Parenteral nutrition should be considered if energy intake cannot, or it is anticipated that it cannot, be met by enteral nutrition (<50% of daily requirements) for more than 7–10 days. This guideline originates from two intensive care unit (ICU)-focused meta-analyses citing increased complications and increased overall mortality in ICU patients receiving early parenteral nutrition (i.e., within 7 days of admission), compared with those receiving no nutrition support.1,2 Recent studies have found that critically ill patients who are unable to meet caloric goals by enteral nutrition alone for the first 8 days of hospitalization have longer durations of stay and greater mortality rates than those in whom total parenteral nutrition (TPN) is withheld for the first 8 days after admission.2
Central Parenteral Nutrition
- The infusion of hyperosmolar (usually >1500 mOsm/L) nutrient solutions requires a large-bore, high-flow vessel to minimize vessel irritation and damage.
- Percutaneous subclavian vein catheterization and peripherally inserted central venous catheterization (PICC) are the most common techniques for central parenteral nutrition (CPN) access. The internal jugular, saphenous, and femoral veins are also used, although they are less desirable due to patient discomfort and difficulty in maintaining sterility. Tunneled catheters are preferred in patients likely to receive >8 weeks of TPN in order to decrease the risk of mechanical failure.
- PICCs are increasingly used to provide CPN in patients with adequate antecubital vein access. They should not be used in patients requiring CPN for an extended time (>6 months).
CPN Macronutrient Solutions
- Crystalline amino acid solutions consisting of 40%–50% essential and 50%–60% nonessential amino acids (usually with little or no glutamine, glutamate, aspartate, asparagine, tyrosine, and cysteine) are used to provide protein needs (Table 2-2). Infused amino acids are oxidized and should be included in the estimate of energy provided as part of the parenteral formulation.
- Some amino acid solutions have been modified for specific disease states such as those enriched in branched-chain amino acids for use in patients with hepatic encephalopathy and those that contain mostly essential amino acids for use in patients with renal insufficiency.
- Glucose (dextrose) in IV solutions is hydrated; each gram of dextrose monohydrate provides 3.4 kcal. Although there is no absolute requirement for glucose in most patients, providing >150 g of glucose per day maximizes protein balance.
- Lipid emulsions are available as a 10% (1.1 kcal/mL) or 20% (2.0 kcal/mL) solution and provide energy as well as serve as a source of essential fatty acids. Lipid emulsions are as effective as glucose in conserving body nitrogen economy once absolute tissue requirements for glucose are met. The optimal percentage of calories that should be infused as fat is not known, but 20%–30% of total calories are reasonable for most patients. The infusion rate should not exceed 1.0 kcal/kg/h (0.11 g/kg/h) as most complications reported have occurred when providing more than this amount.3 A rate of 0.03–0.05 g/kg/h is adequate for most patients receiving continuous CPN. Lipid emulsions should not be used in patients with triglyceride concentrations >400 mg/dL. Moreover, patients at risk for hypertriglyceridemia should have serum triglyceride concentrations checked at least once during lipid emulsion infusion to ensure adequate clearance. Underfeeding obese patients by the amount of lipid calories that would normally be given (e.g., 20%–30% of calories) facilitates mobilization of endogenous fat stores for fuel and may improve insulin sensitivity. IV lipids should still be administered twice weekly to these patients to provide essential fatty acids. A recent meta-analysis of 49 RCTs demonstrated that use of ω-3 fatty-acid-enriched parenteral nutrition compared to standard parenteral nutrition leads to reduction in infection, sepsis, and ICU and hospital stay length.4
Peripheral Parenteral Nutrition
- Peripheral parenteral nutrition is of limited utility due to high risk of thrombophlebitis.
- Appropriate management of peripheral parenteral nutrition can increase the life of a single infusion site to >10 days. The following guidelines are recommended:
- Provide at least 50% of total energy as a lipid emulsion piggybacked with the dextrose–amino acid solution.
- Add 500–1000 units of heparin and 5 mg of hydrocortisone per liter (to decrease phlebitis).
- Place a fine-bore 22- or 23-gauge polyvinylpyrrolidone-coated polyurethane catheter in as large a vein as possible in the proximal forearm using sterile technique.
