V CE
20TH ANNIVERSARY
Vol. 21, No. 6 June 1999
Refereed Peer Review
FOCAL POINT ★Peripheral parenteral nutrition (PPN) is a safe, simple technique that can be used as an alternative to total parenteral nutrition (TPN) in selected patients.
KEY FACTS ■ Abolishing protein catabolism is impossible in many ill or traumatized patients, but nutritional support helps minimize losses and supports the patient until recovery. ■ Administering PPN is a simpler method of providing nutritional support compared with TPN and usually is associated with fewer complications. ■ Although combination parenteral products are commercially available, compounded PPN formulas are superior because they provide more balanced nutrition and can be tailored to meet individual patients’ needs. ■ Strict adherence to administration, monitoring, and aseptic technique protocols in patients receiving PPN will reduce the risk of complications.
Peripheral Parenteral Nutrition Tufts University
Erika Zsombor-Murray, DVM Lisa M. Freeman, DVM, PhD ABSTRACT: Many clients now expect appropriate nutritional support to be provided to their hospitalized pets. In many veterinary clinics, enteral nutrition via feeding tubes is perceived to be the only viable option. Although enteral nutrition is usually the preferred method, parenteral nutrition is the method of choice when the enteral route is contraindicated. Advances in the formulation of parenteral nutritional solutions, intravenous catheters, and administration techniques make its use more amenable to veterinary clinics. Parenteral nutrition administered through a peripheral vein can be used as an alternative to total parenteral nutrition in appropriate patients.
M
etabolic alterations put ill and traumatized patients at risk for malnutrition and its deleterious effects on immune function, wound healing, and overall survival.1 The benefits of nutritional support in preventing malnutrition are well accepted, but the optimal use of parenteral or intravenous nutrition is controversial. In the past, parenteral nutrition was recommended only when enteral nutrition was contraindicated; parenteral nutrition was sometimes considered a technique that should be avoided at all costs because of its potential complications. Administering parenteral nutrition has also been presented as a complicated prospect for nutritional support. Thus, its use in veterinary medicine has been primarily limited to universities and a few referral hospitals. However, parenteral nutrition is now more accepted, safer, and easier than it once was, and its use is becoming more feasible for all veterinarians. Much of the initial resistance to parenteral nutrition was the result of its potential complications, some of which can be overcome or minimized by using the peripheral route of administration.
HISTORY OF PARENTERAL NUTRITION The use of parenteral nutrition in companion animals is not new. In 1656, a pig’s bladder attached to a goose quill was used to infuse wine into a dog’s vein.2 In the 1930s, increased study and awareness of the dangers of malnutrition provided the impetus behind the development of better methods to prevent it. Parenteral nutrition began to be used in the late 1930s to prevent and treat malnutrition in humans; however, its regular use in humans did not occur until the late 1960s, at which time Dudrick and coworkers reported normal growth and development in dogs fed parenterally.3 The use of parenteral nutrition in dogs was first reported in the veterinary literature in 1977 in an article on the success-
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20TH ANNIVERSARY
ful maintenance of 10 dogs for up to 1 month using total parenteral nutrition (TPN).4 Since that time, the use of parenteral nutrition in ill animals has expanded. Initially, parenteral nutrition was provided through a large central vein (e.g., subclavian vein in humans, jugular vein in dogs and cats). The risks associated with central venous catheters (e.g., sepsis, complications during placement) may delay initiation of TPN support or prevent its use completely. Therefore, techniques that simplify initiation and administration of parenteral nutrition and reduce the risk of complications make its use more feasible. One way of achieving these goals is by administering parenteral nutrition peripherally, which has become possible because of the development of new nutritional products and changing ideas of the goals of parenteral nutrition.
GOALS OF PARENTERAL NUTRITION The goals of parenteral nutrition are no different than those of any other type of nutritional support—to prevent nutritional deficiencies by providing adequate energy substrates, protein, and micronutrients. During the hypercatabolic state in ill animals, there is accelerated loss of lean body mass; ongoing protein catabolism and wasting of lean body mass cannot be abolished with nutritional support.5 The goal of nutritional support in these patients, therefore, is to support the patient and minimize ongoing destruction of body tissue until the animal recovers. This requires the provision of adequate calories and protein. It is now accepted that providing excessive levels of calories and protein will not improve a patient’s condition and is likely to cause complications. Another goal of nutritional support is to prevent vitamin and trace-element deficiencies. Currently available solutions for parenteral nutrition are designed for humans and do not meet all the amino acid, vitamin, or trace-element requirements for dogs or cats, prompting some veterinary nutritionists to avoid the term “total” parenteral nutrition. Nonetheless, parenteral nutrition has successfully supported dogs and cats for months and is thus usually sufficient for our purposes.3,4 Parenteral nutrition solutions that meet the specific requirements of our patients, however, will require further research and development. Ideas regarding the nutritional requirements of patients have changed over the past decade. Not only must basic nutritional requirements be met, but certain nutrients called conditionally essential nutrients (e.g., the amino acid glutamine) may be required in higher than normal amounts in ill or traumatized patients. In addition, some nutrients may have benefits when provided at concentrations higher than those needed for
Small Animal/Exotics
known nutritional requirements. This higher concentration is meant to improve immunity, diminish the chance of gut-derived sepsis, or hasten wound healing.6 Using nutrients in this manner is known as nutritional pharmacology. Examples of nutrients that have been used experimentally include arginine, zinc, and n-3 polyunsaturated fatty acids. In the future, our knowledge may be sufficiently sophisticated to formulate a nutritional protocol not only based on a patient’s caloric, protein, and micronutrient requirements but also aimed at modulating the deleterious effects of the disease itself.
