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Total Parenteral Nutrition (TPN) Solutions  

Parenteral nutrition is by definition given IV. Partial parenteral nutrition supplies only part of daily nutritional requirements, supplementing oral intake. Many hospitalized patients receive dextrose or amino acid solutions by this method. Total parenteral nutrition (TPN) supplies all daily nutritional requirements. TPN can be used in the hospital or at home. Because TPN solutions are concentrated and can cause thrombosis of peripheral veins, a central venous catheter is usually required.

Indications:
TPN is indicated for patients whose GI tract is not functional. A general but untested indication is anticipation of undernutrition (< 50% of metabolic needs met) for > 7 days. TPN is given before and after treatment to severely undernourished patients who cannot ingest large volumes of oral feedings and are being prepared for surgery, radiation therapy, or chemotherapy. TPN may reduce morbidity and mortality after major surgery, severe burns, and head trauma, especially in patients with sepsis. Patients with disorders requiring complete bowel rest (eg, some stages of Crohn's disease, ulcerative colitis, severe pancreatitis) or with pediatric GI disorders (eg, congenital anomalies; prolonged diarrhea, regardless of its cause) often respond well to TPN.

Nutritional content:
TPN requires water (30 to 40 mL/kg/day), energy (30 to 60 kcal/kg/day, depending on energy expenditure), amino acids (1 to 2.0 g/kg/day, depending on the degree of catabolism), essential fatty acids, vitamins, and minerals (see Table 2: Nutritional Support: Basic Adult Daily Requirements for Total Parenteral Nutrition). Children who need TPN may have different fluid requirements and need more energy (120 kcal/kg/day) and amino acids (2.5 to 3.5 g/kg/day).

Basic TPN solutions are prepared using sterile techniques, usually in liter batches according to standard formulas. Normally, 2 L/day of the standard solution is needed. Solutions may be modified based on laboratory results, underlying disorders, hypermetabolism, or other factors. Commercially available lipid emulsions are often added to supply essential fatty acids and triglycerides; 20 to 30% of total calories is usually supplied as lipids. However, withholding lipids and their calories may help obese patients mobilize endogenous fat stores, increasing their insulin sensitivity.

Solutions:
Many solutions are commonly used. Electrolytes can be added to meet the patient's needs.

Patients who have renal insufficiency and are not receiving dialysis or who have liver failure require solutions with reduced protein content and a high percentage of essential amino acids. For patients with heart or kidney failure, volume (liquid) intake must be limited. For patients with respiratory failure, a lipid emulsion must provide most of nonprotein calories to minimize CO2 production by carbohydrate metabolism. Neonates require lower dextrose concentrations (17 to 18%).

Beginning TPN administration: Because the central venous catheter needs to remain in place for a long time, strict sterile techniques must be used during insertion and maintenance. The TPN line should not be used for any other purpose. External tubing should be changed q 24 h with the first bag of the day. In-line filters are controversial and may not help. Dressings should be kept sterile and are usually changed q 48 h using strict sterile techniques. For TPN given outside the hospital, patients must be taught to recognize symptoms of infection, and qualified home nursing must be arranged.

The solution is started slowly at 50% of the calculated requirements, using 5% dextrose to make up the balance of fluid. Energy and nitrogen should be given simultaneously. The amount of regular insulin given (added directly to the TPN solution) depends on the blood glucose level; if the level is normal and the final solution contains the usual 25% dextrose concentration, the usual starting dose is 5 to 10 units of regular insulin /L of TPN fluid.

Monitoring: Progress should be followed on a flowchart. An interdisciplinary nutrition team, if available, should monitor the patient. Weight, CBC, electrolytes, and BUN should be monitored often (eg, daily for inpatients). Blood glucose should be monitored q 6 h until stable. Fluid intake and output should be monitored continuously. When the patient becomes stable, blood tests can be done much less often.

Liver function tests should be done. Plasma proteins (eg, serum albumin, possibly transthyretin or retinol-binding protein); prothrombin time; plasma and urine osmolality; and Ca, Mg, and phosphate (not during glucose infusion) should be measured twice/wk. Full nutritional assessment (including BMI calculation and anthropometric measurements—see Undernutrition: Physical examination; see Obesity and the Metabolic Syndrome: Body composition analysis) should be repeated at 2-wk intervals.

Complications:
With close monitoring by a nutrition team, the complication rate may be < 5%. Complications may be related to the central venous catheter (see Table 5: Approach to the Critically Ill Patient: Complications Associated With Central Venous Lines) or to the provision of nutrition.

Glucose abnormalities are common. Hyperglycemia can be avoided by monitoring blood glucose often, adjusting the insulin dose in the TPN solution, and giving subcutaneous insulin as needed. Hypoglycemia can be precipitated by suddenly discontinuing constant concentrated dextrose infusions. Treatment, depending on the degree of hypoglycemia, may consist of 50% dextrose IV or infusion of 5 or 10% dextrose for 24 h before resuming TPN via the central venous catheter.

