assigning a subjective rating (A = well nourished; B = moderately malnourished or suspected of being malnourished; C = severely malnourished).19
After performing a nutrition assessment, estimate the patient’s daily energy and protein requirements (Table 100–4). Indirect calorimetry involves measuring the volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2) to determine the resting metabolic rate (RMR) or resting energy expenditure (REE) and respiratory quotient (RQ = VCO2/VO2). The REE or RMR is the amount of calories required during 24 hours by the body in a nonactive state, and is approximately 10% higher than the basal energy expenditure (BEE, metabolic activity required to maintain life) as it adjusts for the thermic effect of food and awake state. Because critically ill patients may have variable energy expenditure, indirect calorimetry is a valuable tool in assessing energy expenditure in mechanically ventilated patients with multiple and changing clinical conditions. Indirect calorimetry requires expensive equipment and trained personnel to use, and therefore is not feasible in all institutions. Over 200 equations have been developed to determine energy expenditure (EE) for adults. The Harris-Benedict equations, Penn State equations (for nonobese critically ill patients), and the Mifflin St. Jeor equations (for obese noncritically ill patients) are some of the most widely used. Harris-Benedict equations take into account a patient’s sex, weight, height, and age to determine the BEE. A “stress” or “injury” factor is then applied to estimate the daily total EE (TEE). Daily energy requirements are about 100% to 130% of the RMR with adequate protein intake. Alternatively, EE can be estimated based on EE per body weight (i.e., kilocalories per kilogram). However, dry weight or admission weight should be used, and this estimation may not be appropriate in patients who are obese or in elderly patients. There is debate over the best method to estimate energy requirements for obese patients. Several equations have been developed to estimate EE in obese patients. Although there is no consensus on the weight used to estimate EE in obese patients, it is reasonable to use an adjusted body weight (AdjBW) in obese patients to avoid overfeeding. Adjusted body weight can be calculated with 25% to 50% of the difference between the actual weight and IBW added to the IBW. Using a 25% difference in calculating the adjusted body weight further avoids overfeeding when estimating energy requirements:
Table 100–4 Estimating Daily Energy and Amino Acid Requirements in Adults
AdjBW = IBW + (0.25 × [actual weight − IBW])
Amino acid requirements are based on the patient’s nutritional status, clinical condition(s), and kidney and liver function. There are no evidence-based data on what body weight (actual, ideal, or adjusted) should be used for dosing amino acids in adult patients. It is however suggested to dose amino acids based on actual body weight for normal body sized or malnourished adult patients and based on IBW for obese patients. Amino acids are needed in adequate amounts to facilitate anabolism, restore lean body mass, or promote wound healing while avoiding adverse effects from excessive amino acid loading (e.g., azotemia). Actual body weight is used for amino acid dosing in adult patients with severe malnutrition when their body weight is at or below the IBW.
Hypocaloric nutrition support therapy for obese patients (BMI greater than or equal to 30 kg/m2 or actual weight greater than 150% of IBW) is a promising approach. Hypocaloric feeding involves providing high amounts of proteins (approximately 2 g/kg IBW/day) to support anabolism with lower amounts of total calories (average approximately 11–14 kcal/kg [46–59 kJ/kg] actual weight/day, or approximately 22–25 kcal/kg [92–105 kJ/kg] IBW/day) with primary goals to promote net anabolism and avoid hyperglycemia or exacerbation of metabolic stress in critically ill patients.20 Secondary benefits of hypocaloric feeding could be avoiding fat weight gain or possibly promoting fat weight loss. The role of hypocaloric feeding in patients with acute kidney injury or chronic kidney disease, or in patients with end-stage liver disease and hepatic encephalopathy is unknown. Also, the optimal safe duration of hypocaloric feeding in critically ill obese patients is unknown.
Special Patient Considerations: Ethical and Personal Beliefs
When assessing a patient for PN, attention should be given to patients with special personal dietary choices (e.g., vegetarians, vegans) or religious beliefs (e.g., Jehovah’s Witness). These rare situations may present unique challenges for clinicians. Most nutrients used in PN preparations are usually from synthetic sources (e.g., crystalline amino acids) or vegetable sources (e.g., triglycerides used in IV lipid emulsions), with the only exception usually being egg phospholipids used in IV lipid emulsions. Discuss these issues for patients with specific needs who require PN so that a plan can be developed to provide appropriate nutrition support therapy.
PREPARING THE PN PRESCRIPTION: ADMINISTRATION, COMPOUNDING, AND PHARMACEUTICAL ISSUES
After performing a nutrition assessment and estimating nutritional requirements, determine the optimal route to provide nutrition support therapy (e.g., oral, enteral, or parenteral). If PN is deemed necessary, venous access (i.e., peripheral or central; see below) for PN infusion must be obtained. Finally, formulate a PN prescription, and administer PN according to safety guidelines.
Route of PN Administration: Peripheral versus Central Vein Infusion
PN can be administered via a smaller peripheral vein (e.g., cephalic or basilic vein) or via a larger central vein (e.g., superior vena cava) (see Fig. 100–1). PPN is infused via a peripheral vein and generally is reserved for short-term administration (up to 7 days) when central venous access is not available. PN formulations are hyperosmolar, and PN infusion via a peripheral vein can cause thrombophlebitis. Factors that increase the risk of phlebitis include high solution osmolarity, extreme pH, rapid infusion rate, vein properties, catheter material, and infusion time via the same vein.21 The osmolarity of PPN admixtures should be limited to 900 mOsm/L or less to minimize the risk of phlebitis. The approximate osmolarity of a PN admixture can be calculated from the osmolarity of the individual components:
• Amino acids approximately 10 mOsm/g (or 100 mOsm/1% final concentration in PN)
• Dextrose approximately 5 mOsm/g (or 50 mOsm/1% final concentration in PN)
FIGURE 100–1. Selected vascular anatomy. (Reprinted from Krzywda EA, Andris DA, Edmiston CE, Wallace JR. Parenteral Access Devices. In:Gottschlich MM, ed. The A.S.P.E.N. Nutrition Support Core Curriculum: A Case-Based Approach—The Adult Patient. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition:2007:300–322 with permission from the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). A.S.P.E.N. does not endorse the use of this material in any form other than its entirety.)
