Parenteral Nutrition

Too frequently, veterinary patients do not receive their daily nutritional requirements as a result of inadequate nutrient intake [1]. Advancements in veterinary nutrition and critical care have directed us to provide more aggressive nutritional support to critically ill small animal patients. A lack of essential nutrients and energy can contribute to increased patient morbidity, impaired wound healing, immunosuppression, and increased mortality. The goals of nutritional support are to treat and prevent malnutrition during times of critical illness until the patient is able to assimilate enteral nutrients alone [2]. Although the gold standard for administration of nutritional support is to utilize and feed whatever portion of the gastrointestinal tract is functional, some animals either cannot or will not voluntarily eat, or cannot digest or absorb nutrients provided enterally because of severe vomiting, ileus, inflammation, or surgical resection of the gastrointestinal tract [2,3]. The use of enteral nutrition may be contraindicated or impossible in such cases, and alternate forms of nutrition become absolutely necessary.

Parenteral nutrition is the provision of nutrients by any method other than the gastrointestinal tract [4]. Parenteral nutrition usually contains some form of carbohydrate in the form of dextrose, lipid, and a protein source in addition to vitamins and minerals (Table 7-1). Various phrases have been used to describe the type and method of parenteral nutrition. The term "total parenteral nutrition" (TPN) has frequently been used to indicate the provision of all of a patient's essential nutritional requirements via intravenous, intraperitoneal, or intraosseous route [5,6]. Because we rarely are able to provide every essential macro- and micronutrient to veterinary patients, the term TPN is actually a misnomer that should be abandoned [4]. Another recommendation was to simply use the terminology "Parenteral Nutrition (PN)" to be more accurate [6].

Parenteral nutrition has also been named based on its route of administration. Solutions with an osmolality greater than 600 to 800 mOsm/L are typically infused via central venous catheters to prevent thrombophlebitis [7]. Such solutions have been called "central parenteral nutrition" [4]. Interest has been renewed in the infusion of solutions with lower osmolalities into peripheral veins. This is termed "peripheral parenteral nutrition" or "partial parenteral nutrition" (PPN). Peripheral parenteral nutrition should be considered when short-term nutritional support is required, or as a bridge between parenteral and enteral nutrition as a patient becomes able to tolerate enteral feedings.

Parenteral Nutrients

In the past, the administration of parenteral nutrition in veterinary patients has been limited, largely because of the perceived increased expense, risk of potential complications including sepsis, and lack of technical expertise required for the placement and maintenance of central venous catheters [7,8 ]. Advancements in veterinary critical care have largely made parenteral nutrition a more viable option for critically ill small animal patients [8]. Parenteral nutrition can be formulated in-house or by commercial pharmacies by compounding a mixture of amino acids, dextrose, lipids, and vitamins [7]. "Three-in-One" mixtures can also be purchased from commercial sources. Ideally, parenteral nutrition solutions should be formulated and mixed under strict aseptic conditions, either in a compounding machine or in a laminar flow hood. In private practice, however, such techniques are often not possible. Mixing should occur, instead, in a surgical suite or low-traffic area, with the personnel wearing a surgical cap, mask, and sterile gloves.

Proteins

Essential and nonessential crystalline amino acid solutions (3.5%, 8.5%, and 15%) are available as a protein source for veterinary parenteral nutrition formulations. Most commonly, an 8.5% solution is used for small animal patients [6]. Amino acid solutions have a high osmolarity (300 - 1400 mOsm/L) and a relatively acidic pH (5.3 - 6.5) [6,9,10]. It has been recommended that amino acid solutions with concentrations greater than 3.5% should not be administered through a peripheral vein because of the high osmolality [10]. Commercial products containing varying amounts of glucose and electrolytes are also commercially available [6]. The amount of protein in parenteral formulations is usually calculated relative to the amount of nonprotein calories required by each patient. Protein requirements range from 1 to 6 grams of protein/100 Kcal nonprotein energy in small animal patients [6]. In dogs, approximately 2 to 3 grams of protein/100 Kcal nonprotein calories should be administered on a daily basis. In cats, the value is slightly higher, at 4 g protein/100 Kcal [6]. In patients with hepatic or renal insufficiency, smaller amounts of protein should be provided; in patients with large amounts of protein loss, larger portions should be considered. Because most amino acid solutions do not contain the amino acid taurine, taurine supplementation should be considered if parenteral nutrition is required for long-term management of feline patients [2].