INDICATIONS Parenteral Nutrition Nutritional support is indicated in patients that are malnourished; unlikely to eat for more than 3 days; or at risk of developing malnutrition because of profound, ongoing protein losses. The enteral route still should be the first choice for providing nutritional support and should be used when possible. Enteral feeding is a safer, more economical, and more convenient method of providing nutrition. In addition, providing nutrition by the enteral route has specific benefits to the gastrointestinal tract by preventing mucosal atrophy, maintaining local immunocompetence, and preserving normal flora.7 Despite these advantages, there are situations in which the parenteral route should be chosen. Parenteral nutrition should be selected when enteral nutrition cannot be tolerated, such as in patients with vomiting or regurgitation, those with severe malabsorption or gastrointestinal obstruction, and potentially in patients that cannot protect their airway. Parenteral nutrition can also be used to supplement enteral feedings in patients that cannot tolerate receiving all nutritional requirements enterally. Theoretically, providing even a small amount of nutrition enterally in conjunction with parenteral nutrition could help improve patient outcome by protecting mucosal integrity and minimizing the potential for bacterial translocation and sepsis. Parenteral nutrition can be provided via a large central vein or a peripheral vein and can provide either 100% of requirements or partial-energy requirements. There is currently much controversy regarding the nomenclature of parenteral nutrition in both the veterinary and human literature. We define TPN as a parenteral solution formulated to provide 100% of energy requirements and administered as a hyperosmolar solution via a central vein. Peripheral parenteral nutrition (PPN), sometimes also called partial parenteral nutrition, is defined here as a parenteral solution formulated to provide 50% of energy requirements and administered via a peripheral vein. TPN is a combination of dextrose and amino acids with or
TOTAL PARENTERAL NUTRITION ■ CONDITIONALLY ESSENTIAL NUTRIENTS ■ NUTRITIONAL PHARMACOLOGY
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Compendium June 1999
without a lipid source, vitavolumes can be adminismins, and trace elements. tered. In addition, solutions The use of TPN has been reavailable in the past were viewed. 8–10 Because of the too high in osmolarity to be technical requirements of TPN administered peripherally. It administration and potential was not until the developcomplications, however, its ment of safe fat emulsions use is not always feasible. that PPN became a reality. Nevertheless, there are many Fats are a more concentrated animals that can benefit from energy source than is gluparenteral nutrition, and thus cose and reduce the osmoPPN may be a practical alterlarity of PPN solutions.11 Providing parenteral nutrinative. Peripheral parenteral nu- Figure 1—In certain patients, parenteral nutrition adminis- tion via a peripheral catheter trition is an option that may tered through a peripheral vein can be an effective and simple offers several advantages over alternative to total parenteral nutrition. using a central catheter (see be easier to implement than Advantages of Peripheral Paris TPN (Figure 1). The forenteral Nutrition). The first is the ease of peripheral mula presented in this article provides a solution with a catheter placement compared with placing jugular lower osmolarity than that of TPN that can still procatheters. In many hospitals, technicians do not routinely vide 50% of caloric needs. There are other methods of place jugular catheters and TPN is therefore not an opformulating PPN solutions that allow up to 100% of tion. Another advantage is that PPN is less likely than is caloric requirements to be met, but calculating and administering these formulas can be more challenging. The formula for PPN presented in Candidates for Peripheral Parenteral Nutrition this article is easy to administer and results in few complications when specified protocols are ■ Patients in which the support (i.e., fewer than 5 followed, thus requiring less intensive monitorgastrointestinal tract to 7 days) ing than that required for TPN. cannot be used (e.g., due to obstruction, severe malabsorption, pancreatitis, or risk of aspiration) ■ Nondebilitated patients ■ Patients likely to require only short-term intravenous nutritional
Peripheral Parenteral Nutrition Peripheral parenteral nutrition has a number of advantages over TPN. It should not, however, be viewed as a replacement for TPN but as an alternative that may be appropriate in selected patients (see Candidates for Peripheral Parenteral Nutrition). Because PPN will not provide all of an animal’s energy requirements, it should not be used in patients that are debilitated (i.e., those that already have signs of malnutrition), have large protein losses, or will require nutritional support for long periods. ADVANTAGES AND DISADVANTAGES OF PERIPHERAL PARENTERAL NUTRITION It is only within the past decade that PPN has been considered a reasonable route of administration for parenteral nutrition. Previously, parenteral nutrition was administered only via a large central vein because relatively large volumes of parenteral nutrition were given to most patients to meet perceived energy requirements. Estimates of energy requirements are now much more conservative; thus smaller
■ Patients in which a jugular catheter cannot be placed ■ Patients that cannot tolerate their full nutritional requirements enterally (use peripheral parenteral nutrition to supplement oral or tube feeding [lowdose enteral nutrition])
Advantages of Peripheral Parenteral Nutritiona ■ Easier catheter placement ■ Less likely to cause metabolic complications ■ Less intensive monitoring is required a
■ Nutritional support may be initiated earlier ■ Can be as effective as total parenteral nutrition in appropriately selected patients
Versus total parenteral nutrition.