• Sodium (chloride, acetate, and phosphate) = 2 mOsm/mEq
• Potassium (chloride, acetate, and phosphate) = 2 mOsm/mEq
• Calcium gluconate = 1.4 mOsm/mEq
• Magnesium sulfate = 1 mOsm/mEq
PPN admixtures should be coinfused with IV lipid emulsion when using the 2-in-1 PN because this may decrease the risk of phlebitis due to the iso-osmolarity and close to neutral pH of IV lipid emulsions (Table 100–2). Infectious and mechanical complications may be lower with PPN compared with central venous PN administration. However, because of the risk of phlebitis and osmolarity limit, PPN admixtures have low macronutrient concentrations and therefore usually require large fluid volumes to meet a patient’s nutritional requirements. Given these limitations, every effort should be made to obtain central venous access and initiate central PN when it is unlikely a patient will tolerate enteral or oral nutrition within approximately 7 days.
Central PN refers to the administration of PN via a large central vein, and the catheter tip must be positioned in the vena cava (see Fig. 100–2). Central PN allows the infusion of a highly concentrated, hyperosmolar nutrient admixture. The typical osmolarity of a central PN admixture is about 1,500 to 2,000 mOsm/L. Central veins have much higher blood flow, and the PN admixture is diluted rapidly on infusion, so phlebitis is usually not a concern. Patients who require PN therapy for longer periods of time (greater than 7 days) should receive central PN. One limitation of central PN is the need for placing a central venous catheter and an x-ray to confirm placement of the catheter tip. A commonly used central catheter for PN infusion is a peripherally inserted central venous catheter (PICC) which is inserted into a peripheral vein but the catheter tip is placed in the superior vena cava (see Fig. 100–3). Central venous catheter placement may be associated with complications, including pneumothorax, arterial injury, air embolus, venous thrombosis, infection, chylothorax, and brachial plexus injury.1,21
FIGURE 100–2. Percutaneous nontunneled catheter. (Reprinted from Krzywda EA, Andris DA, Edmiston CE, Wallace JR. Parenteral Access Devices. In:Gottschlich MM, ed. The A.S.P.E.N. Nutrition Support Core Curriculum: A Case-Based Approach—The Adult Patient. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition:2007:300–322 with permission from the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). A.S.P.E.N. does not endorse the use of this material in any form other than its entirety.)
FIGURE 100–3. Peripherally inserted central venous catheter. (Reprinted from Krzywda EA, Andris DA, Edmiston CE, Wallace JR. Parenteral Access Devices. In: Gottschlich MM, ed. The A.S.P.E.N. Nutrition Support Core Curriculum: A Case-Based Approach—The Adult Patient. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition:2007:300–322 with permission from the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). A.S.P.E.N. does not endorse the use of this material in any form other than its entirety.)
Type of PN Formulation: 3-in-1 versus 2-in-1
PN admixtures can be prepared by mixing all components into one bag, or instead, IV lipid emulsion may be infused separately (via a Y-site infusion or through a separate IV catheter or lumen). When all components are mixed together, this is referred to as a 3-in-1 admixture or a TNA.22 When dextrose, amino acids, and all other PN components are mixed together without IV lipid emulsion, this is referred to as a 2-in-1 PN admixture. With a 2-in-1 PN admixture, IV lipid emulsion can be infused separately on a daily or intermittent basis. When lipid emulsion is mixed in the PN, the TNA becomes an emulsion with its physical and chemical characteristics. There are various advantages and disadvantages to using either 3-in-1 or 2-in-1 PN (Table 100–5).
A primary concern when administering PN is safety. The FDA published a safety alert in 1994 in response to two deaths associated with TNA infusion.15 Autopsy reports from these patients revealed diffuse microvascular pulmonary emboli containing calcium–phosphate precipitates. The FDA provided recommendations for safe infusion of PN admixtures containing calcium and phosphate:
Table 100–5 Advantages and Disadvantages of Using 3-in-1 (TNA) or 2-in-1 PN Admixtures
• A 0.22-micron air-eliminating in-line filter should be used for infusion of nonlipid-containing PN.
• A 1.2-micron in-line filter should be used for the infusion of 3-in-1 PN (i.e., a TNA) because it can remove large and unstable lipid droplets and also particulate matter.23
Another concern is the coinfusion of IV medications with PN admixtures. Many IV medications have limited compatibility with 3-in-1 formulations but may be coinfused with a 2-in-1 formulation.24,25 Some medications can be coinfused at the Y-site, few medications can be mixed directly into the PN admixture or coinfused with IV lipid emulsion, and some cannot be mixed or coinfused with the PN admixture.24,25 Always consult compatibility data before adding a medication to a PN admixture or coinfusing it with PN. Medications that are compatible should be added to PN only if it is reasonable and safe (i.e., based on toxicity profile, pharmacokinetic/pharmacodynamic considerations).
The United States Pharmacopeia, Chapter 797 (USP 797) is a document that provides guidelines and best practices for pharmaceutical compounding of sterile products.26 These guidelines address many aspects of compounded sterile preparations (CSPs), including (but not limited to) appropriate training of personnel; appropriate environments for compounding; appropriate storage, handling and labeling of ingredients and final products; and quality assurance. The purpose of USP 797 is to prevent patient harm from CSPs as a result of contamination (including physical, chemical, and bacterial or fungal pathogens), inappropriate ingredients (variability in strength or quality), or inappropriate preparation, compounding, handling, transportation or storage. CSPs are classified as either low-risk level, medium-risk level, high-risk level, or immediate use. CSPs are also assigned an appropriate beyond-use date (BUD), which is the date or time after which a CSP shall not be stored or transported, and it is determined from the date or time the CSP is compounded. PN admixtures are usually classified as medium-risk products, and they are assigned a BUD of 30 hours at controlled room temperature or 9 days at a cold (refrigerated) temperature. The full details of USP 797 are beyond the scope of this chapter. Pharmacists and other health care professionals involved in the preparation of CSPs should review this document along with institutional policies and procedures regarding CSPs.
Formulating a PN Admixture and Regimen
After completing a full nutrition assessment (e.g., SGA),1,19 determine if PN is indicated (Table 100–1), estimate the patient’s daily fluid, energy, and protein requirements (Table 100–4), and develop a PN prescription.
Initiating PN
Exercise caution when initiating PN to avoid hyperglycemia, and fluid and electrolyte abnormalities. Once the goal daily volume is determined, infuse the PN admixture first over 24 hours. For safety, initiate PN at a lower infusion rate (e.g., approximately 50% of goal for anywhere from approximately 12 to 24 hours) on day 1 with no more than 150 to 200 g of dextrose per day (or a maximum dextrose infusion rate of approximately 2 mg/kg/min). Then increase PN up to goal over the following approximately 12 to 24 hours, provided that glycemic control is maintained and the patient does not experience any significant fluid or electrolyte abnormalities. Monitor electrolytes daily and correct as needed. Patients with severe malnutrition should be advanced to goal more slowly and cautiously, and they should be monitored for refeeding syndrome (see Complications of PN below).
