It has been estimated that up to 50% of hospitalized small animal patients are malnourished. Malnutrition and wasting contribute to many aspects of critical illness including impaired immune function, increased susceptibility to infection, delayed wound healing, decreased strength and vigor, and increased morbidity and mortality. Indeed, malnutrition has been implicated as a significant factor that influences outcome in critically ill humans. Therefore, prevention of malnutrition by ensuring adequate nutrient intake is crucial in the management of critically ill patients. It has been well established that nutritional support in critically ill patients will decrease morbidity and mortality, improve tolerance to invasive procedures, shorten hospitalization periods, decreased incidence of infections, enable earlier ambulation, hasten wound healing, and reduce complications.

Parenteral nutrition involves the administration of essential nutrients by intravenous infusion. Parenteral nutrition should be used only when enteral feeding is not possible. Parenteral nutrition is complicated and more expensive compared with enteral nutrition. Parenteral nutrition is associated with a risk of infection from the catheter site and villous atrophy of the small intestine, which may increase the risk of bacterial translocation and sepsis. There are two different ways to administer parenteral nutrition, either peripherally or what is also known as partial parenteral nutrition (PPN) or centrally, which is typically, referred to as total parenteral nutrition (TPN). TPN solutions are very hypertonic (>1500 mOsm/L) and must be administered into a large central vein to minimize the incidence of phlebitis and thrombosis. PPN solutions are formulated with an osmolality less than 600 mOsm/L and hence may be administered into a peripheral vein.

Clinical Evaluation

When to initiate nutritional support requires early assessment of the patient to identify those either at risk of malnutrition or who already require nutritional support. Nutritional assessment involves evaluation of the history, physical examination, body weight (BW), body condition score (BCS) and laboratory data. The type, amount and frequency of food intake and the incidence of vomiting should be noted. Manifestations of inadequate nutrient intake include loss of BW or BCS, hypoalbuminemia, and anemia. Alterations of common laboratory indicators of malnutrition (albumin, BUN, cholesterol, creatinine kinase, RBC's and lymphocyte counts) are often indistinguishable from those that can occur with concurrent disease. Other markers of nutritional status such as prealbumin, transferrin, total iron binding capacity, fibronectin, retinal binding protein, ceruloplasmin, a-1-antitrypsin, a-1-acid glycoprotein and C-reactive protein have not been fully evaluated in feline and canine patients.

Indications for Parenteral Nutrition

Indications for nutritional support include a history of illness or weight loss, current poor body condition or acute loss of >5% body weight, a history of anorexia or inappetence for >3 days (real or anticipated), the presence of injuries which prevent adequate oral intake (facial injuries, prolonged or unmanaged pain, injuries requiring surgical correction), severe protracted vomiting, ileus, small intestinal obstruction, pancreatitis, and patients who cannot guard the respiratory tract (e.g., severe neurological disease, coma etc).

Nutritional Requirements

The calculation of energy requirements of critically ill patients has been the subject of controversy. Direct measurement of a patient's energy consumption is not readily available. Consequently, several equations have been recommended to estimate the requirement.

These equations utilize the resting energy requirements (RER), basal energy requirements (BER), or maintenance energy requirements (MER). Basal energy requirements describe the energy that is needed to meet the needs of cells and organs under a stress free, thermoneutral environment, and in a post-absorptive state. The resting energy requirements (RER) accounts for the energy required by the animal in a resting state and include physiologic influences and the assimilation of nutrients. The RER can be calculated as 70 x BW (kg)^0.75kcal/day. The maintenance energy requirements (MER) encompass all the energy required for maintaining normal body condition in a normal pet.

Some authors have recommended multiplying the RER with an illness factor (0.5-2.0) to account for hypermetabolism. Other authors suggest that the RER of critical patients, determined with indirect calorimetry, indicates that their energy expenditure is only slightly increased from normal. Feeding excess calories can be associated with respiratory complications, electrolyte imbalances and hepatic dysfunction. Hence is it is generally recommended to avoid overfeeding the critically ill patient. Therefore the practical recommendation is to ensure that all patients are fed at a minimum level of their RER. Close monitoring of the patient's body weight and body condition can then be used to help to adjust the calorie intake for each individual patient.

The intent of parenteral support is to provide the resting energy requirement while avoiding complications. The risk of thrombophlebitis depends on both the osmolality of the solution and the rate at which the hyperosmolar solution is administered. PPN solutions which are administered via a peripheral vein must be formulated with an osmolality less than 600 mOsm/L. Therefore for peripheral parental nutrition, a compromise must be reached between the osmolality of the solution, the rate the solution is administered, and the calories that can be administered. Hence, PPN solutions can only provide a portion, rather the total energy requirement of the patient to avoid the development of thrombophlebitis. TPN solutions are very hypertonic (>1500 mOsm/L) and must be administered into a large central vein to minimize the incidence of phlebitis and thrombosis.