- Place a 5-mg glycerol trinitrate ointment patch (or 0.25 in of 2% nitroglycerin ointment) over the infusion site.
- Infuse the solution with a volumetric pump.
- Keep the total infused volume <3500 mL/d.
- Filter the solution with an inline 1.2-m filter.
Long-Term Home Parenteral Nutrition
- Long-term home parenteral nutrition is usually given through a tunneled catheter or an implantable subcutaneous port inserted in the subclavian vein.
- Nutrient formulations can be infused overnight to permit daytime activities in patients who are able to tolerate the fluid load. IV lipids may not be necessary in patients who are able to ingest and absorb adequate amounts of fat.
- Appropriate patient selection for home TPN is crucial due to high complication rates (∼50% at 6 months). Risk factors for complications include the use of a nontunneled or multilumen catheter, use of the catheter for blood draws, infusion of nonparenteral medications, use of lipid infusions, anticoagulation, older age, and open wounds.5
- Complications at time of line placement include pneumothorax, air embolism, arterial puncture, hemothorax, and brachial plexus injury.
- Thrombosis and pulmonary embolism: Radiologically evident subclavian vein thrombosis occurs commonly; however, clinical manifestations (upper extremity edema, superior vena cava syndrome) are rare. Fatal microvascular pulmonary emboli can be caused by nonvisible precipitate in parenteral nutrition solutions. Inline filters should be used with all solutions to minimize the risk of emboli.
- Fluid overload.
- Specific nutrient deficiencies. Consider providing supplemental thiamine (100 mg for 3–5 days) during initiation of CPN in patients at risk of thiamine deficiency (e.g., alcoholism).
- Hyperglycemia. In most patients, a blood glucose concentration of 140–180 mg/dL should be targeted during TPN infusion. Management of patients with hyperglycemia or type 2 diabetes can be performed in several ways:
- If blood glucose is >200 mg/dL, consider improving blood glucose control before starting CPN.
- If CPN is started, (1) limit dextrose to <200 g/d, (2) add 0.1 unit of regular insulin for each gram of dextrose in CPN solution (e.g., 15 units for 150 g), (3) discontinue other sources of IV dextrose, and (4) order routine, regular insulin with blood glucose monitoring by finger stick every 4–6 hours or IV regular insulin infusion with blood glucose monitoring by finger stick every 1–2 hours.
- In outpatients who use insulin, an estimate of the reduction in blood sugar that will be caused by the administration of 1 unit of insulin may be calculated by dividing 1500 by the total daily insulin dose (e.g., for a patient receiving 50 units of insulin as an outpatient, 1 unit of insulin may be predicted to reduce plasma glucose concentration by 1500/50 = 30 mg/dL).
- If blood glucose remains >200 mg/dL and the patient has been requiring SC insulin, add 50% of the supplemental short-acting insulin given in the last 24 hours to the next day’s CPN solution and double the amount of SC insulin sliding-scale dose for blood glucose values >200 mg/dL.
- The insulin-to-dextrose ratio in the CPN formulation should be maintained while the CPN dextrose content is changed.
- Catheter-related sepsis is the most common life-threatening complication in patients receiving CPN. The responsible microorganisms are most often skin flora: Staphylococcus epidermidis and Staphylococcus aureus.
- In immunocompromised patients and those receiving CPN for >2 weeks, Enterococcus, Candida species, Escherichia coli, Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Proteus, and Xanthomonas should be considered.
- The principles of evaluation and management of suspected catheter-related infection are outlined in Chapter 14, Treatment of Infectious Diseases.
- Use of sterile technique during connection of TPN, avoiding access of the TPN lumen of the central catheter for other purposes, and ensuring that TPN is never disconnected and restarted can reduce the risk of infection. Microorganisms can form biofilms on the intraluminal surface of the catheter and once attached they are difficult to eliminate. In patients on home TPN, ethanol lock therapy has been shown to be effective in reducing the rate of catheter-related infection.6
Although these abnormalities are usually benign and transient, more serious and progressive disease may develop in a subset of patients, usually after 16 weeks of CPN therapy or in those with short bowel syndrome.
- Biochemical: Elevated aminotransferases and alkaline phosphatase are commonly seen.
- Histologic alterations: Steatosis, steatohepatitis, lipidosis, phospholipidosis, cholestasis, fibrosis, and cirrhosis have all been seen.