Patient Encounter 2
AA was diagnosed with an intestinal leak at the previous surgical site, diffuse peritonitis, sepsis, mild dehydration, and hypovolemic hypotonic hyponatremia.
Laboratory Data
Na = 130 mEq/L (130 mmol/L), K = 3.4 mEq/L (3.4 mmol/L), Cl = 104 mEq/L (104 mmol/L), HCO3 = 21 mEq/L (21 mmol/L), BUN = 14 mg/dL (5 mmol/L), serum creatinine = 0.6 mg/dL (53 µmol/L), blood glucose = 177 mg/dL (9.8 mmol/L), total Ca = 8.3 mg/dL (2.08 mmol/L)], ionized Ca = 2.34 mEq/L (1.17 mmol/L), Mg = 2.1 mg/dL (0.86 mmol/L), phosphorus = 2.1 mg/dL (0.68 mmol/L), TG = 125 mg/dL (1.41 mmol/L), albumin = 3.1 g/dL (31 g/L), WBC count = 14,400/mm3 (14 × 109/L), hemoglobin = 11.2 mg/dL (112 g/L or 6.9 mmol/L), hematocrit = 42% (0.42), and platelets = 164,000/mm3 (164 × 109/L)
AA was taken to the operating room for an exploratory laparotomy, repair of the intestinal leak, and small bowel resection. Postoperatively, a nasogastric (NG) tube was placed and drained 800 to 1,000 mL/day on postoperative days 1 and 2. The surgeons placed a central venous catheter and wanted to start the patient on central PN given her diagnoses of diffuse peritonitis, intestinal leak, evidence of poor intestinal function (given high NG tube output), and history of recurrent bowel obstructions.
Determine appropriate nutritional goals for AA (energy and protein requirements).
What other patient data should be collected to help formulate a PN prescription?
Patient Encounter 3
The surgical team plans to initiate the PN you recommended for AA.
Develop a plan for a complete and balanced PN prescription for AA (including fluid, total calories, dextrose, amino acids, lipid emulsion, electrolytes, vitamins, trace elements, and any additives) and explain the rationale supporting your formulation plan.
How should this PN admixture be initiated and titrated to goal?
Cycling PN
PN should be administered over 24 hours in most hospitalized patients to minimize glucose, fluid, and electrolyte abnormalities. However, administering PN via a cyclic infusion over less than 24 hours, or cycling PN, may be advantageous in certain patients and situations. Cycling PN typically involves administering the same PN volume to a goal infusion time usually over 12 hours rather than over 24 hours. Taper PN to the goal cycle over 2 to 4 days (e.g., 24 hours, then 18 hours the next day, then 14 hours the next day, and then 12 hours the next day). Titrate the PN infusion rate up over 1 to 2 hours to goal rate to avoid hyperglycemia, and taper down over 1 to 2 hours at the end of the cycle to avoid reactive hypoglycemia. Most home infusion pumps can be programmed to cycle a given PN volume automatically over a given time. However, the pharmacist may have to develop an appropriate PN cycle if the infusion pump cannot be programmed.
Cyclic PN has the following advantages:
• It may help alleviate PN-associated liver cholestasis by avoiding continuous compulsive nutrient overload on the liver.27
• It improves the quality of life of patients receiving home PN by allowing the patient time off from PN to engage in normal daily activities. If nocturnal cyclic PN infusion interferes with patient’s sleep pattern by causing overdiuresis, the PN cycle can be extended over a longer infusion time or PN can be infused during other times of the day that are most convenient to the patient.
Concerns with cycling PN include hyperglycemia with high infusion rates, reactive hypoglycemia, and fluid and electrolyte abnormalities. Depending on potassium amounts in the daily PN admixture, cyclic PN infusion should also take into consideration the potassium infusion rate that should not exceed 10 mEq/h. Reactive hypoglycemia can be minimized by tapering down PN over 1 to 2 hours before disconnecting. Typically, the nadir will occur around 30 to 60 minutes or even a little over an hour after the PN is stopped. Random capillary blood glucose concentrations should be checked 4 hours into the PN cycle (approximately 2 hours after reaching goal rate), 15 to 60 minutes after PN stops, and intermittently during the PN cycle as needed for glycemic control.
Transition to Oral or Enteral Nutrition
The goal is to transition the patient to enteral or oral nutrition and taper off PN as soon as indicated clinically. When initiating enteral or oral nutrition, monitor the patient for glucose, fluid, and electrolyte abnormalities. When oral nutrition intake is inconsistent, perform calorie counts to determine the adequacy of nutrition via the oral route. When the patient is tolerating more than 50% of total estimated daily calorie and protein requirements via the oral or enteral route, wean PN by about 50%. PN can be stopped once the patient is tolerating at least 75% of total daily calorie and protein requirements via the oral or enteral route, assuming that intestinal absorption is maintained.
A.S.P.E.N SAFE PRACTICES OF PN
Because serious and sometimes fatal adverse events have occurred with inappropriate use of PN, the A.S.P.E.N. has published updated safe practice guidelines for PN.6 These practice guidelines provide a tool and reference for health professionals for the safe and efficacious use of PN. The guidelines represent the standards of practice as they relate to PN prescribing, compounding, stability, compatibility, labeling, administration, and quality assurance. Although application of these guidelines is voluntary, pharmacists who handle PN should review these guidelines and apply them as they fit in light of the circumstances of their practice sites and individual patient conditions.
COMPLICATIONS OF PN
PN therapy is associated with significant complications, both with short-and long-term therapy. Many complications are related to overfeeding (Table 100–6) Metabolic complications include hyperglycemia, hypoglycemia, hyperlipidemia, hypercapnia, electrolyte disturbances, refeeding syndrome, and acid–base disturbances. Long-term metabolic complications include liver toxicity, vitamin abnormalities, trace-element abnormalities, and metabolic bone disease. Other complications include infectious and mechanical complications that relate to venous catheters.