Lipids

Lipid emulsions are often a combination of soybean and safflower oil, and linoleic and linolenic acids [6]. Lipid sources for parenteral nutrition administration are available as 10 to 20% solutions, and are used to provide 40 to 60% of the patient's daily nonprotein calorie requirements [11]. Lipids traditionally supply essential fatty acids and provide a source of calories in an isotonic fluid. Because lipid emulsions typically have a lower osmolality (260 - 310 mOsm/L) [6,9,10] than amino acid solutions, lipids can be administered by peripheral catheters with minimal risk of causing thrombophlebitis.

Dextrose

Carbohydrate sources are typically provided as dextrose (2.5% - 70%) in parenteral nutrition formulations. Most commonly, 50% dextrose is combined with lipid and amino acid solutions for a patient's daily nutritional needs. The exact ratio of dextrose to lipid to meet a patient's caloric requirements is a topic of debate. During states of stressed starvation, glucocounterregulatory hormones such as cortisol and epinephrine promote a state of insulin resistance. The body is unable to utilize carbohydrate sources for energy, and hyperglycemia develops. In humans, hyperglycemia secondary to oversupplementation of carbohydrates has been shown to increase patient morbidity, respiratory failure, and mortality. In small animal patients, dextrose as provided in parenteral nutrition formulations should not exceed 50% of total daily caloric requirements.

Electrolytes

Electrolyte abnormalities are a common complication of critical illness and parenteral nutrition administration. The most common electrolyte abnormalities observed are hypokalemia and hyperphosphatemia. Following a period of prolonged anorexia and malnutrition, infusion of supplemental dextrose alone or in combination with amino acids and lipids can stimulate insulin release, driving glucose, potassium, and phosphorus intracellularly. Provision of nutrients and the production of high-energy-containing compounds such as adenosine triphosphate (ATP) can deplete a patient's phosphorus stores, resulting in hypophosphatemia. Measuring a patient's levels of potassium and phosphorus is necessary in order to determine the appropriate amount of potassium and phosphorus supplementation. In most cases, adding 20 to 40 mEq/L of potassium chloride, or a mixture of potassium chloride with potassium phosphate (0.01 - 0.03 mmol/kg/hour) may be necessary to maintain normokalemia and normophosphatemia. Ten milliliters of 10% calcium gluconate solution can be administered in each liter of parenteral nutrition [10].

Vitamins

Most patients do not require fat- and water-soluble vitamin supplementation unless the anorexia and weight loss have been prolonged or if nutrient absorption has been diminished because of excessive diarrhea or steatorrhea [6]. A weekly dose of Vitamin K1 (0.5 mg/kg) has been suggested at the onset of parenteral nutrition [2,6]. Other fat-soluble vitamins (A,D, and E) can be administered as a repository solution (1 ml IM, Schering-Plough Animal Healthcorp, Kenilworth, NJ) and will provide a sufficient store for approximately 3 months [6]. B-complex vitamins can be provided as a combination preparation in the parenteral solution (1 ml/100 Kcal or 3 ml/10 kg/day) [2]. Because some B-vitamins degrade when exposed to light, the parenteral nutrition solution should be covered to prevent degradation of labile substances.

Formulating Parenteral Nutrition Solutions

Before actually formulating a patient's daily parenteral nutrition, one must first calculate the daily energy requirements (resting energy expenditure, REE), then determine what percent of the REE will be provided as carbohydrate (dextrose) and what percent will be provided as lipid. Veterinary studies have documented that critically ill small animal patients actually require basal energy requirements [12], and are not "hypermetabolic" as previously suggested. A linear equation to calculate a patient's daily caloric requirements or resting energy expenditure (REE) is:
                REE = (30 x Body weight kg) + 70 = Kcal/day

Once the REE is calculated, the amount of calories provided by fat as lipid emulsion and of carbohydrate as dextrose is then calculated. Finally, the REE is divided by 100, to provide a multiplication factor for the amount of protein to add to the mixture. In order to determine the amount of each solution to add to the total mixture, one must know the concentration of lipid, dextrose, and amino acid in each component solution. The volume of each component is added together and the sum divided by 24 hours, to yield a rate of ml/hour to administer the parenteral nutrition. An example of step-by-step calculation of parenteral nutrition formula for a canine and a feline patient is located in Table 7-2. Once a bag of parenteral nutrition has been formulated, it can be refrigerated for up to 48 hours. The parenteral nutrition should be administered at room temperature. Each bag should be administered over a period of 24 hours, then discarded.

Total Nutrient Admixture

A simple method of providing the patient's total daily nutritional and fluid requirements is to combine the parenteral nutrition within a Lactated Ringer's or other isotonic fluid (Normosol-R, Plasmalyte-A) bag. First, the volume of each parenteral nutrition component is determined. Next, the patient's total daily fluid requirement is determined. The volume of the parenteral nutrition is adjusted to meet the patient's daily fluid requirements by adding an isotonic fluid such as Lactated Ringer's, Plasmalyte-M, or Normosol-R into the bag of parenteral nutrition. The additions are made in a sterile manner, then the fluid is infused into a dedicated line. The advantages of administering a TNA solution are that the patient requires just one dedicated catheter, one fluid administration set, and one fluid pump [4].