Abnormalities of serum electrolytes and minerals should be corrected by modifying subsequent infusions or, if correction is urgently required, by beginning appropriate peripheral vein infusions. Vitamin and mineral deficiencies are rare if solutions are given correctly. Elevated BUN may reflect dehydration, which can be corrected by giving free water as 5% dextrose via a peripheral vein.

Volume overload (suggested by > 1 kg/day weight gain) may occur when high daily energy requirements require large fluid volumes.

Metabolic bone disease, or bone demineralization (osteoporosis or osteomalacia), develops in some patients receiving TPN for > 3 mo. The mechanism is unknown. Advanced disease can cause severe periarticular, lower extremity, and back pain. Temporarily or permanently discontinuing TPN is the only known treatment.

Adverse reactions to lipid emulsions (eg, dyspnea, cutaneous allergic reactions, nausea, headache, back pain, sweating, dizziness) are uncommon but may occur early, particularly if lipids are given at > 1.0 kcal/ kg/h. Temporary hyperlipidemia may occur, particularly in patients with kidney or liver failure; treatment is usually not required. Delayed adverse reactions to lipid emulsions include hepatomegaly, mild elevation of liver enzymes, splenomegaly, thrombocytopenia, leukopenia, and, especially in premature infants with respiratory distress syndrome, pulmonary function abnormalities. Temporarily or permanently slowing or stopping lipid emulsion infusion may prevent or minimize these adverse reactions.

Hepatic complications include liver dysfunction, painful hepatomegaly, and hyperammonemia. They can develop at any age but are most common among infants, particularly premature ones (whose livers are immature). Transient liver dysfunction, evidenced by increased transaminases, bilirubin, and alkaline phosphatase, is common with the initiation of TPN. Delayed or persistent elevations may result from excess quantities of amino acids. Pathogenesis is unknown. Contributing factors probably include cholestasis and inflammation. Progressive fibrosis occasionally develops. Reducing protein delivery may help. Painful hepatomegaly suggests fat accumulation; carbohydrate delivery should be reduced. Hyperammonemia can develop in infants. Signs include lethargy, twitching, and generalized seizures. Correction consists of arginine supplementation at 0.5 to 1.0 mmol/kg/day. For infants who develop any hepatic complication, limiting amino acids to 1.0 g/kg/day may be necessary.

Gallbladder complications include cholelithiasis, gallbladder sludge, and cholecystitis. These complications can be caused or worsened by prolonged gallbladder stasis. Stimulating contraction by providing about 20 to 30% of calories as fat and stopping glucose infusion several hours a day is helpful. Oral or enteral intake also helps. Treatment with metronidazole, ursodeoxycholic acid, phenobarbital, or cholecystokinin helps some patients with cholestasis.

Last full review/revision November 2005    

REF: http://www.merck.com/mmpe/sec01/ch003/ch003c.html#sec01-ch003-ch003c-217  

Indications for Total Parenteral Nutrition   (REF: Rakel: Conn's Current Therapy 2007)

Critical illness

• EN  (enteral nutrition) preferred; TPN may be necessary during low flow states to supplement enteral feeding; prolonged ileus
• PN glutamine shown benefit PN lipids containing n-3 FA, MCT, MUFA beneficial

Acute pancreatitis

• EN preferred; TPN as alternative in those without jejunal enteral access, severe ileus; combined with EN when it's not fully tolerated, hemodynamic instability
• PN lipids do not exacerbate disease; n-3 FAs, MCT lipids preferred

Hepatic failure

• EN preferred; TPN if active GI bleeding, bowel obstruction, hemodynamic instability, supplement to enteral
• High BCAA formulations for refractory HE

Renal failure

• EN preferred; TPN if enteral contraindicated or needs supplementing
• Use of standard amino acid solutions preferred more than those containing low amounts of nonessential amino acids

SBS (short bowel syndrome)

• TPN initially until patient stable, fluid/electrolyte balance maintained; introduce enteral feeding slowly, monitor for tolerance, wean TPN accordingly
• Additional vitamins and trace elements may be required for stool outputs >1 L/d

Enterocutaneou fistula

• TPN initially until patient stable, fluid/electrolyte balance maintained; introduce enteral feeding slowly, monitor for tolerance, wean TPN accordingly
• Additional vitamins, trace elements, protein, and fluid outputs >500 mL/d

[Abbreviations: BCAA = branched-chain amino acid; EN = enteral nutrition; FA = fatty acid; GI = gastrointestinal; HE = hepatic encephalopathy; MCT = medium- chain triglyceride; MUFA = monounsaturated fatty acid; PN = parenteral nutrition; SBS = short bowel syndrome; TPN = total parenteral nutrition. ]

CURRENT TPN THERAPY

• Evaluate need for PN (parenteral nutrition): Enteral feeding not indicated.

• Enteral nutrient provision inadequate (e.g., <60% nutritional needs tolerated for >7 days).

• Perform nutrition assessment: Calculate or measure energy requirements.

• Estimate protein requirements.
• Estimate fluid requirements.

• Calculate PN formulation: Protein: 1 to 2 g/kg per day (dependent on disease state and medical intervention).