Hyperglycemia
Hyperglycemia is one of the most common complications associated with PN therapy. The rate of dextrose oxidation may be reduced in patients with stress and hypermetabolism, patients with diabetes or acute pancreatitis, and patients receiving certain medications (e.g., corticosteroids, vasopressors, octreotide, and tacrolimus).28,29 Uncontrolled hyperglycemia can lead to fluid and electrolyte disturbances, hyperglycemic hyperosmolar nonketotic syndrome, hyper-triglyceridemia, and increased risk of infection.30
Hyperglycemia in critically ill patients may be more a reflection of illness severity than from dextrose infusions, provided that the patient is not being overfed.31 Critical illness is associated with increased endogenous glucose production (due to increased glycogenolysis and gluconeogenesis) and insulin resistance. Therefore, critically ill patients have lower tolerance for dextrose infusion compared nonstressed patients. In patients with hyperglycemia, it is reasonable to initiate PN with a continuous dextrose infusion rate of approximately 2 mg/kg/min until glycemic control is achieved and then advance to goal.4Dextrose infusion rate typically ranges between approximately 3 and 4 mg/kg/min but should not exceed 5 mg/kg/min in the adult stressed patient.1,5 Adjusted body weight should be used in obese patients rather than actual weight to calculate dextrose infusion rate. A portion of calories can be provided with IV lipid emulsion rather than dextrose to help decrease hyperglycemia, provided that the patient does not have hypertriglyceridemia. Overfeeding (with dextrose and with total calories) always must be avoided.
Table 100–6 Consequences of Overfeeding
Hyperglycemia can impair cellular and humoral host defenses and can lead to the development of nosocomial and wound infections.30 Historically, hyperglycemia has been defined as blood glucose concentrations of more than 200 to 220 mg/dL (11.1–12.21 mmol/L), and concentrations of 150 to 200 mg/dL (8.3–11.1 mmol/L) were considered “acceptable” in critically ill patients. Based on early clinical evidence, tight glucose control (e.g., 80–110 mg/dL or 4.4–6.1 mmol/L) with intensive insulin therapy using continuous insulin infusion in surgical critically ill patients reduced infection rates, patient comorbidities, and mortality.32 It also appears that the benefits observed are due to glycemic control rather than to the dose of insulin.33 Achieving a goal serum glucose concentration of 80 to 110 g/dL (4.4–6.1 mmol/L) may be a challenge while avoiding hypoglycemia. A single episode of severe hypo glycemia (blood glucose concentrations less than 40 g/dL or 2.2 mmol/L) could be an independent risk factor for increased patient mortality. Because of the heterogeneity of the critically ill population and the increased hypoglycemia risk with intensive insulin therapy, the exact goal range for optimal glucose control and the effects on hyperglycemia-associated complications in critically ill patients are still debated. However, an upper threshold for serum glucose concentration of 145 mg/dL (8.0 mmol/L) has been suggested as acceptable.34
The clinical benefits of tight glucose control (blood glucose concentrations 80–110 mg/dL [4.4–6 mmol/L]) that were derived from the Van den Berghe study were not replicated in the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation—Survival Using Glucose Algorithm Regulation) study.35 The NICE-SUGAR study was an international, multi-center, prospective, randomized, controlled, unblinded study of 6,104 medical and surgical adult patients admitted to the intensive care units of 42 hospitals. Patients were included in the study if they were expected to be in the intensive care unit for at least 3 days. Patients were randomized to receive intensive insulin therapy to maintain blood glucose concentrations between 81 and 108 mg/dL (4.5–6 mmol/L) or to conventional insulin therapy to keep blood glucose concentrations between 144 and 180 mg/dL (8–10 mmol/L). Blood glucose control was achieved with intravenous insulin infusion. Study results showed a significantly higher 90-day mortality rate (primary outcome) in the intensive glucose control group as compared to the conventional group (27.5% versus 24.9%, respectively; p = 0.02). There was no benefit from intensive glucose control on the secondary and tertiary outcomes including length of intensive care unit stay, days on mechanical ventilation, incidence of bloodstream infections, need for renal replacement therapy, and blood transfusions. A significantly higher incidence of severe hypoglycemia (blood glucose concentrations less than or equal to 40 mg/dL [less than or equal to 2.2 mmol/L]) occurred in 6.8% of patients in the intensive glucose control group as compared to 0.5% in the conventional group (p < 0.001). Although the NICE-SUGAR study results suggest that optimal blood glucose concentrations in critically ill patients are best maintained between 144 and 180 mg/dL (8–10 mmol/L), it is expected that further data analysis may provide a better explanation of the study findings and their applicability to the diverse critical care patient population.
The use of regular insulin as a continuous infusion rather than adding insulin to PN reduces the risk of prolonged hypoglycemia because the insulin drip can be readily titrated as insulin requirements change. In patients with diabetes, IV insulin doses in the PN admixture to maintain euglycemia range approximately from 0.05 to 0.2 unit of insulin per each gram of dextrose in PN. Starting with a low insulin dose and adjusting the dose daily based on capillary blood glucose evaluation is indicated in order to avoid hypoglycemia. Further and careful reduction to the insulin dose should be made as guided by frequent capillary blood glucose monitoring when metabolic stress decreases, acute pancreatitis resolves, or when corticosteroid doses are tapered off or discontinued.
Hypoglycemia
Hypoglycemia can occur in patients when PN is interrupted suddenly (reactive hypoglycemia), especially when patients are treated with insulin or as a result of insulin overdosing in PN.1 It is essential to prevent hypoglycemia and, if it occurs, to identify and treat it promptly. Reactive hypoglycemia typically is rare and usually can be avoided by tapering PN over 1 to 2 hours before discontinuation rather than abruptly stopping the infusion (especially if the patient is receiving insulin in PN or if the patient is not receiving oral or enteral nutrition). Reactive hypoglycemia generally occurs within 15 to 60 minutes after stopping PN (especially in neonatal patients), although it can occur later than this after discontinuing PN.1 Capillary blood glucose concentrations should be monitored about 15 to 60 minutes after stopping PN infusion in order to detect any potential hypoglycemia. If PN is interrupted abruptly (e.g., due to lost IV access), infusing dextrose 10% in water at the same rate as PN should prevent hypoglycemia. In patients with poor venous access, reduce the PN infusion rate by 50% for 1 hour before discontinuing. Another alternative to prevent reactive hypoglycemia is to provide a glucose source via the oral route (by mouth or sublingually) when feasible. Monitor capillary blood glucose concentrations regularly in patients receiving insulin in PN, and adjust insulin doses accordingly.