- Biliary complications as listed below usually occur in patients who receive CPN for >3 weeks:
- Acalculous cholecystitis
- Gallbladder sludge
- Strategies to prevent hepatobiliary complications in patients receiving long-term CPN include providing a portion (20%–40%) of calories as fat, cycling CPN so that the glucose infusion is stopped for at least 8–10 hours per day, encouraging enteral intake to stimulate gallbladder contraction and maintain mucosal integrity, and avoiding excess calories and hyperglycemia.
- If biochemical or other evidence of liver damage occurs, evaluation for other causes of liver disease should ensue.
- If mild hepatobiliary complications develop, parenteral nutrition should not necessarily be discontinued. Rather, the same principles used in preventing hepatic complications can be applied therapeutically.
- When cholestasis is present, copper and manganese should be removed from the CPN formula to prevent accumulation in the liver and basal ganglia. A 4-week trial of metronidazole or ursodeoxycholic acid can be helpful in some patients.
Metabolic Bone Disease
- Metabolic bone disease has been observed in patients receiving CPN for >3 months
- Patients may be asymptomatic. Clinical manifestations include bone fractures and pain. Demineralization may be seen on radiologic studies. Osteopenia, osteomalacia, or both may be present.
- The precise causes of metabolic bone disease are not known, but several mechanisms have been proposed, including aluminum toxicity, vitamin D toxicity, and negative calcium balance.
- Several therapeutic options should be considered in patients who have evidence of bone abnormalities.
- Remove vitamin D from the CPN formulation if parathyroid hormone and 1,25-hydroxy vitamin D levels are low.
- Reduce protein to <1.5 g/kg/d as amino acids can cause hypercalciuria.
- Maintain normal magnesium status because magnesium is necessary for normal parathormone action and renal conservation of calcium.
- Provide oral calcium supplements of 1–2 g/d.
- Consider bisphosphonate therapy to decrease bone resorption.
- Monitoring nutrition support
- Adjustment of the nutrient formulation is often needed as medical therapy or clinical status changes.
- When nutrition support is initiated, other sources of glucose (e.g., peripheral IV dextrose infusions) should be stopped and the volume of other IV fluids adjusted to account for CPN.
- Vital signs should be checked every 8 hours.
- In certain patients, body weight, fluid intake, and fluid output should be followed daily.
- Serum electrolytes (including phosphorus) should be measured every 1–2 days after CPN is started until the values are stable and then rechecked weekly.
- Serum glucose should be checked up to every 4–6 hours by finger stick until blood glucose concentrations are stable and then rechecked weekly.
- If lipid emulsions are being given, serum triglycerides should be measured during lipid infusion in patients at risk for hypertriglyceridemia to demonstrate adequate clearance (triglyceride concentrations should be <400 mg/dL).
- Careful attention to the catheter and catheter site can help to prevent catheter-related infections.
- Gauze dressings should be changed every 48–72 hours or when contaminated or wet. Transparent dressings can be changed weekly.
- Tubing that connects the parenteral solutions with the catheter should be changed every 24 hours.
- A 0.22-μm filter should be inserted between the IV tubing and the catheter when lipid-free CPN is infused and should be changed with the tubing.
- A 1.2-μm filter should be used when a total nutrient admixture containing a lipid emulsion is infused.
- When a single-lumen catheter is used to deliver CPN, the catheter should not be used to infuse other solutions/medications (apart from compatible antibiotics) or to monitor central venous pressure.
- When a triple-lumen catheter is used, the distal port should be reserved solely for the administration of CPN.
Refeeding the Severely Malnourished Patient
Refeeding syndrome may occur after initiating nutritional therapy in patients who are severely malnourished and have had minimal nutrient intake.
- Hypophosphatemia, hypokalemia, and hypomagnesemia: Rapid and marked decreases in these electrolytes occur during initial refeeding because of insulin-stimulated increases in cellular mineral uptake from extracellular fluid. For example, plasma phosphorus concentration can fall below 1 mg/dL and cause death within hours of initiating nutritional therapy if not adequately replaced. Suggested replacement guidelines are reviewed in several sources.7,8,9
- Fluid overload and congestive heart failure are associated with decreased cardiac function and insulin-induced increases in sodium and water reabsorption in conjunction with nutritional therapy containing water, glucose, and sodium. Renal mass may be reduced, limiting the ability to excrete salt or water loads.