Parenteral Solutions

Calories can be provided to the critically ill patient by a balance of fat, amino acids, and dextrose. The ratio of dextrose to lipid should be selected to reflect the hormonal milieu and metabolic condition of the liver. High fat diets have been recommended because free fatty acids rather than glucose provide the principal fuel in the catabolic patient. The use of lipids in parenteral nutrition has been controversial due to the association between hyperlipidemia and pancreatitis. Nevertheless, lipid emulsions have been successfully utilized in dogs and humans with pancreatitis when the patient is not hypertriglyceridemic prior to institution of parenteral therapy. Intralipid is isotonic, which helps to lower the osmolality of the final solution. Indeed, some authors have suggested that PPN solutions could contain >90% lipid. However, supplementation with dextrose may help to preserve lean body mass by down regulating gluconeogenesis. Excess dextrose should be avoided as it can predispose to hyperglycemia. The subsequent release of insulin may lead to or exacerbate hypophosphatemia, hypokalemia, and other metabolic derangements.

Protein recommendations for parenteral nutrition range from 3 to 6 g/100 kcal. The amount of protein prescribed depends on the ability to dispose of nitrogenous waste products (i.e., absence of azotemia and hyperammonemia) balanced with provision of adequate protein for tissue synthesis and repair. To abolish negative nitrogen balance in a severely hypermetabolic and hypercatabolic patient, it may be necessary to supply protein in amounts considerably in excess of normal minimum requirements. A variety of amino acid solutions are available for use in parenteral nutrition. A principle difference is the presence or absence or electrolytes in the amino acid solution. Amino acid solutions without electrolytes have a lower osmolality, hence are appropriate in the formation of PPN solutions.

Glutamine has an important role in acid-base balance, as a precursor of purine and pyrimidine nucleotides, a role in detoxification, as a nitrogen carrier between tissues, as a regulator of hepatic protein synthesis, and as a respiratory fuel in certain tissues. Glutamine is a particularly important substrate in rapidly dividing cells, such as those of the gastrointestinal tract and the immune system. Glutamine is responsible for maintaining the IgA-secreting cells of the gut mucosa, and an adequate supply is required to ensure the integrity of the intestinal mucosal barrier. Glutamine has been described as a "conditionally essential amino acid". Increased demand coupled with poor supply in critical patients may result in compromise of the gut mucosal barrier, with subsequent bacterial translocation and systemic infection. Although glutamine has been recommended to prevent gastrointestinal atrophy and to maintain intestinal integrity, it is not typically included in parenteral solutions because intravenous preparations are difficult to obtain.

The parenteral solution should be formulated to contain 40 mEq/L of potassium to compensate for the insulin mediated transcellular potassium shift associated with refeeding. Refeeding has also been associated with a transcellular phosphorus shift due to the increased production of high phosphate compounds. Therefore, it has been recommended that parenteral solutions contain a minimum 5-10 mM/L of phosphorus. Water soluble vitamins can be provided by the addition of a multivitamin B complex preparation. These preparations typically do not include folic acid due to incompatibility with riboflavin in solution. Fat soluble vitamins, trace elements, and calcium are not generally included in the parenteral nutrition solution if the duration of treatment is expected to be less than 1-2 weeks. The addition of calcium is not routine because of the risk of precipitation of the parenteral solution, and calcium deficiency appears to be well tolerated in the short term. The dose of trace minerals to include in the parenteral nutrition is uncertain. Vitamin K should not be added to the parenteral nutrient solution, but should be administered subcutaneously once weekly.

Administration

The nutrient-rich parenteral solutions provide an ideal growth media for bacteria.

To minimize complications with infections, the solutions must be prepared and administered under sterile conditions through a dedicated catheter. Parenteral solutions should always be mixed in the following manner--dextrose, amino acids, and lipid, and refrigerated until use. Parenteral nutrition solutions should be administered for a maximum of 2 days before discarding. Although not absolutely necessary, the parenteral nutrition fluid bag and lines can be covered with aluminum to protect the amino acids and lipids from light degradation.

The rate of administration of parenteral solutions is limited by the fluid volume and osmolarity. Fluid volume is a concern particularly in cats and oliguric patients. When fluid volume is a concern, the energy density of the solution can be increased by using a higher ratio of lipid to dextrose. To minimize the risk of the refeeding syndrome, the parenteral nutrition infusion should begin at one third of the calculated requirement. It is administered via a dedicated catheter placed in the jugular vein. If there are no complications with feeding, the rate fed can be slowly increased to reach illness energy requirements by day 3.