Hyperlipidemia
Patients receiving IV lipid emulsion may be at risk for hyperlipidemia and hypertriglyceridemia. Hyperglycemia can lead to hypertriglyceridemia and is the most common cause of hypertriglyceridemia in patients receiving PN. Hyperlipidemia in patients receiving PN may lead to a reduction in pulmonary gas diffusion and pulmonary vascular resistance (especially in patients with underlying pulmonary and vascular disease).36 Severe hypertriglyceridemia (especially when serum triglyceride concentrations exceed 1,000 mg/dL or 11.3 mmol/L) can precipitate acute pancreatitis.37 Hypertriglyceridemia may develop as a result of increased fatty acid synthesis due to hyperglycemia or impaired lipid clearance or in patients with history of hyperlipidemia, obesity, diabetes, alcoholism, kidney failure, liver failure, multiorgan failure, sepsis, pancreatitis, or as a result of medications (e.g., propofol, corticosteroids, cyclosporine, and sirolimus).38 Propofol is formulated in a 10% lipid emulsion (which is not cleared as effectively as the 20% or 30% lipid emulsions) and may lead to hyper-triglyceridemia. It also has been proposed that propofol could have direct effects on lipid metabolism, given that hypertriglyceridemia associated with propofol infusion has been observed with lipid doses that are lower than those typically given in PN.38,39
A higher PL:TG ratio in the 10% lipid emulsion has been proposed to cause the appearance of the abnormal lipoprotein X particles (rich in phospholipids [approximately 60%] and cholesterol [approximately 25%], small amounts of triglycerides) in the blood.8,38 Lipoprotein X may compete with lipid particles for metabolism by lipoprotein lipase. Therefore, IV lipid emulsions with a lower PL:TG ratio (i.e., 20% or 30% lipid emulsions) have improved clearance compared with emulsions with a higher PL:TG ratio (i.e., 10% lipid emulsion)8,38 and should preferentially be used, especially in patients with hypertriglyceridemia. Lipid clearance may be improved by newer formulations of mixed medium-and long-chain triglycerides; however, these products are not yet approved for use in the United States.
Monitor serum triglyceride concentrations regularly during PN therapy (e.g., at the initiation of PN, then once or twice per week initially, and thereafter depending on clinical condition). If a patient develops hypertriglyceridemia, identify and correct the underlying cause(s) if possible (e.g., treatment of hyperglycemia or reduction of dextrose and/or lipid dose). Prolonging the infusion of IV lipid emulsion (e.g., over 24 hours) may improve clearance; however, this may require hanging two containers daily because each container of lipid emulsion should infuse for only 12 hours based on USP 797 and infection-control policies and practices. If a patient is receiving propofol, take into account the calories administered from the 10% lipid emulsion in propofol (1.1 kcal/mL or 4.6 kJ/mL). For safety reasons, IV lipid emulsion should be withheld in patients receiving propofol. It also should be held when the serum is lipemic or when serum triglyceride concentrations are greater than 400 mg/dL (4.5 mmol/L). When this occurs, restart IV lipid emulsions when the serum triglyceride concentration is approximately 200 to 400 mg/dL (2.3–4.5 mmol/L) (or less), and administer IV lipids only two to three times per week to prevent essential fatty acid deficiency.
Hypercapnia
Hypercapnia (abnormally high concentration of carbon dioxide in the blood) can develop as a result of overfeeding with both dextrose and total calories.1,40 Excess carbon dioxide production and retention can lead to acute respiratory acidosis. The excess carbon dioxide also will stimulate compensatory mechanisms, resulting in an increase in respiratory rate in order to eliminate the excess carbon dioxide via the lungs. This increase in respiratory workload can cause respiratory insufficiency that may require mechanical ventilation. Reducing total calorie and dextrose intake would result in resolution of hypercapnia if due to overfeeding.
Acid–Base Disturbances
Acid–base disturbances associated with PN usually are related to the patient’s underlying condition(s). However, acid–base abnormalities may develop as a result of changes in chloride or acetate concentrations in PN admixtures. Because acetate is converted to bicarbonate in the body, excessive acetate salts in PN can lead to metabolic alkalosis; excessive chloride salts in PN can lead to metabolic acidosis. PN should not be used to treat or correct acute underlying disorders. However, adjusting chloride or acetate salts in the PN admixture may help to prevent these acid–base disorders or minimize worsening of any underlying acid–base disorders.
Liver Complications
The incidence of liver complications associated with PN ranges from approximately 7% to 84%, and end-stage liver disease develops in as many as 15% to 40% of adult patients on long-term PN.38 Patients often develop a mild increase in liver enzymes within 1 to 2 weeks of initiating PN, but this generally resolves when PN is discontinued. Severe liver complications include hepatic steatosis (fat deposition in liver), steatohepatitis (a severe form of liver disease characterized by hepatic inflammation that may progress rapidly to liver fibrosis and cirrhosis), cholestasis, and cholelithiasis.38
Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients’ PN showed reversal of steatosis.
Cholestasis is a common problem in patients who are dependent on PN. Factors that predispose PN patients to cholestasis include overfeeding, lack of bowel stimulation, bowel rest (decrease in cholecystokinin secretion), long duration of PN, short-bowel syndrome, bacterial overgrowth and translocation, and sepsis.38 Patients may exhibit increased liver transaminases, increase alkaline phosphatase and gamma-glutamyl transferase concentrations, and mainly increased bilirubin concentrations with jaundice. The most sensitive marker of cholestasis is an increased serum conjugated bilirubin concentration of 2 mg/dL (34.2 µmol/L) or more.38 Cholestasis generally is reversible if PN is discontinued before permanent liver damage occurs. Serum liver enzyme concentrations may take up to 3 months to return to normal after discontinuing PN. Steps to prevent cholestasis associated with PN include early initiation of enteral or oral feedings, using a balanced PN formulation, avoiding overfeeding, cyclic PN infusion, and treating and avoiding sepsis.38 Limiting IV lipid emulsion infusion to 1 or 2 times weekly at a dose no less than to prevent essential fatty acid deficiency may also decrease serum bilirubin concentrations and improve cholestasis. Pharmacologic treatments include ursodeoxycholic acid (ursodiol), which may improve bile flow and reduce the signs and symptoms of cholestasis. However, ursodiol is only available in an oral dosage form, and absorption may be limited in patients with intestinal resections. If other measures are not successful, and bacterial overgrowth is thought to be contributing to cholestasis, courses of oral metronidazole, oral gentamicin, or oral neomycin have been used to reduce bacterial overgrowth.