Central Catheter Placement

Infusion of a hyperosmolar substance into a peripheral vein is often associated with the development of thrombophlebitis. It is recommended, therefore, that parenteral nutrition solutions with an osmolality greater than 600 mOsm/L should be infused into a central venous catheter. In small animal patients, central venous catheters can be placed into the jugular, medial saphenous, and lateral saphenous veins with relative ease. Several single- and multiple-lumen catheter types are available. Polyurethane and silicone catheters are less irritating to the vessels and, therefore, are recommended over Teflon catheters [6]. A complete description of through-the needle and over-the-wire catheter placement is beyond the scope of this text. One of the most important concepts to remember when placing a central venous catheter is to maintain sterility at all times, to prevent catheter-related sepsis. First, the fur over the proposed site of catheter insertion should be clipped. Next, the clipped area should be aseptically scrubbed as with any surgical site. The area should be draped with sterile field towels to avoid contamination of the site. Wearing gloves, the practitioner can insert the catheter according to manufacturer's instructions, then secure it in place. The catheter entrance site should be covered with an antimicrobial ointment, then bandaged. The bandage should be labeled with the time and date of catheter placement, initials of the person who placed the catheter, and the date of bandaging. Once the catheter has been successfully placed and bandaged, the parenteral nutrition can be connected. The line should be labeled as a dedicated line and not be used for any purpose other than administration of the nutritional support. The line should not be disconnected for any reason except to change fluid/nutrition bags every 24 hours, even when taking the patient for a walk outside. The bandage should be changed and the catheter entrance site examined every 24 hours. Signs of phlebitis include erythema and pain at the catheter site, pain upon infusion into the vessel, and ropiness or hardening of the vessel on external palpation. In several retrospective studies regarding the use of central venous catheters for infusion of parenteral nutrition, catheter occlusion and kinking were among the most common complications observed [13,14,15].

Partial Parenteral Nutrition

Partial parenteral nutrition is the provision of a portion of a patient's daily nutritional requirements. Partial parenteral nutrition should be used only in cases where nutritional support is anticipated for less than 5 days, or during a transition period when a patient is consuming only a portion of the daily nutritional requirements enterally. The osmolality of partial parenteral nutrition formulations is usually lower than 600 mOsm/L, and therefore, they can be administered through a peripheral vein. Because amino acid solutions are hyperosmolar, peripheral parenteral solutions typically contain small amounts of amino acid and provide a portion of the patient's caloric requirements as a mixture of dextrose and isoosmolar lipid solutions. Because of volume and osmolality constraints, peripheral parenteral nutrition only provides a portion of a patient's daily nutrient needs [13,16].

Complications of Parenteral Nutrition

One of the most common reasons for not implementing parenteral nutritional support in critically ill veterinary patients is the perception of numerous complications. Several studies have been published investigating the use of parenteral nutrition in veterinary patients. Complications associated with parenteral nutrition administration can be categorized as mechanical, metabolic, or septic (Table 7-3) [3,13]. Mechanical complications are most common and are typically associated with catheter dislodgement, kinks, and clogging [3,13-15]. Metabolic complications include transient hyperglycemia, hypokalemia, hyperlipidemia, hypophosphatemia, hyperbilirubinemia, hyponatremia, and hypochloremia [3,13-15]. In one study [14], hyperglycemia at 24 hours after onset of PN infusion was associated with increased risk of mortality. In human patients, persistent hyperglycemia can contribute to respiratory fatigue and increased patient mortality. Administration of 10 units of regular insulin per liter of parenteral nutrition can decrease the hyperglycemia associated with PN administration [3].

Lack of enteral nutrition can promote disuse atrophy of enterocytes and promote bacterial translocation and sepsis. In several veterinary studies, septic complications during administration of parenteral nutrition were few and were associated with the patient's primary disease process or to disruption of the patient's designated infusion line [3,13-15].

Conclusions

Parenteral nutrition should be considered in any patient that cannot tolerate enteral feeding. Nutritional plans should be formulated based on individual patient requirements, disease processes, anticipated length of required nutritional support, and risk of complications. The risks of increased patient morbidity and mortality and of delayed wound healing greatly exceed the perceived risks of increased patient expense and mechanical, metabolic, or septic complications. With increased use and technical proficiency, placement of dedicated central venous catheters and administration of parenteral nutrition can become commonplace in all veterinary hospitals, provided that aseptic techniques are strictly adhered to.