Critical Issues in Home Multivitamin Infusion
Editorial review by: Carol J. Rollins, MS, RD, PharmD, BCNSP
Coordinator for Nutrition Support
Clinical Pharmacist for Home Infusion
Arizona Health Sciences Center
Tucson, Arizona
David F. Driscoll, PhD
Senior Researcher, Nutrition/Infection Laboratory
Beth Israel Deaconess Medical Center
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Introduction
Vitamins constitute an essential component of short-term and long-term parenteral nutrition support because they are necessary to maintain the body's normal metabolic functions.1 During stress and periods of extended nutrition support, vitamin requirements may be increased as a result of loss, greater utilization, or both.1 For patients on this nutrition therapy, vitamin requirements must be met to ensure optimal nutrition support and recovery from illness.1
Although deficiencies of all vitamins, both fat- and water-soluble, can occur without proper supplementation, parenteral nutrition therapy may itself accentuate the rate of water-soluble vitamin loss. A higher demand for water-soluble vitamins, especially thiamine, can occur as carbohydrate intake rises.2 This article reviews both the need for multivitamin supplementation in patients receiving home parenteral nutrition (HPN) and the safety issues surrounding the prevention of vitamin loss through a variety of physiochemical processes.
Physiochemical mechanisms of vitamin loss
During total parenteral nutrition (TPN) therapy, vitamin losses can occur through 1 of 4 principal chemical degradation pathways: photodegradation/oxidation, sorption into plastic matrices, hydrolysis, and co-precipitation from degradation products of various hydrolytic and oxidation reactions.3,4 Additionally, several physiochemical factors—fat emulsions, trace metals, temperature, light intensity, and pharmaceutical adjuvants—may influence the rate of vitamin degradation.5
Photodegradation/Oxidation reactions
Photodegradation is directly influenced by luminous intensity. In accordance with Planck's theory, wavelength is inversely proportional to photon energy or light intensity. In other words, as wavelength decreases, energy increases. Fluorescent lights, with wavelengths ranging from 320 to 380 nm,3 therefore, are more damaging to vitamins in TPN formulations than visible light (wavelengths from 380 to 780 nm). Likewise, intense sunlight, which contains high-energy ultraviolet rays, is more damaging to vitamins than artificial lighting.
Vitamin A is especially susceptible to photodegradation.5 The lighting conditions during HPN infusion may, thus greatly influence vitamin A delivery to the patient. Most patients infuse HPN at night when exposure to photodegradation is minimized. Patients electing daytime infusion of HPN are at greatest risk of vitamin A deficiency from photodegradation of the vitamin.
Adding the multivitamin preparation, M.V.I.®-12 (multi-vitamin infusion), immediately prior to HPN infusion eliminates the risk of vitamin loss during storage and warming to room temperature for infusion. Rapid photodegradation of the multivitamins with exposure to direct or indirect sunlight may still occur after the infusion begins. Use of a light-occlusive covering on bags of HPN is required to prevent loss of vitamin A due to photodegradation. Admixture of a lipid emulsion with the HPN formulation may also provide some protection from photodegradation by slowing the decomposition of vitamin A.5,6
Sorption losses
Sorption is the loss of drugs into semipermeable plastic parenteral containers. For example, vitamin A is associated with substantial sorption within the plastic matrix of TPN bags.4 The combined processes of photodegradation and sorption may account for substantial losses of vitamin A and can eventually lead to clinically significant deficiency in susceptible patients.6,7
Hydrolysis reactions
Hydrolytic degradation reactions often result in the splitting of one chemical constituent into 2 or more degradation products that retain little to none of the pharmacological or nutritional actions of the parent compound.3 In the case of vitamins, thiamine stability can be significantly challenged by the presence of the antioxidant sodium bisulfite, a common pharmaceutical adjuvant.8
Co-precipitation from degradation products
An unfavorable chemical reaction can occur when the degradation product of a parent compound participates in the formation of insoluble products. For example, ascorbic acid can undergo a series of decomposition reactions to form oxalic acid. Calcium is a common daily additive to TPN admixtures, and free calcium readily reacts with oxalic acid to form calcium oxalate, an insoluble product.9
Use of a calcium salt that dissociates slowly or to a limited extent, such as calcium gluconate, reduces the risk of reactions dependent on the presence of ionized calcium. The concentration of reacting species (e.g., calcium salt and oxalic acid) can also be controlled by setting limits on the amount of the parent compound (e.g., calcium salt and ascorbic acid) added to the HPN formulation.