Cholelithiasis can develop as a result of decreased gallbladder contractility, especially in the absence of enteral or oral intake. Lack of intestinal stimulation reduces secretion of cholecystokinin, a peptide hormone secreted in the duodenum that induces gallbladder contractility. The best prevention of cholelithiasis is early initiation of enteral or oral feeding, as stated earlier (to stimulate secretion of cholecystokinin, gallbladder contraction and emptying, and intestinal motility). Pharmacologic treatment with cholecystokinin-octapeptide (sincalide) to stimulate gallbladder contraction and bile flow does not prevent PN-associated cholestasis or improve serum conjugated bilirubin concentrations.
Monitor liver function tests, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, and conjugated bilirubin, at the initiation of PN and regularly thereafter during PN therapy. The frequency of monitoring liver function tests depends on the presence or absence of liver disease. This varies from one to two times weekly in the acute setting to once weekly to once monthly in the stable home PN patient.
Manganese Toxicity
Manganese is a trace element that serves as a coenzyme in multiple biochemical reactions. Manganese usually is supplied in PN admixtures as part of the trace element package in an adult dose of 0.5 mg/day; however, this may be excessive for longer-term PN patients. Manganese accumulation can occur in patients with cholestasis, and the most common toxicity is neurotoxicity, but liver toxicity also may occur.38Neurologic symptoms associated with manganese toxicity include headache, somnolence, weakness, confusion, tremor, muscle rigidity, altered gait, and mask-like face (a Parkinson’s-like syndrome).38Conversely, some patients with hypermanganesemia may not exhibit symptoms of toxicity. Periodic measurement of blood-manganese concentrations in patients on long-term PN is recommended. Patients with cholestasis receiving PN may require restriction of manganese in PN to prevent its accumulation and possible toxicity.
Metabolic Bone Disease
Metabolic bone disease is a condition of bone demineralization leading to osteomalacia, osteopenia, or osteoporosis in patients receiving long-term PN. Metabolic bone disease, to some degree, may occur in as many as 40% to 100% of patients receiving long-term PN.38 Often patients are asymptomatic, although symptoms can include bone pain, back pain, and fractures. Patients often will have increased serum alkaline phosphatase concentrations, low to normal parathyroid hormone (PTH) concentrations, normal 25-hydroxy vitamin D, low 1,25 dihydroxyvitamin D concentrations, hyper-calcemia or hypocalcemia, and hypercalcuria.41 Because patients may be asymptomatic, diagnosis can be incidental. Radiologic techniques commonly used in diagnosing bone disease include quantitative computed tomography (CT) and bone mineral density.41
Factors that can predispose patients to developing metabolic bone disease include deficiencies of phosphorus, calcium, and vitamin D; vitamin D and/or aluminum toxicity; amino acids and hyperosmolar dextrose infusions; chronic metabolic acidosis; corticosteroid therapy; and lack of mobility.38,41 Calcium deficiency (due to decreased intake or increased urinary excretion) is one of the major causes of metabolic bone disease in patients receiving PN. Provide adequate calcium and phosphate with PN to improve bone mineralization and help to prevent metabolic bone disease. Administration of amino acids and chronic metabolic acidosis also appear to play an important role. Provide adequate amounts of acetate in PN admixtures to maintain acid–base balance.
Vitamin D toxicity has been suggested as a cause of metabolic bone disease. However, vitamin D deficiency results in bone loss, and data on vitamin D excess and metabolic bone disease remain controversial.
Aluminum toxicity appears to play a role in the development of metabolic bone disease in patients on long-term PN, possibly by impairing calcium bone fixation,42 inhibiting the conversion of 25-hydroxyvitamin D to the active 1,25-dihydroxyvitamin D, and/or reducing PTH secretion.38,43 The FDA has been investigating the issue of aluminum contamination in parenteral products and issued a rule specifying acceptable aluminum concentrations in large-volume parenterals in the year 2000.44 The rule further stated that the package insert (“Precautions”) for large-volume parenterals used in making PN should indicate that the product contains no more than 25 mcg/L of aluminum and defined a safe upper limit for parenteral aluminum intake at less than 4 to 5 mcg/kg/day. This has required a great amount of effort by manufacturers to meet these limits and requires pharmacy policies for monitoring aluminum concentrations in PN admixtures. Pharmacies should use products with the lowest labeled aluminum content for the making of PN. Patients who are chronically dependent on PN should have their serum aluminum concentrations routinely monitored or whenever metabolic bone disease is suspected or diagnosed.
Encourage patients on long-term PN to engage in regular low-intensity exercise. Yearly bone density measurements also should be performed on patients on long-term PN and when metabolic bone disease is suspected.
Refeeding Syndrome
Refeeding syndrome describes the metabolic derangements that occur during nutritional repletion of patients who are starved, underweight, or severely malnourished.45 Hypophosphatemia and associated complications are the classic signs and symptoms, but refeeding syndrome encompasses a constellation of fluid and electrolyte abnormalities affecting multiple organ systems, including neurologic, cardiac, hematological, neuromuscular, and pulmonary function. The most severe cases of refeeding syndrome have resulted in cardiac failure, seizures, coma, and death.45 The reintroduction of carbohydrates/glucose drives metabolism back to using glucose as the predominant fuel source. This increases insulin secretion, creates a high demand for the production of phosphorylated intermediates of glycolysis (e.g., ATP, and 2,3-diphosphoglycerate [2,3-DPG]), inhibits fat metabolism, and causes an intracellular shift of phosphorus, potassium, and magnesium. These changes, in combination with pre-existing low total body stores of phosphorus, potassium, and magnesium and enhanced cellular uptake of phosphorus during anabolic refeeding, result in hypophosphatemia, hypokalemia, and hypomagnesemia. Vitamin deficiencies (e.g., thiamine) also may exist or be precipitated during refeeding. High carbohydrate intake increases the demand for thiamine, an essential cofactor involved in carbohydrate metabolism. This can precipitate thiamine deficiency with its potential complications, including lactic acidosis and neurologic abnormalities,45,46 as well as myocardial dysfunction and congestive heart failure. Other metabolic alterations that may occur include expansion of the extracellular water compartment, fluid imbalance, and fluid intolerance.