INDICATIONS FOR PPN ■ ENERGY REQUIREMENTS ■ FAT EMULSIONS
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20TH ANNIVERSARY
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TPN to cause metabolic anced nutrition and are probReducing Thrombophlebitis Risk in complications because of its lematic when used alone (e.g., Patients Receiving Peripheral lower energy content. This 50% dextrose is too hyperosParenteral Nutrition (PPN)14–16 means that clinicians may be molar and 5% dextrose is more likely to initiate nutritoo low in calories to be ben■ Use the largest vein and smallest catheter tional support earlier, resulteficial when administered possible. ing in a shorter delay to the alone via a peripheral vein; ■ Use a catheter material of the lowest onset of therapy. In addition, Table I). For example, adless intensive monitoring is ministering 5% dextrose to a thrombogenicity (polyurethane or silicone is required. Finally, in appropri25-lb dog at a maintenance ideal; tetrafluoroethylene is acceptable; avoid ately selected patients, PPN fluid rate would provide only polyvinyl chloride and polyethylene). can be as effective as TPN. 128 kcal (less than 25% of ■ Keep the osmolarity of the solution below 750 Human studies show similar energy requirements and no mOsm/L. muscle and respiratory funcprotein). Administering lipid ■ Use three-in-one solutions containing lipid to tion with TPN and PPN in as a single agent can suppress postoperative patients.12 Simthe immune system and, like reduce osmolarity. ilarly, nondebilitated dogs dextrose, provides no pro■ Keep the pH of the solution neutral. and cats with pancreatitis tein. The osmolarity of amino ■ Administer PPN through a 1.2-µm inline filter. maintained body weight acids (Table I) makes this so■ Follow protocols for compounding and while receiving PPN.13 lution too irritating to the administering solutions and monitoring patients The primary disadvantage vascular endothelium to be receiving PPN. of PPN is the limited numadministered peripherally, ber of calories that can be and amino acids are not a ■ At the first signs of thrombophlebitis, remove the provided peripherally. Thus, balanced or efficient means catheter and place a new one at a different site. an animal receiving PPN of providing calories. Thus, can still become malnourthe use of these agents indiished. If the patient’s underlying condition does not vidually as a means of nutritional support should be improve after 3 to 5 days of PPN, other methods of avoided. nutritional support should be used (i.e., a combinaCommercial Combination Products tion of enteral nutrition and PPN; TPN if the animal Until recently, there were no commercially available cannot tolerate enteral feeding). Although PPN will dextrose–amino acid solutions because such solutions help to maintain nutritional status, it will not imwere difficult to sterilize. When heat-sterilized together, prove nutritional status in an already debilitated paamino acids and dextrose undergo the Maillard browntient; therefore, its use should be restricted to nondeing reaction, which adversely affects the quality of the bilitated animals. individual ingredients. Thus, manufacturers had to deIn humans, thrombophlebitis continues to be the most vise alternate methods for this process. common problem associated with PPN administration. There are two approaches to this problem. Dextrose The incidence of thrombophlebitis in human patients and amino acids can be sterilized in a dual-chamber ranges from 2.3% to 70%, depending on the study14; the incidence in dogs and cats has not been reported but bag in which the two components are connected but anecdotally appears to be lower than that in humans. separated (Figure 2). Just before administration, the seal Nonetheless, many factors increase the risk of thrombetween the two compartments is broken by squeezing bophlebitis, including properties of the veins, catheter, the bag and the solutions are mixed. Products that use and solution as well as infusion rates, all of which must this approach are Clinimix™ and Quick Mix® (both manufactured by Clintec Nutrition Co., Deerfield, IL; be considered to maintain a low incidence of this probTable I). In another product (ProcalAmine®; McGaw, lem (see Reducing Thrombophlebitis Risk in Patients 14–16 ). Inc., Irvine, CA), glycerin or glycerol, which can safely Receiving Peripheral Parenteral Nutrition be sterilized with amino acids, is used as a calorie PERIPHERAL PARENTERAL NUTRITION source. Glycerol can be a substrate for glycolysis and is SOLUTION CHOICES thus an effective substitute for glucose. In addition, less Single Agents exogenous insulin is required in humans to maintain Although single agents are available and have been glucose homeostasis with a glycerol-containing solution used clinically by veterinarians, they do not provide balcompared with an isocaloric, isonitrogenous dextrose– THROMBOPHLEBITIS ■ DEXTROSE–AMINO ACID SOLUTIONS ■ GLYCEROL
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Compendium June 1999
TABLE I Commercially Available Components Versus Combination Solutions for Peripheral Parenteral Nutritiona Trade Osmolarity Na+ Cl + K+ Mg ++ Ca ++ PO4 – – Calories (kcal/L) Name (mOsm/L) pH (mEq/L) (mEq/L) (mEq/L) (mEq/L) (mmol/L) (kcal/L) Nonprotein Protein
Components 5% dextrose
––
252
4.0
––
––
––
––
––
––-
170
––
10% dextrose
––
505
4.0
—
—
—
—
—
—
340
—
50% dextrose
—
2525
4.2
—
—
—
—
—
—
1700
—
8.5% amino acids
Travasol®
890
6.0
—
34
—
—
—
—
—
340
8.5% amino acids with electrolytes
Travasol®
1144
6.0
70
70
60
10
—
30
—
340
20% lipid
Intralipid®
260
8.0
—
—
—
—
—
15
2000
—
10% lipid
Intralipid®
260
8.0
—
—
—
—
—
15
1000
—
Combination Products 2.75% amino Clinimix™ b acids/5% dextrose (2 L)
665
6.0
35
39
30
5
4.5
15
170
110
670
6.0
35
35
30
5
—
15
170
110
3% amino acids/3% ProcalAmine® 735 glycerin (1 L)
6.8
35
41
24
5
3
3.5
130
116
2.75% amino acids/5% dextroseb
Quick Mix® (1 L)
aRepresentative
products are listed; see text for manufacturer information. Similar available products may have different properties. without electrolytes are also available. Ca = calcium; Cl = chloride; K = potassium; Mg = magnesium; Na = sodium; PO4 = phosphate. b Products
