Parenteral nutrition is widely used in companion animal medicine, and standardized protocols for preparation of PN admixtures have maximized safety of administration. However, the addition of lipids to PN admixtures still raises concerns about coalescence of lipid particles; such coalescence may result in the formation of particles that are sufficiently large to block small pulmonary blood vessels. To reduce the risk of embolism associated with such coalescence, the FDA presently recommends administration of a single lipidcontaining PN admixture preparation at room temperature for no longer than 24 hours.1 An informal survey of US and Canadian veterinary teaching hospitals conducted by one of the authors (EJT) revealed that the FDA recommendation has been adopted by many institutions but that clinicians at other establishments administer PN solutions for 48 hours or longer.
A lipid-containing solution is considered unsuitable for use when > 0.4% of its lipid particles are larger than 5.0 μm in diameter.2–11 The typical diameter of chylomicrons in the bloodstream is 0.4 to 1.0 μm. An abundance of large particles in the admixture puts an animal that is receiving PN at risk for development of lipid-induced pulmonary emboli, because the internal diameter of pulmonary capillaries is 4 to 9 μm.2,4,10-14
Lipid particles have a tendency to coalesce into larger particles. The initial stages of lipid particle degradation include what is termed as creaming, during which lipid particles rise to the surface of an emulsion, and flocculation, during which individual lipid particles become associated with each other in groupings. Both of these early stages of degradation can be reversed by agitation of solutions. However, once the particles coalesce into larger particles, degradation is irreversible.
Because agitation of a lipid-containing admixture reverses lipid particle creaming and flocculation, agitation should slow the progression of coalescence and thereby prolong the period in which administration of such an admixture is considered safe. Similarly, use of an appropriately selected filter during delivery of the PN admixtures should be able to successfully remove coalesced lipid particles of embolic size, which would also potentially extend the duration of use of an admixture preparation. Results of previous research indicate that PN admixtures containing lipid emulsions can be kept for as long as 1 week at refrigeration temperatures (4°C) prior to their safe administration over a 24-hour period to humans, suggesting that keeping a PN admixture at refrigeration temperatures during administration should likewise prolong the preparation's period of safe administration.7,15-19
In published retrospective studies20–22 of PN usage in dogs and cats, bags of PN solutions were either administered immediately or stored for as long as 5 days at refrigeration temperatures prior to administration. Although it was not always specifically stated in those reports, it appeared that a single bag of PN was not administered to a patient for more than 48 hours. Mechanical complications (eg, catheter occlusions or dislodgements and development of thrombophlebitis) developed in 21%21 to 46%20 of treated animals. Hyperglycemia was another common complication ranging from 20%22 to 75%20 of all patients, with cats seemingly more affected than dogs. Other metabolic derangements detected in animals receiving PN were hypoand hypernatremia, hypoand hyperkalemia, hypoand hypercalcemia, and hypoand hyperphosphatemia. However, the proportions of the 3 study populations that developed these metabolic derangements were much less than those that developed hyperglycemia: only as many as 10% of dogs and cats in 1 study,20 34% of cats in another study,21 and 11% of cats in a third study.22 There was an overall low rate of septic complications; in 2 studies,20,22 septic complications were not detected in cats or dogs, and PN-associated sepsis developed in 6% of cats in another study.21 Lipemia was evident in 46% of cats and dogs20 and 13% to 24% of cats.21,22 No embolic respiratory complications were noted in any veterinary studies.
The purpose of the study reported here was to determine whether veterinary PN admixtures that are kept at room temperature (23°C) can be used for more than 48 hours after preparation without development of excessive lipid particle coalescence and whether lipid particle coalescence is prevented by filtration, refrigeration, or agitation of the preparations. By use of TEM, the intent was to evaluate the change in lipid particle size distribution in bags of standard veterinary PN admixture over time at room temperature; the goal was to determine whether prolonged duration of bag hanging (> 24 hours) increased the embolic risk of PN administration because of the development of an unacceptable proportion of large lipid particles (ie, those > 5 μm in diameter). We were also interested to investigate whether the duration of safe administration of an admixture could be prolonged by physical manipulations of the PN admixture. If the duration of safe administration of each lipid-containing admixture can be extended (> 24 hours), the result would be cost savings for clients. At our institution, compounding fees and bagadministration set costs account for as much as 75% of the daily cost of PN administration. Prolonged use of admixture preparations would also be convenient for clinicians and pharmacists, especially over weekends and holidays when pharmacy services may be limited or unavailable. Our hypotheses for the present study were that a standard lipid-containing veterinary PN admixture can be kept in a static position at room temperature for more than 48 hours prior to the development of an unacceptable proportion of large lipid particles (with their inherent increased risk of embolism) and that agitation, refrigeration, and filtration of an admixture preparation will delay increases in size distribution of lipid particles that would be considered unsafe.
Transmission electron microscopy
Photon correlation spectroscopy
3-in-1 mixing container, Abbott Laboratories, North Chicago, Ill.
50% dextrose injection, Baxter Healthcare Corp, Deerfield, Ill.
Intralipid 20%, Baxter Healthcare Corp, Deerfield, Ill.
Aminosyn 8.5% sulfite-free crystalline amino acid solution (Na+, 78 mEq/L; Cl−, 86 mEq/L; K+, 66 mEq/L; Mg2+, 10 mEq/L; acetate, 61 mEq/L; and PO4−, 30 mEq/L), Abbott Laboratories, North Chicago, Ill.
Vitamin B injection solution, Phoenix Pharmaceutica Inc, St Joseph, Mo.
Abbott Plum A+ infusion IV pump system, Abbott Laboratories, Abbott Park, Ill (used in groups 2 through 5) and Heska Vet/IV 2.2, Heska Corp, Fort Collins, Colo (used in group 1).
Lab-Line lab rotator (31 × 31 cm), Barnstead International Products, Dubuque, Iowa.
Supor sterile syringe filter, Baxa Corp, Englewood, Colo.
Carbon support film on specimen grid on 200 mesh copper, Electron Microscopy Sciences, Hatfield, Pa.
TEM-JEOL 1200 EX, Japan Electron Optics Limited, Tokyo, Japan.
Adobe Photoshop, version CS2, Adobe Systems Inc, San Jose, Calif.
Fovea Pro, version 4.0, Reindeer Graphics, Asheville, NC.
Microsoft Excel, Microsoft Corp, Redmond, Wash.
SigmaStat, version 3.0, SPSS Inc, Chicago, Ill.
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