The primary goal is preventing refeeding syndrome when initiating PN in high-risk patients (e.g., patients with prolonged lack of adequate nutritional intake, significant weight loss, or moderate-severe malnutrition). When initiating nutrition support, the rule of thumb to prevent refeeding syndrome is to “start low and go slow.” Initiate PN cautiously (e.g., approximately 25% of estimated nutritional requirements on day 1), and gradually increase to goal over 3 to 5 days. Correct electrolyte abnormalities (e.g., hypophosphatemia, hypokalemia, and hypomagnesemia) before initiating PN, and provide supplemental phosphate, potassium, and magnesium in or outside of PN (if the patient has normal kidney function). Well-nourished patients require 10 to 15 mmol of phosphate per 1,000 kcal to avoid hypophosphatemia,14 but patients with moderate to severe malnutrition who are at risk for refeeding syndrome will require more aggressive supplementation. Doses of IV phosphate as high as 0.64 to 1 mmol/kg have been used to treat severe hypophosphatemia (provided the patient has normal kidney function).47,48 Vitamin supplementation also should be provided in addition to the multivitamin provided in PN. Provide supplemental oral or IV thiamine 100 mg/day and folic acid 1 mg/day for about a week. In addition, minimize fluid and sodium intake during the first few days of PN (e.g., total fluid of 1,000 mL/day or less and sodium of 20 mEq/day or less).49 Assess patients for fluid balance, signs of edema, fluid overload, and weight gain because any gain of more than 1 kg/week likely represents fluid retention.49 Monitor patients closely for signs and symptoms of refeeding syndrome. Monitor vital signs (i.e., heart rate, blood pressure, and respiratory rate), mental status, and neurologic and neuromuscular function routinely during the first several days of PN until goal is reached. Monitor pulse oximetry and any electrocardiographic changes when indicated clinically.
Infectious Complications
Patients receiving central PN are at increased risk of developing infectious complications caused by bacterial and fungal pathogens.1,50 Infections may be related to placement of a central venous catheter, contamination of a central venous catheter or IV site (catheter-related infection), and persistent hyperglycemia. Strict aseptic techniques must be used when placing the catheter, along with continuous care of the catheter and infusion site. Catheter-related bloodstream infections are a common complication in long-term PN patients, often requiring hospital admission for parenteral antimicrobial therapy and/or removal of the catheter. Contamination of the PN admixture is possible, although rare if protocols are followed for aseptic preparation of PN admixtures. Lack of use of the intestinal tract also may increase the risk of infection possibly by reducing gut immunity, leading to intestinal bacterial overgrowth and subsequent systemic bacterial translocation.
Mechanical Complications
Mechanical complications of PN are related to venous catheter placement and the system and equipment used to administer PN. A central venous catheter must be placed by a trained professional, and risks associated with placement include pneumothorax, arterial puncture, bleeding, hematoma formation, venous thrombosis, and air embolism.1,21 Over time, the venous catheter may require replacement. Problems with the equipment include malfunctions of the infusion pump, IV tubing sets, and filters.
MONITORING PN THERAPY
When initiating PN, patients should have important baseline laboratory values checked to assess electrolyte status, organ function, and nutritional status (Table 100–7). Baseline laboratory monitoring should include:
• Basic metabolic panel (i.e., serum sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, and calcium), serum phosphorus and magnesium.
• Liver function, including AST, ALT, alkaline phosphatase, lactate dehydrogenase (LDH), total and conjugated bilirubin; a comprehensive metabolic panel can be ordered (i.e., serum sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, AST, ALT, alkaline phosphatase, albumin, and total bilirubin), but phosphorus, magnesium, and fractionated or conjugated bilirubin are not included on this panel and must be ordered separately.
• Serum albumin, prealbumin, and triglycerides.
• Complete blood count (including hemoglobin, hematocrit, red blood cell count, and white blood cell count), and platelets with differential.
Thereafter, the preceding parameters and other nutritional parameters should be monitored routinely or as indicated (Table 100–7). Random capillary blood glucose concentrations also should be monitored every 6 to 8 hours when initiating PN, and regular insulin should be administered to control blood glucose concentrations as needed.
Patient Encounter 4
The surgical team plans to initiate PN for AA as you have recommended. Propofol was initiated and the rate titrated for AA adequate sedation. Laboratory data were listed previously.
What other laboratory data or monitoring parameters should be obtained before initiating PN?
How frequently should you monitor each of the various parameters after initiating PN?
What potential complications of PN should you monitor for in AA?
What approaches should be undertaken to prevent and treat hyperglycemia in AA?
How should the PN formulation be adjusted following propofol initiation in AA?
Table 100–7 Suggested Frequency of Monitoring Parameters in Hospitalized Patients Receiving PN
SUMMARY AND CONCLUSION
PN is an effective and potentially lifesaving method of administering nutrition support therapy in patients who cannot receive adequate oral or enteral nutrition, but may be associated with several complications. Enteral nutrition is the preferred route of providing nutrition support therapy. Administration of PN is associated with significant adverse effects, and patients must be monitored closely. Patients receiving PN therapy are at risk for metabolic, infectious, and mechanical complications. Optimal design of a PN regimen is essential to minimize the risk of adverse effects and complications, and patients must be monitored closely while receiving PN in order to optimize outcomes.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
REFERENCES
1. American Society for Parenteral and Enteral Nutrition Board of Directors and the Clinical Guidelines Task Force. Guidelines for the use of parenteral and enteral nutrition in adult and pediatric patients. JPEN J Parenter Enteral Nutr 2002;26:1SA–138SA.
2. McClave SA, Martindale RG, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) J PEN J Parenter Enteral Nutr 2009;33:277–316.
3. Woodcock NP, Zeigler D, Palmer MD, et al. Enteral versus parenteral nutrition: A pragmatic study. Nutrition 2001;17:1–12.
4. Wolfe RR, Allsop JR, Burke JF. Glucose metabolism in man: Responses to intravenous glucose infusion. Metabolism 1979;28:210–220.
5. Rosmarin DK, Wardlaw GM, Mirtallo J. Hyperglycemia associated with high, continuous infusion rates of total parenteral nutrition dextrose. Nutr Clin Pract 1996;11:151–156.
6. The American Society for Parenteral and Enteral Nutrition. Task force for the revision of safe practices for parenteral nutrition. Safe practices of parenteral nutrition. JPEN J Parenter Enteral Nutr 2004;28:S39–S70.
7. Driscoll DF, Bhargava HN, Li L, et al. Physicochemical stability of total nutrient admixtures. Am J Health Syst Pharm 1995;52:623–634.
8. Ferezou J, Bach AC. Structure and metabolic fate of triacylglycerol-and phospholipid-rich particles of commercial parenteral fat emulsions. Nutrition 1999;15:44–50.
9. Goodgame JT, Lowry SF, Brennan MF. Essential fatty acid deficiency in total parenteral nutrition: Time course of development and suggestions for therapy. Surgery 1978;84:271–277.
10. The Veteran Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325:525–532.
11. Crocker KS, Noga R, Filibeck DJ, et al. Microbial growth comparisons of five commercial parenteral lipid emulsions. JPEN J Parenter Enteral Nutr 1984;8:391–395.