amino acid combination.17 The number of calories provided is less than that in the dextrose–amino acid products (Table I). The major advantages of using these products are their commercial availability and the fact that no preparation is required. This makes them useful in clinics that are not yet equipped to mix PPN solutions. These products vary in their osmolarity, protein content, caloric density, pH, and electrolyte concentration (Table I), and thus it is important to determine which is most appropriate for an individual patient. Potassium content in these products ranges from 24 to 30 mEq/L; therefore, additional potassium supplementation is usually not required unless a patient is severely hypokalemic. Additional sodium and chloride supplementation may be required if ongoing losses or preexisting imbalances are present. It also is important to realize that the amino acid profiles are designed for humans and do not necessarily meet canine or feline re-
quirements. We currently administer these products at a maintenance fluid rate (cats, 50 ml/kg/day; dogs, 66 ml/kg/day) by continuous-rate infusion unless this rate is contraindicated (e.g., in cardiac disease). At this rate, these products provide the majority of protein requirements (dogs, 100%; cats, 50% to 60%) but only 20% to 40% of an animal’s energy requirements and should be used only in nondebilitated patients. Benefits of these commercial solutions are attributed to the concept of “protein-sparing,” which is the idea that administering the products will decrease the use of endogenous protein. In some studies, using combination products improved nitrogen balance compared with amino acids or dextrose alone, although the benefits of protein-sparing are still controversial.18 Some advocate the use of lipid solutions in conjunction with these commercial products to supplement caloric intake. Lipids can be administered through a Y-type administration set, although this increases the risk of sepsis.
SODIUM AND CHLORIDE SUPPLEMENTATION ■ AMINO ACID PROFILES ■ PROTEIN-SPARING
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Lipids Although dextrose and amino acid solutions supply readily usable sources of calories and protein, respectively, they have the disadvantage of significantly increasing the tonicity of the solution as their concentrations rise and are thus more thrombogenic. Providing PPN with only dextrose and amino acids therefore carries a high risk of thrombophlebitis (if 50% dextrose is used) or provides negligible calories (if 5% or 10% dextrose is used). Thus, it was only after safe lipid emulsions were developed for commercial use that PPN became practical. Lipids are an ideal nonprotein calorie source because of their much higher energy content (9 kcal/g for lipids Figure 2—One type of commercially compared with 4 kcal/g for protein or available combination product for peThree-in-One Formula carbohydrate), low osmolarity, and ripheral parenteral nutrition adminisThe preferred method for supplying tration combines dextrose and amino neutral pH. Intralipid® (Clintec NutriPPN is to compound a mixture specif- acids in a dual-chamber bag. tion Co.) is currently the most comically tailored to the patient’s individumonly used lipid source in the United al needs using amino acids, dextrose, States. It is available in a 10% or 20% and lipid. The formulation should have an osmolarity solution (Table I); a maximum infusion rate of 2 that is less than 750 mOsm/L. g/kg/day should be observed. Intralipid® contains fat from soybean oil and egg yolk phospholipid in combiAmino Acids nation with glycerol to create an isotonic solution. UsA variety of amino acid solutions are available, ining lipids in compounded PPN solutions allows the cluding standard preparations and specialized soluformulation of peripheral solutions that provide a reations designed for humans with various diseases (e.g., sonable number of calories without increasing the risk formulas for hepatic or renal disease). The safety and of thrombophlebitis.11 The diminished incidence of efficacy of these specialized solutions have not been thrombophlebitis in humans who are given lipid-contested in dogs or cats, and their cost usually makes taining solutions may also be attributed to a “coating” them unrealistic for veterinary use. Therefore, this areffect of lipid emulsions.19 ticle discusses only standard amino acid preparations. Several precautions must be undertaken when using The most commonly used amino acid preparation lipid solutions. Because lipid solutions may react with (Travasol®; Clintec Nutrition Co.) consists of 8.5% other PPN ingredients, careful observation for discolamino acids in sterile water and provides 340 kcal/L oration or precipitation during mixing is necessary. In and essential amino acids for humans (Table I). addition, fat precipitates can form and cause fat emAmino acids are available with or without elecbolization in animals. Side effects to lipid solutions are trolytes, and the appropriate selection depends on the rare, but chills, fever, and headaches occasionally occur status of the individual patient. All compounded in humans.11 Anecdotal reports in dogs and cats suggest PPN solutions should contain amino acids as a prothat allergic reactions, such as rashes, can develop from tein source. repeated lipid infusion. Propofol has the same base as lipid solutions; thus allergic reactions could theoreticalDextrose ly develop in animals that have received propofol. High Dextrose is used as a caloric source for PPN. Three dosages or rapid infusion of lipid solutions suppress the preparations (50%, 10%, and 5%) are available, but reticuloendothelial system and can therefore impair imonly the 5% or 10% preparations should be used for mune function.20 Finally, lipid solutions are normally peripheral administration because of their osmolarity quickly cleared from the serum, but patients with cer(see Table I for comparison). tain diseases (e.g., hypothyroidism, idiopathic hyperMost animals tolerate the administration of combination products well, although some with moderate to severe hepatic or renal failure may not tolerate their administration at the usual rate; these animals may require more cautious administration or different nutritional support techniques. Care should be taken when administering these solutions to cardiac patients because of their sodium content and the potential for fluid overload. Thrombophlebitis can occur because of the relatively high osmolarity. Although these commercial products are superior to any single agent for nutritional support, they are not a replacement for other types of parenteral nutrition and are used only for interim support in our hospital.