Daily inclusion of vitamins and micronutrients in HPN, rather than bulk administrations 1 to 2 times per week, avoids large concentrations of parent compounds. Limiting the time the reacting species are exposed to one another reduces the risk of reaction. Degradation is a time-dependent process. The longer the parent compound is exposed to the condition(s) leading to degradation, the greater the accumulation of degradation product(s). Addition of vitamins just prior to HPN infusion limits the time vitamins are exposed to degrading factors in the HPN formulation.10
Increased vitamin needs in HPN
Numerous disease states, particularly those involving the gastrointestinal tract, are commonly associated with significant vitamin imbalances. A variety of causes, including malabsorption, inadequate intake, and increased metabolic needs, contribute to these imbalances. Losses sometimes continue in a chronic fashion resulting in gradual appearance of symptoms characteristic of certain vitamin deficiencies.1
In the early years of HPN, patients with short-bowel syndrome represented the major population.4,7,11 The growth of HPN in the United States, however, was associated with a major shift toward wider use of this therapy in short-term clinical situations, such as AIDS and cancer.4 Active cancer is now the most common diagnosis of patients receiving HPN, and accounted for >40% of all new patients treated with HPN reported to the North American Home Nutrition Support Registry.12 Short-term parenteral nutrition therapy in the home setting is largely the result of the wider influence of managed care and home care on overall health care.11,12
A short-term course of HPN does not obviate the need for vitamin supplementation, especially water-soluble vitamin supplementation, because deficiencies can develop quickly. In addition to thiamine deficiency in both short- and long-term TPN patients, deficiencies of vitamins A, D, and E have been reported.7,13,14 Daily administration of the recommended quantity of a parenteral multivitamin preparation reduces the risk of patients developing vitamin deficiencies during HPN therapy. Patients with preexisting vitamin deficiencies and/or excessive vitamin losses may require supplementation with additional vitamins. Individual vitamin preparations are normally used for supplementation when a specific vitamin deficiency is noted. Multiple doses of the recommended quantity of a multivitamin preparation may be used on a short-term basis for patients with evidence of multiple vitamin deficiencies.
Thiamine status in HPN
Thiamine is a critical component involved in aerobic metabolism at 2 steps of the Krebs cycle.1,15 A chronic deficiency of thiamine may manifest as a neurologic deficit with symptoms characteristic of peripheral neuritis known as "dry beriberi." In rare cases, cardiac dysfunction from high-output failure can also occur and is referred to as "wet beriberi."16 The occurrence of severe clinical thiamine deficiency in patients receiving TPN 15-18 demonstrates the need to insure that all parenteral nutrition contains thiamine in adequate quantities. Dependence on dextrose as the primary caloric source increases the risk of deficiency for many HPN patients, as thiamine requirements are linked to carbohydrate intake.19 Risk of thiamine deficiency is also increased by thiamine degradation in the presence of bisulfite-containing amino acid solutions or TPN additives.17
Daily addition of an injectable multivitamin supplement containing thiamine (such as, M.V.I.®-12), or a single entity injectable thiamine product, immediately prior to infusion of HPN is, thus, important to insure appropriate delivery of thiamine.
NAG-AMA guidelines
The current guidelines for adult intravenous multivitamin formulations were issued by the Nutrition Advisory Group of the Department of Foods and Nutrition of the American Medical Association (NAG-AMA). Although not specifically formulated for the HPN patient, these guidelines are an important foundation for meeting minimum needs. They are based on the 1974 revision of recommended dietary allowances (RDAs) of the National Academy of Sciences/National Research Council.
Water-soluble vitamins are provided in excess of the RDA to meet the heightened needs of patients for whom TPN is necessary.20 In addition, recommendations for intravenous multivitamin preparations have accounted for anticipated losses from chemical reactions and interactions during use. The critically ill or stressed patient may have an increased micronutrient demand to fuel the body's increased metabolic demands and consequent tissue depletion of nutrients; therefore, it is important to supplement the TPN formula with a standard multivitamin solution daily. Patients with multiple vitamin deficiencies or with markedly increased requirements may be given multiples of the daily dosage for 2 or more days as indicated by the clinical status. When multiples of the formulation are used for more than a few weeks, vitamins A and D should be monitored occasionally to be certain that an excess accumulation of these vitamins is not occurring.