• Dextrose: 40% to 60% kcal per day (2 to 5 mg/kg/min per day).
• Lipid: 10% to 30% kcal per day.
• Electrolytes per needs reflected in laboratory measurements and medical interventions.
• Vitamins, minerals based upon disease state.
• Extra fluid if need to meet fluid needs solely via parenteral feeding.

• Monitor daily clinical status, laboratory values, fluid status, and adjust parenteral formulation as needed.

Sample Total Parenteral Nutrition Macronutrient Calculation

• Energy needs: 2000 kcal/d.

• Protein needs: 120 g/d.

• Fluid needs: 2400 mL/d.

• TPN: Protein contains 4 kcal/g, so 120 g protein = 480 kcal.2000 total kcal - 480 protein kcal = 1520 kcal (to provide as nonprotein kcal).

• Lipid: 1520 kcal × 0.25 = 380 kcal. Provided as 20% Intralipid: has 2 kcal/mL (380 kcal ÷ 2 kcal/mL) = 190 mL Intralipid.

• Dextrose: 1520 kcal × 0.75 = 1140 kcal.

• Dextrose has 3.4 kcal/g (1140 kcal ÷ 3.4 kcal/g) = 335 g dextrose.
• Volume (using 10% amino acid, and 70% dextrose solutions).

• Protein: 120 g ÷ 0.1 = 1200 mL.

• Dextrose: 335 g ÷ 0.7 = 478 mL.

• Lipid: 190 mL.

• Electrolytes and other additives: approximately 100 mL.

• Total volume = 1968 mL.

• Fluid needs: 430 mL sterile water.

REF: Goldman: Cecil Medicine 2007, 23rd ed

Parenteral nutrition formulations classically contain glucose concentrations ranging from 5 to 70%; the selection depends on the estimated calorie needs and the total volume requirement.  The oxidation of 1 g of glucose yields 4 kcal.

In parenteral nutrition, nitrogen is administered as amino acids containing all essential and almost all nonessential amino acids. Amino acids are a source of calories and precursors for the biosynthesis of proteins involved in almost every body function. Protein can be oxidized and yields 4 kcal/g.
The standard formulations for amino acids include solutions containing amino acids only or combinations of amino acids with glucose. Standard amino acid solutions are also available with or without electrolytes.

Fat emulsions are available in concentrations of 10%, 20%, and 30%.
Use of lipids as an energy source can have important benefits. Oxidation of 1 g of intravenous fat supplies 9 kcal. It allows a reduced prescription of parenteral glucose and can thereby reduce the risk or severity of hyperglycemia, especially in stressed patients with insulin resistance. Only 10% of parenteral nutrition is needed as fat to meet essential fatty acid needs. However, most parenteral nutrition formulations now contain 15 to 40% as lipids. Adults usually receive 0.5 to 1.5 g/kg/day. In patients with hypertriglyceridemia (more than 4 to 5 mmol/L or 350 to 400 mg/dL), lipid emulsions should not be started or should be temporarily interrupted.

IV Solutions

D 5W = 5%D/W     => (5 gm/100 mL) 50 gm/L glucose (278 mmol/L glucose), 252 mOsm/kg osmolality  |  170 calories/Liter

D10W = 10% D/W => 100 gm/L glucose, 505 mOsm/kg  |  340 calories/Liter

D50W = 50% D/W => 500 gm/L glucose, 2520 mOsm/kg

Normal saline/NS = 0.9% NaCl => 154 mEq/L Na, 154 mEq/L Cl, 308 mOsm/kg

1/2 NS = 0.45% NaCl => 77 mEq/L Na, 77 mEq/L Cl, 154 mOsm/kg   

3% NS = 3% NaCl => 513 Meq/L Na, 513 mEq/L Cl, 1026 mOsm/kg

Ringer's lactate => 130 mEq/L Na, 109 mEq/L Cl, 4 mEq/L K, 3 mEq/L Ca, 28 mEq/L lactate 

1 ampule of 50 mL 7.5% NaBicarbonate =>   44.6 mEq/amp Na HCo3 

1 ampule of 10 mL 10% CaCl => 13.6 mEq/amp CaCl

1 ampule of 10 mL 10% Ca-gluconate => 4.6 mEq/amp of Ca-gluconate

1 ampule of 15 mL 42% Na-phosphate => 3 mmol/L phosphate, 4 mEq/L Na

1 ampule of 15 mL 46% K-phosphate => 3 mmol/L phosphate, 4.4 mEq/L K

1 ampule of 10 mL 50% Mg-sulfate => 40.6 mEq/amp Mg-sulfate

In dehydrated patients with presumed normal total body sodium content,
Body water deficit = desired TBW - current TBW

• Desired TBW = [Measured serum Na (mEq/L) x current TBW] / 140 mEq/L
• Current TBW (L) = 0.6 x current body weight (kg)

Minimal urine output is usually over 500 mL/day in adults.
Normally, daily Na supplement is about 50-150 mEq/day, & daily K supplement is about 20-60 mEq/day in adequate renal function patients.

2008