PROTEIN SOURCE ■ CALORIC SOURCE ■ LIPID PRECAUTIONS
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lipidemia, pancreatitis) have abnormalities in lipid clearance and may not tolerate the use of lipid in PPN.11 Lipids should not be used in animals with preexisting hypertriglyceridemia or should at least be used at reduced concentrations and with caution.
Vitamins and Trace Minerals In our hospital, vitamins are routinely added to compounded PPN solutions. Although there has been a nationwide shortage of parenteral vitamins for both humans and companion animals, one company currently has an available parenteral multivitamin preparation (Cernevit™; Clintec Nutrition Co.) that contains vitamins A, D, E, C, and B; biotin; and folate. Our hospital uses a dose of 0.5 ml reconstituted product/5 kg body weight (maximum, 5 ml/animal). An alternative is to use a standard parenteral B-vitamin complex solution for animals (2 ml/L of PPN). Trace elements (zinc, copper, manganese, and chromium) can also be administered, although we consider these to be optional in most patients receiving PPN because they should already be well nourished. When used, trace elements (Abbott Laboratories, North Chicago, IL) are administered at a dose of 0.5 ml/5 kg body weight (maximum, 5 ml/animal). CALCULATING REQUIREMENTS AND A PERIPHERAL PARENTERAL NUTRITION FORMULA In our hospital, commercial PPN solutions are used as an interim means of nutritional support (i.e., for 1 to 2 days) and are administered at a maintenance fluid rate (cats, 50 ml/kg/day; dogs, 66 ml/kg/day). Veterinary nutritionists use a variety of methods for formulating three-in-one PPN, and each has its advantages and disadvantages. This article presents the technique used in our hospital (see Worksheet for Calculating Three-in-One Compounded Peripheral Parenteral Nutrition), although it is important to note that this is not the only method possible and that it provides only 50% of energy requirements (plus 100% and 50% to 60% of protein requirements in dogs and cats, respectively). The method is designed to approximate a maintenance fluid rate and has been used successfully in more than 200 dogs and cats in our hospital. First, the animal’s energy requirements are calculated. The resting energy requirement (RER) is the number of calories required for maintaining homeostasis while an animal sits quietly. The most accurate formula for calculating RER is: RER = 70 × Body weight0.75 (kg) For animals that weigh between 2 and 35 kg, the following linear formula gives a good approximation of energy needs:
Compendium June 1999
RER = 30 × Body weight (kg) + 70 The second step for determining energy requirements is to calculate the illness energy requirement (IER), which is an estimate of the number of calories needed to sustain an ill or injured patient. This is calculated by multiplying the RER by an illness factor, which is a subjective assessment of a patient’s needs above those required for RER. Illness factors for dogs and cats have been extrapolated from research in human patients and are selected based on activity level and underlying disease.10 Until recently, illness factors as high as 2.0 were used in human and veterinary patients to calculate IER, but these values were too high and often led to overfeeding. Current recommendations in both humans and animals are therefore more conservative, and illness factors lower than 1.5 should be used for nearly all patients. Therefore, the IER is calculated as follows: IER = RER × Illness factor (i.e., 1.0 to 1.5) Next, the partial energy requirement (PER) is calculated. Because only 50% of the animal’s IER can be provided by three-in-one PPN, the IER is multiplied by 50%. Depending on the size of the animal, different percentages of the PER are supplied by dextrose, amino acids, and lipid. These are standard formulas, and percentages may need to be adjusted depending on the animal’s underlying disease. For example, if the animal has preexisting hypertriglyceridemia, reduction or elimination of the lipid is necessary. Commercial parenteral multivitamins for humans are routinely added to PPN in our hospital, although a standard parenteral B-vitamin complex can also be used. Trace elements also can be administered if desired. Vitamin K is administered subcutaneously once on day 1 of PPN and then once weekly. If amino acids with electrolytes are used, this formulation will approximate maintenance amounts of potassium. Additional potassium supplementation may be required if hypokalemia is present.21 Other supplements, including drugs, may or may not be compatible with the PPN. Check with the manufacturer of the supplement before adding anything to the PPN. Any additives should be introduced in a sterile fashion at the time of mixing.