12. D’Angio R, Quercia RA, Treiber NK, et al. The growth of microorganisms in total parenteral nutrition admixtures. JPEN J Parenter Enteral Nutr 1987;11:394–397.
13. Lacy CH, Armstrong LL, Goldman MP, et al., eds. Drug Information Handbook, 14th ed. Hudson, OH: Lexi-Comp, 2006:1292–1294.
14. Sheldon GF, Grzyb S. Phosphate depletion and repletion: Relation to parenteral nutrition and oxygen transport. Ann Surg 1975;182:683–689.
15. Food and Drug Administration. Safety alert: Hazards of precipitation associated with parenteral nutrition. Am J Hosp Pharm 1994;51:1427-1428.
16. Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med 2005;20:3–17.
17. Wolman S, Anderson GH, Marliss EB, Jeejeebhoy YN. Zinc in total parenteral nutrition: Requirements and metabolic effects. Gastroenterology 1979;76:458–467.
18. Spiegel JE, Willenbucher RF. Rapid development of severe copper deficiency in a patient with Crohn’s disease receiving parenteral nutrition. JPEN J Parenter Enteral Nutr 1999;23:169–172.
19. Pesce-Hammond K, Wessel J. Nutrition assessment and decision making. In: Merritt R, ed. The A.S.P.E.N. Nutrition Support Practice Manual, 2nd ed. Silver Spring, MD: American Society for Parenteral and Enteral Nutrition, 2005:3–26.
20. Dickerson RN. Specialized nutrition support in the hospitalized obese patient. Nutr Clin Pract 2004;19:245–254.
21. Bodoky A. Parenteral nutrition by peripheral vein, portal vein, or central venous catheter? World J Surg 1986;10:47–52.
22. Driscoll DF. Total nutrient admixtures: Theory and practice. Nutr Clin Pract 1995;10:114–119.
23. Driscoll DF, Bacon MN, Bistrian BR. Effects of in-line filtration on lipid particle size distribution in total nutrient admixtures. JPEN J Parenter Enteral Nutr 1996;20:296–301.
24. Trissel LA, Gilbert DL, Martinez JF, et al. Compatibility of parenteral nutrient solutions with selected drugs during simulated Y-site administration. Am J Health Syst Pharm 1997;54:1295–1300.
25. Trissel LA, Gilbert DL, Martinez JF, et al. Compatibility of medications with 3-in-1 parenteral nutrition admixtures. JPEN J Parenter Enteral Nutr 1999;23:67–74..
26. (797) Pharmaceutical compounding—Sterile preparations. United States Pharmacopeial Convention, Revision Bulletin 2008;1–61..
27. Huang TL, Lue MC, Chen LL. Early use of cyclic TPN prevents further deterioration of liver functions for the TPN patients with impaired liver function. Hepatogastroenterology 2000;47:1347–1350.
28. Watters JM, Norris SB, Kirkpatrick SM. Endogenous glucose production following injury increases with age. J Clin Endocrinol Metab 1997;82:3005–3010.
29. Campbell IT. Limitations of nutrient intake. The effect of stressors: Trauma, sepsis and multiple organ failure. Eur J Clin Nutr 1999;53(Suppl 1):S143–S147.
30. Butler SO, Btaiche IF, Alaniz C. Relationship between hyperglycemia and infection in critically ill patients. Pharmacotherapy 2005;25:963–976.
31. Bjerke HS, Shabot MM. Glucose intolerance in critically ill surgical patients: Relationship to total parenteral nutrition and severity of illness. Am Surg 1992;58:728–731.
32. Van Den Berghe G, Wouters PJ, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359–1367.
33. Van Den Berghe G, Wouters PJ, Bouillon R, et al. Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control. Crit Care Med 2003;31:359–366.
34. Finney SJ, Zekveld C, Elia A, et al. Glucose control and mortality in critically ill patients. JAMA 2003;290:2041–2047.
35. The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283–1297.
36. Greene HL, Hazlett D, Demaree R. Relationship between Intralipid-induced hyperlipemia and pulmonary function. Am J Clin Nutr 1976;29:127–135.
37. Grundy SM, Billheimer D, Chait A, et al. Summary of the second report of the national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA 1993;269:3015–3023.
38. Btaiche IF, Khalidi N. Metabolic complications of parenteral nutrition in adults, part 1 and part 2. Am J Health Syst Pharm 2004;61:1938–1949, 2050–2059.
39. Devlin JW, Lau AK, Tanios MA. Propofol-associated hypertriglyceridemia and pancreatitis in the intensive care unit: An analysis of frequency and risk factors. Pharmacotherapy 2005;25:1348–1352.
40. Liposky JM, Nelson LD. Ventilatory response to high caloric loads in critically ill patients. Crit Care Med 1994;22:796–802.
41. Buchman AL, Moukarzel A. Metabolic bone disease associated with total parenteral nutrition. Clin Nutr 2000;19:217–231.
42. Vargas JH, Klein GL, Ament ME, et al. Metabolic bone disease of total parenteral nutrition: Course after changing from casein to amino acids in parenteral solutions with reduced aluminum content. Am J Clin Nutr 1988;48:1070–1078.
43. Klein GL. Metabolic bone disease of total parenteral nutrition. Nutrition 1998;14:149–152.
44. Department of Health and Human Services, Food and Drug Administration. Aluminum in large and small volume parenterals used in total parenteral nutrition. Fed Regist 2000(Docket No. 90N-0056);65:4103–4111.
45. Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding syndrome. Nutr Clin Pract 2005;20:625–633.
46. Romanski SA, McMahon M, Molly M. Metabolic acidosis and thiamine deficiency. Mayo Clin Proc 1999;74:259–263.
47. Clark CL, Sacks GS, Dickerson RN, et al. Treatment of hypophosphatemia in patients receiving specialized nutrition support using a graduated dosing scheme: Results from a prospective clinical trial. Crit Care Med 1995;23:1504–1511.
48. Brown KA, Dickerson RN, Morgan LM, et al. A new graduated dosing regimen for phosphorus replacement in patients receiving nutrition support. JPEN J Parenter Enteral Nutr 2006;30:209–214.
49. Apovian CM, McMahon MM, Bistran BR. Guidelines for refeeding the marasmic patient. Crit Care Med 1990;18:1030–1033.
50. Beghetto MG, Victorino J, Teixeira L, de Azevedo MJ. Parenteral nutrition as a risk factor for central venous catheter-related infection. JPEN J Parenter Enteral Nutr 2005;29:367–373.