Summary
Patients who are receiving short-term and long-term HPN therapy have increased vitamin needs. The requirements for water-soluble vitamins, especially thiamine, increase as carbohydrate intake increases.2 Home parenteral nutrition itself can augment vitamin losses through physiochemical processes such as photodegradation/oxidation, sorption, hydrolysis, and co-precipitation from degradation products.3,4
Daily supplementation with a multivitamin infusion, based on the NAG-AMA recommendations, can maintain blood vitamin levels within normal parameters by meeting vitamin needs and protecting against vitamin losses. By using aseptic techniques and adding the multivitamin solution to the HPN admixture just prior to infusion, the home infusion professional can administer multivitamins safely and effectively.
References
1. Zaloga GP, Bortenschlager L. Vitamins. In: Zaloga GP, ed. Nutrition in Critical Care. St Louis, Mo: Mosby-Book Inc; 1993:217-242.
2. McCormick DB. Thiamine. In: Shils ME, Young VR, eds. Modern Nutrition in Health and Disease. Philadelphia, Pa: Lea & Febiger, 1988:355-361.
3. Newton DW. Physiochemical determinants of incompatibility and instability in injectable drug solutions and admixtures. Am J Hosp Pharm. 1978;35:1213-1222.
4. Howard L, Alger S, Michalek A, Heaphey L, Aftahi S, Johnston KR. Home parenteral nutrition in adults. In: Rombeau JL, Caldwell MD, eds. Clinical Nutrition: Parenteral Nutrition. Philadelphia, Pa: WB Saunders Co; 1993:814-839.
5. Smith JL, Canham JE, Wells PA. Effect of phototherapy light, sodium bisulfite, and pH on vitamin stability in total parenteral nutrition admixtures. J Parenter Enteral Nutr. 1988;12:394-402.
6. Billion-Rey F, Guillaumont M, Frederich A, Aulagner G. Stability of fat-soluble vitamins A (retinol palmitate), E (tocopherol acetate), and K1 (phylloquinone) in total parenteral nutrition at home. J Parenter Enteral Nutr. 1993;17:56-60.
7. Howard L, Chu R, Feman S, Mintz H, Ovesen L, Wolf B. Vitamin A deficiency from long-term parenteral nutrition. Ann Intern Med. 1980;93:576-577.
8. Scheiner JM, Araujo MM, DeRitter E. Thiamine destruction by sodium bisulfite in infusion solutions. Am J Hosp Pharm. 1981;38:1911-1913.
9. Das Gupta V. , Allwood MC, Louie N. Stability of vitamins in total parenteral nutrient solutions. Am J Hosp Pharm. 1986;43:2132.
10. Shils ME, Baker H, Frank O. Blood vitamin levels of long-term adult home total parenteral nutrition patients: the efficacy of the AMA-FDA parenteral multivitamin formulation. J Parenter Enteral Nutr. 1985;9:179-188.
11. Howard L. Home parenteral and enteral nutrition in cancer patients. Cancer. 1993;72:3531-3541.
12. Howard L, Ament M, Fleming CR, Shike M, Steiger E. Current use and clinical outcome of home parenteral and enteral nutrition therapies in the United States. Gastroenterology. 1995;109:355-365.
13. Shike M, Shils ME, Heller A, et al. Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect. Am J Clin Nutr. 1986;44:89-98.
14. Howard L, Ovesen L, Satya-Murti S, Chu R. Reversible neurological symptoms caused by vitamin E deficiency in a patient with short bowel syndrome. Am J Clin Nutr. 1982;36:1243-1249.
15. Velez RJ, Myers B, Guber MS. Severe acute metabolic acidosis (acute beriberi): an unavoidable complication of total parenteral nutrition. J Parenter Enteral Nutr. 1985;9:216-219.
16. Zak J III, Burns D, Lingenfelser T, Steyn E, Marks IN. Dry beriberi: unusual complication of prolonged parenteral nutrition. J Parenter Enteral Nutr.1991;15:200-201.
17. Schiano TD, Klang MG, Quesada E, Scott F, Tao Y, Shike M. Thiamine status in patients receiving long-term home parenteral nutrition. Am J Gastroenterol. 1996;91:2555-2559.
18. Vortmeyer AO, Hagel C, Laas R. Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition. J Neurol Neurosurg Psychiatry. 1992;55:826-829.
19. Van Way CW III. Vitamins and trace minerals. In: Van Way CW III, ed. Handbook of Surgical Nutrition. Philadelphia, Pa: JB Lippincott Company; 1992:56-69.
20. American Medical Association Department of Foods and Nutrition. Multivitamin preparations for parenteral use: a statement by the Nutrition Advisory Group. J Parenter Enteral Nutr. 1979;3:258-262.
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