SOURCES OF PERIPHERAL PARENTERAL NUTRITION COMPOUNDING Some clinics have the facilities and technical staff to compound their own PPN. This requires a clean area, adequate supplies, and trained personnel. Commercial sets are available for compounding PPN (i.e., sterile bags with three-lead transfer sets [All-in-One Containers; Clintec Nutrition Co.]; Figure 3) that can be connected
RESTING ENERGY REQUIREMENT ■ ILLNESS ENERGY REQUIREMENT ■ PARTIAL ENERGY REQUIREMENT
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Compendium June 1999
Worksheet for Calculating Three-in-One Compounded Peripheral Parenteral Nutrition (PPN) Resting Energy Requirement (RER) RER (kcal/day) = 70 × Body weight0.75 (kg) or, for animals weighing between 2 and 35 kg: RER = 30 × Body weight (kg) + 70 = kcal/day
RER = _____ kcal/day
Illness Energy Requirement (IER) IER = RER × Illness factor
IER = _____ kcal/day
Partial Energy Requirement (PER) To supply 50% of the animal’s IER PER = IER × 0.50
PER = _____ kcal/day
Nutrient Requirements (Note: This will supply fluids at greater than maintenance rate for animals <3 kg) Cats and dogs <10 kg: PER × 0.25 = _____ kcal/day from dextrose PER × 0.25 = _____ kcal/day from amino acids PER × 0.50 = _____ kcal/day from lipid
Dogs 10 to 25 kg: PER × 0.33 = _____ kcal/day from dextrose PER × 0.33 = _____ kcal/day from amino acids PER × 0.33 = _____ kcal/day from lipid
Dogs >25 kg: PER × 0.50 = _____ kcal/day from dextrose PER × 0.25 = _____ kcal/day from amino acids PER × 0.25 = _____ kcal/day from lipid Nutrient Solution Volume Requirements 5% dextrose = 0.17 kcal/ml
_____ kcal/day from dextrose ÷ 0.17 kcal/ml = _____ ml/day
8.5% amino acids with electrolytes = 0.34 kcal/ml
_____ kcal/day from amino acids ÷ 0.34 kcal/ml = _____ ml/day
20% lipid solution = 2.00 kcal/ml
_____ kcal/day from lipid ÷ 2.00 kcal/ml = _____ ml/day
Micronutrient Requirements Multivitamins (Cernevit™; Clintec Nutrition Co., Deerfield, IL) Add 0.5 ml reconstituted product/5 kg of body weight (up to 5 ml/day) = ______ ml/day Standard parenteral B-vitamin complex (2 ml/L) can also be used. Trace elements (Abbott Laboratories, North Chicago, IL)—Optional Add 0.5 ml/5 kg (up to 5 ml/day) = ______ ml/day Vitamin K Administer 0.5 mg/kg subcutaneously once on day 1 of PPN and then once weekly For animals <25 kg, this formulation will approximate maintenance amounts of potassium. For animals >25 kg, additional potassium supplementation may be required, depending on serum potassium concentrations.
Total Requirements _____ ml 5% dextrose _____ ml 8.5% amino acids with electrolytes _____ ml 20% lipid solution _____ ml multivitamin solution + _____ ml trace-element solution _______________________________________ = _____ ml total volume of PPN solution Administration Rate Total volume of PPN solution ____ ml ÷ 24 hr = _____ ml/hr This formulation approximates a maintenance fluid rate. Check that this rate is appropriate for the patient and that other fluids are adjusted accordingly.
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20TH ANNIVERSARY
to dextrose, amino acids, and lipid for transfer to a special mixing bag. After mixing, the bag is clamped off and the solution is administered to the animal. For many clinics, however, compounding PPN in-house is not feasible. In this situation, there are now a number of alternatives. Many pharmacies in human hospitals are willing to make arrangements with veterinarians to compound PPN. Typically, they require the calculations to be made by the veterinarian, and either one or several days’ worth of PPN is compounded (it is often more cost efficient to make enough for several days at a time). Alternatively, some universities and referral veterinary clinics will compound PPN and ship it to veterinarians. The advent of human home health care in many cities has recently expanded the availability of TPN and PPN for veterinarians. Many home health care companies compound and deliver TPN to human patients on a daily basis and are willing to make arrangements with veterinarians for this service. Using the method of calculation described in this article, PPN can now be available to most veterinary clinics.