Monitoring

Routine physical examinations including body temperature, heart rate, respiratory rate, twice daily weight measurements, assessment of hydration status, and attitude should be performed on all critically ill patients receiving nutritional support. Metabolic complications that may occur include hyperglycemia, glucosuria, hypo-or hyperkalemia, hypophosphatemia and lipemia. These may necessitate adjusting the nutrient ratios, slowing the rate of infusion, or administering insulin, potassium or phosphate supplements. To monitor for complications associated with the parenteral nutrition therapy, the packed cell volume, total protein, blood urea nitrogen, serum electrolytes (sodium, potassium, chloride, ionized calcium), venous blood gas and blood glucose concentrations should be monitored every 6 to 12 hours. Urine can be checked daily for glucosuria. Serum triglycerides and ammonia concentrations should be determined daily.

Calculation of Parenteral Nutritional Requirements

1.  Determine if solution is to be administered peripherally or centrally.

2.  Calculate the Resting Energy Requirement (RER)
RER = 70* BW(kg)^0.75 kcal

3.  Calculate the protein requirement at 3-6 grams protein per 100 kcal

4.  Calculate the ratio of dextrose to fat.

5.  Calculate the volumes of nutrient solutions required

a.  If peripheral, use 8.5% amino acid solution without electrolytes (85 g/L, 890 mOsm/L);
If central use 8.5% amino acid solution with electrolytes (85 g/L, 1160 mOsm/L)

b.  20% lipid solution (2 kcal/ml; 260 mOSm/L) to supply 10-90% of RER

c.  If peripheral, use 5% dextrose solution (0.17 kcal/ml, 253 mOSm/L)
If central, use 50% dextrose solution (1.7 kcal/ml, 2530 mOsm/L) to supply 10-90% of RER

6.  Consider potassium. - Aim is 40 mEq/L. Use potassium phosphate (4.4 mEq/ml) to provide the difference in potassium (i.e. the amino acid solution contains 60 mEq K/L)

7.  Consider phosphorus. Aim is 5-10 mM/L - (Potassium phosphate contains 3 mM/ml)
Amino acid solution contains 30 mM/L, lipid solution contains 15 mM/L

8.  Consider B vitamin requirements: 3ml/10kg multivitamin solution

9.  Calculate the total volume of the parenteral solution

10. Calculate the caloric content (without amino acids), and convert to kcal/L.

11. Calculate the osmolality of the solution (mOSm/L). Be sure to convert the osmolality to mOsm/L!

12. Decide if solution needs to be administered peripherally (< 600 mOsm/L) or centerally.

13. Calculate the delivery rate = ml/hr

14. Calculated daily maintenance fluid requirements

References

1.  Buffington CAT: Multi-center study: Food intake of hospitalized patients. Proceedings of the 16th ACVIM Forum, 1998, 14-16.

2.  Chan DL, Freeman LM, Labato MA, et al. Retrospective Evaluation of Partial Parenteral Nutrition in Dogs and Cats. J Vet Intern Med. 2002; 16: 440-45.

3.  Chandler ML, Guilford WG, Payne-James J. Use of Peripheral Parenteral Nutritional Support in Dogs and Cats. J Am Vet Med Assoc. 2000a; 216(5): 669-73.

4.  Chandler ML, Guilford WG, Maxwell A, et al. A Pilot Study of Protein Sparing in Healthy Dogs Using Peripheral Parenteral Nutrition. Res Vet Sci. 2000b; 69: 47-52.

5.  Lippert AC, Faulkner JE, Evants AT, Mullaney TP: Total parenteral nutrition in clinical normal cats. JAVMA 194(5):669-675, 1989.

6.  Lippert AC, Fulton RB, Parr AM. A Retrospective Study of the Use of Total Parenteral Nutrition in Dogs and Cats. J Vet Intern Med. 1993; 7: 52-64.

7.  Reuter JD, Marks SL, Rogers QR, et al. Use of Total Parenteral Nutrition in Dogs: 209 Cases (1988-1995). J Vet Emerg Crit Care. 1998; 8(3): 201-13.

8.  Rombeau JL, Caldwell MD. Clinical Nutrition. Parenteral Nutrition. Philadelphia: WB Saunders, 1993.

9.  Solomon SM, Kirby DF. The refeeding syndrome: a review. J Parenter Enteral Nutr 1990;14(1):90-96.