- Cardiac arrhythmias: Patients who are severely malnourished often have bradycardia. Sudden death from ventricular tachyarrhythmias can occur during the first week of refeeding in severely malnourished patients and may be associated with a prolonged QT interval and electrolyte abnormalities. Patients with ECG changes should be monitored on telemetry, possibly in an ICU.
- Glucose intolerance: Starvation causes insulin resistance such that refeeding with high-carbohydrate meals or large amounts of parenteral glucose can cause marked elevations in blood glucose concentration, glycosuria, dehydration, and hyperosmolar coma. In addition, carbohydrate refeeding in patients who are depleted in thiamine can precipitate Wernicke encephalopathy.
Management of Severe Malnutrition
- Careful evaluation of cardiovascular function and plasma electrolytes (history, physical examination, ECG, and blood tests) and correction of abnormal plasma electrolytes are important before initiation of feeding.
- Refeeding by the oral or enteral route involves frequent or continuous administration of small amounts of food or an isotonic liquid formula.
- Parenteral supplementation or complete parenteral nutrition may be necessary if the intestine cannot tolerate feeding.
- During initial refeeding, fluid intake should be limited to approximately 800 mL/d plus insensible losses. Adjustments in fluid and sodium intake are needed in patients who have evidence of fluid overload or dehydration.
- Changes in body weight provide a useful guide for evaluating the efficacy of fluid administration. Weight gain >0.25 kg/d or 1.5 kg/wk probably represents fluid accumulation in excess of tissue repletion. Initially, approximately 15 kcal/kg (containing approximately 100 g carbohydrate and 1.5 g protein per kilogram of actual body weight) should be given daily.
- The rate at which caloric intake can be increased depends on the severity of malnutrition and tolerance to feeding. In general, increasing by 2–4 kcal/kg every 24–48 hours is appropriate.
- Sodium should be restricted to approximately 50 mEq/m2 body surface area/day, but liberal amounts of phosphorus, potassium, and magnesium should be given to patients with normal renal function.
- All other nutrients should be given in amounts needed to meet the recommended dietary intake (Table 2-7).
- Body weight, fluid intake, urine output, plasma glucose, and electrolyte values should be monitored daily during early refeeding (first 3–7 days) so that nutritional therapy can be appropriately modified when necessary.
|Mineral||Recommended Daily Enteral Intake/Parenteral Intake10||Signs and Symptoms of Deficiency||Signs and Symptoms of Toxicity||Diagnostic Evaluation|
|Sodium||1.2–1.5 ga/1–2 mEq/kg||Encephalopathy, seizure, weakness, dehydration, cerebral edema9||Encephalopathy, seizure||Sodiump (correct for hyperglycemia)|
Sodiumu (will often only provide a rough estimate [i.e., too low, too high])
|Potassium||4700 mg(11)a/1–2 mEq/kg||Abdominal cramping, diarrhea, paresthesias, QT prolongation, weakness||QRS widening, QT shortening (sine wave morphology in extreme cases), peaked T waves||Potassiumw,b|
|Calcium||1000–1200 mg/10–15 mEq||QRS widening, paresthesias (Trousseau sign), tetany (Chvostek sign), osteomalacia||Encephalopathy, headache, abdominal pain, nephrolithiasis, metastatic calcification||Calciumw,b, 24-h calciumu (correct for albumins)|
|Magnesium||420 mg/8–20 mEq||Tachyarrhythmia, weakness, muscle cramping, peripheral and central nervous system overstimulation (seizure, tetany)||Hyporeflexia, nausea, vomiting, weakness, encephalopathy, decreased respiratory drive, hypocalcemia, hyperkalemia, heart block||Magnesiums, magnesiumu|
|Phosphorus||700 mg/20–40 mmol||Weakness, fatigue, increased cell membrane fragility (hemolytic anemias, leukocyte + platelet dysfunction), encephalopathy||Metastatic calcification, theoretic higher risk of nephrolithiasis, secondary hyperparathyroidism||Phosphorusp|
Subscript: b, blood; p, plasma; s, serum; u, urine; w, whole blood.
aNote: Adequate daily intake.
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