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more likely to result in metabolic complications (see Complications and Monitoring section). Using the calculations in this article, PPN can be started at the full calculated rate (i.e., there is no need to gradually increase the PPN rate). Bags of PPN should be refrigerated until used and hung at room temperature for no longer than 24 hours. A bag of PPN should not be administered to more than one animal. An animal’s tolerance of oral feeding and its condition should be assessed daily. If the animal’s condition does not start to resolve after 3 to 5 days of PPN administration, either TPN or PPN combined with enteral nutrition should be considered. When the animal is able to acquire at least half of its energy requirements orally, PPN can be Figure 3— A sterile bag with a three-lead discontinued (tapering PPN is not retransfer set allows veterinary clinics to com- quired). pound a three-in-one peripheral parenteral Inline filters (1.2 µm) should alnutrition in a sterile fashion. ways be used as part of the administration set to filter particulate matter from the solution and to prevent air from entering the vascular system. Solutions should be administered with an infusion pump to avoid giving a bolus of the PPN solution. A nonthrombogenic catheter should be placed; we use 8- to 12PERIPHERAL PARENTERAL inch, 19- to 22-gauge, tetrafluoNUTRITION ADMINISTRATION roethylene Intracath ® catheters Regardless of the type of PPN (Becton Dickinson, Sandy, UT). chosen, there are certain rules of adMaintaining the sterility of PPN ministration that apply. Dehydrated solutions, lines, and catheters is abpatients should be rehydrated besolutely critical to prevent sepsis fore commencing PPN administrabecause the solution is an ideal tion. Ongoing fluid losses should be growth medium for bacteria. corrected with concurrent adminisThe patient’s PPN catheter tration of a crystalloid fluid. Thus if Figure 4—Catheters and lines used for pe- should be a dedicated line and ongoing fluid losses are miscalculat- ripheral parenteral nutrition administration should therefore not be used to aded or change daily, adjustments to must be handled aseptically to reduce the minister medications or additional risk of infection. the crystalloid fluid therapy can be fluids, take blood samples, or meaperformed without altering the PPN sure central venous pressure. The solution or rate of administration. The PPN solution line should not be disconnected, except to change PPN itself is calculated to approximate maintenance fluid rebags. When the bag is empty (which should occur every quirements. Ideally, PPN should be administered over 24 hours), the bag, line, and catheter bandage should be 24 hours as opposed to cyclically. In certain conditions, changed. Sterile technique should be used when hansuch as a hospital without 24-hour care, it may be acdling the catheter or the line and when changing bags ceptable to administer PPN over 12 hours, but this is (Figure 4). The catheter site should be evaluated for COMPOUNDING PPN ■ INLINE FILTERS ■ BAGS AND CATHETERS
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signs of swelling, redness, or irritation. If there is irritation at the site or any question of the catheter’s patency, the catheter should be removed and a new one placed in a different vein. The catheter should be carefully rewrapped. The bandage also should be changed if it becomes soiled with urine, feces, or vomit.
S M’
COMPLICATIONS AND MONITORING Although complications are much less common with PPN than with TPN, patient monitoring is still one of the most important aspects of providing nutritional support. Potential complications can be mechanical, metabolic, or septic. ENDIU The most common comP M plications of PPN are mechanical, including catheter ANNIVERSARY occlusion or premature removal, line disconnection or breakage, and thrombophlebitis. Catheter and line problems can be miniThe importance of providing mized by careful attention nutrition to ill veterinary to catheter care and monipatients has become increasingly toring of animals (e.g., usclear over the past two decades, ing an Elizabethan collar to and nutritional support is now prevent animals from chewcommonplace. Although total ing the line or catheter). parenteral nutrition is now Thrombophlebitis is not an indication for termination more widely accepted, safer, of therapy but does require and easier than it once was, its relocation of the catheter. use is still not feasible for many Metabolic complications practices. Advances in the are much less common formulation of parenteral with PPN formulated using nutrition solutions, intravenous the calculations in this articatheters, and administration cle than with TPN. The techniques as well as more most common problem is hyperglycemia, which, if seconservative calculation of vere, can be managed with nutritional requirements have exogenous insulin. Hyperfacilitated the use of peripheral ammonemia or hypertriglyparenteral nutrition (PPN). ceridemia are uncommon Simplified administration and but can occur and usually fewer complications make PPN require reformulation of the a convenient and practical solution with reduced promethod of nutritional support tein or reduced lipid levels, respectively. Refeeding synin carefully selected patients. drome (characterized by hypokalemia, hypophosphatemia, and hypomagnesemia) also can occur but is unlikely. Another possible problem is congestive heart CO
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failure resulting from volume overload, especially when intravenous fluids are given in addition to the PPN. Metabolic complications are not always the direct result of the PPN but may be caused by the underlying disease. Septic complications are the most serious potential problem of PPN but can be minimized by adhering to strict protocols for mixing and handling solutions and monitoring animals. If fever or other signs of potential sepsis occur and other causes (e.g., peritonitis, urinary tract infection, pneumonia) are ruled out, cultures of the blood and PPN catheter should be performed. The complication rate is quite low, however, if strict protocols for mixing and administering PPN are observed. In a study conducted in our hospital of dogs and cats with pancreatitis receiving three-in-one compounded PPN, the only complications noted were metabolic (e.g., hyperammonemia, hypercholesterolemia, and hypertriglyceridemia) in 1 of 12 patients.13 No cases of thrombophlebitis or sepsis occurred.13 In a recently completed study of dogs and cats receiving a commercial PPN solution, 2 of 30 patients developed transient mild hyperglycemia and 2 developed phlebitis; sepsis was not noted.22 Other important parameters to monitor include body weight and signs of malnutrition. PPN is intended for animals that are not already debilitated, do not have large protein losses, and are expected to eat within 4 to 5 days. If the situation changes (e.g., the animal has increased vomiting or diarrhea or significant drainage from wounds or the condition persists for more than few days) or the animal begins to exhibit weight loss or decreasing serum albumin concentrations, it is important to change to TPN or a combination of PPN and low-dose enteral nutrition.
SUMMARY Many of the problems associated with TPN can be overcome by using PPN, but PPN should not be viewed as a replacement for TPN. Although it does not provide all nutritional requirements, PPN can be beneficial in appropriately selected patients. In addition, PPN reduces the risk of complications compared with TPN. Like TPN, however, PPN does have potential to cause major problems and thus should be administered with care; protocols for mixing and administering solutions as well as monitoring patients should be devised and strictly followed. The ease of use of PPN has made the benefits of parenteral nutrition more widely available to veterinarians and their patients. REFERENCES 1. Thatcher CD: Nutritional needs of critically ill patients. Compend Contin Educ Pract Vet 18(12):1303–1313, 1996.
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2. Rhoads JE, Dudrick ST: History of intravenous nutrition, in Rombeau JL, Caldwell MD (eds): Clinical Nutrition: Parenteral Nutrition, ed 2. Philadelphia, WB Saunders Co, 1993, pp 1–10. 3. Dudrick ST, Wilmore DW, Vars HM, Rhoads JL: Longterm total parenteral nutrition with growth, development, and positive nitrogen balance. Surgery 64:134–142, 1968. 4. Carter JM, Freedman A: Total intravenous feeding in the dog. JAVMA 171:71–76, 1977. 5. Nordenstrom J: Peripheral parenteral nutrition: Changing trends in intravenous feeding. Nutrition 8:440–441, 1992. 6. Barton RG: Immune-enhancing enteral formulas: Are they beneficial in critically ill patients? Nutr Clin Pract 12:51–62, 1987. 7. Mainous MR, Block EFJ, Deitch EA: Nutritional support of the gut: How and why. New Horizons 2:193–201, 1994. 8. Davenport DJ: Enteral and parenteral nutritional support, in Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders Co, 1995, pp 244–252. 9. Lippert AC, Armstrong PJ: Parenteral nutritional support, in Kirk RW (ed): Current Veterinary Therapy X: Small Animal Practice. Philadelphia, WB Saunders Co, 1989, pp 25–30. 10. Remillard RL, Thatcher CD: Parenteral nutritional support in small animal patients. Vet Clin North Am Small Anim Pract 19:1287–1306, 1989. 11. Dickerson RN, Brown RO, White KG: Parenteral nutrition solutions, in Rombeau JL, Caldwell MD (eds): Clinical Nutrition: Parenteral Nutrition, ed 2. Philadelphia, WB Saunders Co, 1993, pp 310–333. 12. Stokes MA, Hill GL: Peripheral parenteral nutrition: A preliminary report on its efficacy and safety. J Parenter Enteral Nutr 17:145–147, 1993. 13. Freeman LM, Labato MA, Rush JE, Murtaugh RJ: A retrospective evaluation of peripheral parenteral nutrition (PPN) in small animal patients with pancreatitis. Proc Int Vet Emer Crit Care Soc Meet:881, 1996. 14. Payne-James JJ, Khawaja HT: First choice for total parenteral nutrition: The peripheral route. J Parenter Enteral Nutr
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17:468–478, 1993. 15. Kane KF, Cologiovanni L, McKiernan J, et al: High osmolality feedings do not increase the incidence of thrombophlebitis during peripheral IV nutrition. J Parenter Enteral Nutr 20:194–197, 1996. 16. Bodoky A: Parenteral nutrition by peripheral vein, portal vein, or central venous catheter? World J Surg 10:47–52, 1986. 17. Lev-Ran A, Johnson M, Hwang DL, et al: Double-blind study of glycerol vs glucose in parenteral nutrition of postsurgical insulin-treated diabetic patients. J Parenter Enteral Nutr 11:271–274, 1987. 18. Fairfull-Smith R, Stoski D, Freeman JB: Use of glycerol in peripheral parenteral nutrition. Surgery 92:728–732, 1982. 19. Kehoe JE, Mihranian MH, Masser EL, et al: Use of 20% fat emulsion in peripheral parenteral nutrition. J Parenter Enteral Nutr 8:647–651, 1984. 20. Carpentier YA, Van Gossum A, Dubois DY, Deckelbaum RJ: Lipid metabolism in parenteral nutrition, in Rombeau JL, Caldwell MD (eds): Clinical Nutrition: Parenteral Nutrition, ed 2. Philadelphia, WB Saunders Co, 1993, pp 35–74. 21. Dibartola SP, Autran de Morais HS: Disorders of potassium: Hypokalemia and hyperkalemia, in DiBartola SP (ed): Fluid Therapy in Small Animal Practice. Philadelphia, WB Saunders Co, 1992, pp 89–115. 22. Freeman LM, Rush JE, Rozanski EA, et al: Nutritional support using a commercial glycerin/amino acid solution. Proc Int Vet Emer Crit Care Soc Meet:827, 1998.
About the Authors Drs. Zsombor-Murray and Freeman are affiliated with the Department of Clinical Sciences, School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts. Dr. Freeman is a Diplomate of the American College of Veterinary Nutrition.
