Editorial Review by Bruce R. Bistrian, MD, PhD
Division of Clinical Nutrition
Beth Israel Deaconess Medical Center
One Deaconess Road Boston, Massachusetts 02215

Introduction

The prevalence of malnutrition has been well documented in a wide variety of patient populations.^1-5 Surgical patients and the elderly appear to be at greatest risk.^2,6 Accordingly, vitamin supplementation is an important component of nutritional management for patients receiving parenteral nutrition support.

Vitamins are essential nutrients. They are needed to maintain cellular integrity through effects on structural protein and antioxidant protection of membrane lipids. Vitamins are also required to sustain cellular metabolism; in fact, they are necessary cofactors in such a wide range of metabolic processes that vitamin deficiencies can significantly impair cellular and organ function and recovery from illness.⁷ Studies in elderly people indicate that deficiencies in micronutrients can compromise cellular immune function and that supplementation with multivitamins can improve the immune response.⁸

Vitamins constitute an important component of nutritional support for patients receiving any form of parenteral nutrition support, including short-term, longterm, peripheral, and transitional parenteral nutrition. During metabolic stress, especially in the critically ill, vitamin needs may increase considerably. It is recommended to use a daily multivitamin infusion to meet these increased needs.^7,9

Increased Vitamin Needs in Many Disease States

Many disease states, particularly burn injury and those involving the gastrointestinal tract, are commonly associated with significant vitamin imbalances. Diminished intake is frequently the principal underlying etiology, although impaired absorption can also be an important cause of fat-soluble vitamin deficiency.^10,11

Inflammatory Bowel Disease

Numerous water-soluble and fat-soluble vitamin deficiencies can occur in inflammatory bowel disease. In Crohn's disease, malabsorption is the primary cause of fat-soluble vitamin deficiencies.¹¹ Subclinical vitamin A deficiency is prevalent in inflammatory bowel disease.¹² Patients with plasma retinal concentrations less than 0.8 µmol/L (22.9 µg%) run a high risk of night blindness and should receive supplementation.¹² Low circulating levels of 25-hydroxyvitamin D are found in up to 79% of patients with Crohn's disease,¹³ primarily as a result of malabsorption. Endogenous losses are also known to occur.¹⁴

Deficiencies of water-soluble vitamins, especially folate, vitamin B12, and vitamin C, can occur in patients with inflammatory bowel disease. Folate deficiency may lead to megaloblastic anemia. The severity of vitamin B12 malabsorption varies with the extent of the disease. The patient with terminal ileal disease and/or resection is particularly at risk for vitamin B12 deficiency.^11,15 Vitamin B12 malabsorption can also be due to bacterial overgrowth.¹⁴ Patients with Crohn's disease often have low vitamin C intake.¹¹ Serum and white blood cell vitamin C concentrations are significantly lower in patients with Crohn's disease than in normal control subjects.¹⁵ Patients with fistulous tracts may have especially low serum vitamin C levels.^11,16

Liver Disease

There is a high incidence of malnutrition in patients with liver disease.¹⁷ Micronutrient derangements have been noted in several categories of end-stage liver disease, including chronic active hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, and acute or subacute hepatitis.¹⁸ Thiamine deficiency is commonly associated with alcoholism. It can be brought on through a combination of impaired absorption and utilization of thiamine by the liver, increased requirements, and possibly an apoenzyme defect.¹⁹ Patients with a history of alcohol abuse who are undergoing total parenteral nutrition (TPN) are particularly susceptible to Wernicke's and Korsakoff's syndromes.^19,20

Renal Disease

In patients with renal failure, there is a high risk of malnutrition because of coexisting catabolic illness and reduced nutritional intake.²¹ Two recent studies concluded that critically ill patients treated by continuous renal replacement therapy had reduced concentrations of vitamin C, vitamin E, folic acid, and pyridoxal phosphate (metabolized and phosphorylated form of vitamin B6).^9,22

Short-Bowel Syndrome

Many patients who receive TPN have short-bowel syndrome. Nutrients that normally have an enteropancreatic or enterohepatic circulation may be lost in large amounts since endogenous intestinal secretions are not effectively reabsorbed. Vitamins with enteric cycles that can be disrupted in patients with short-bowel syndrome include fat-soluble vitamins, vitamin B12, and folate.²³

AIDS-Associated Wasting

Malnutrition is common in patients with acquired immunodeficiency syndrome (AIDS). It is caused by both the disease itself and the opportunistic infections that may result in diarrhea, malabsorption, and caloric deficiency.²⁷ Evidence of folate and vitamin B12 deficiency has been reported in human immunodeficiency virus (HIV)-infected individuals.^25-27 Patients with AIDS associated wasting who receive TPN should receive a daily multivitamin infusion to help meet increased vitamin needs.

Cancer

The potential for overall malnutrition, as well as for micronutrient deficiencies, is particularly high in certain cancer patients due to numerous factors causing impaired absorption and heightened needs. These include surgical interventions, chemotherapy, and radiation therapy. Serum levels of vitamin B1, vitamin B2, vitamin B6, and niacin have been shown to be decreased in up to 40% of cancer patients, indicating a need for adequate supplementation.²⁸ Multivitamin supplementation helps prevent symptoms of deficiency in cancer patients who develop progressive cachexia as a consequence of malnutrition.

Acute Respiratory Distress Syndrome (ARDS)

Oxidative damage by reactive oxygen species has been implicated in tissue injury occurring in ARDS.²⁹ In patients with this syndrome, the antioxidative system is severely compromised at the onset of disease and continues throughout the course of illness. Moreover, a progressive increase of lipid peroxidation end products in the plasma provides additional evidence of elevated oxidative stress. In fact, plasma levels of ascorbate, a-tocopherol, and ß-carotene are reduced in patients with ARDS, emphasizing the need for supplementing with these nutritive antioxidants.²⁹

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). These guidelines are an important foundation for meeting minimum needs.³⁰ They are based on the recommended dietary allowances (RDAs) of the National Academy of Sciences/National Research Council (NAS/NRC). Watersoluble vitamins are provided in excess of the RDA to meet the heightened needs of patients for whom TPN is necessary.³⁰ The critically ill or stressed patient frequently has an increased micronutrient demand to fuel the augmented enzymatic processes associated with hypermetabolism; therefore, it is important to supplement the TPN formula with a standard, multivitamin solution, once daily.

M.V.I.-12®, from aaiPharma®, a multivitamin formulation for infusion, matches the NAG-AMA guidelines for parenteral multivitamins. This formulation makes available a combination of important fat-soluble and water-soluble vitamins in an aqueous solution, specifically for incorporation into intravenous infusions. M.V.I.-12® is indicated as a daily multivitamin maintenance dosage for adults and children aged 11 years and older receiving parenteral nutrition. It is contraindicated in patients with a known hypersensitivity to any of the vitamins in this product or in patients with a preexisting hypervitaminosis.

One dose of M.V.I.-12® (10 mL final volume) should be administered 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 their clinical status. M.V.I.-12® does not contain vitamin K, which may have to be administered separately.

For complete M.V.I.-12® prescribing information, click here.

Summary

Patients receiving parenteral nutrition therapy have increased vitamin needs. Many disease states, including critical illness, inflammatory bowel disease, liver and renal disease, short-bowel syndrome, cancer, and AIDS-associated wasting, result in a higher demand for vitamins. 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 providing a reserve to protect against vitamin losses.

The clinician should not await the development of clinical signs of vitamin deficiency before initiating vitamin therapy. In most cases, the use of a multivitamin product obviates the need to speculate on the status of individual vitamin nutriture. Prescribing multivitamin supplementation in a timely fashion for all patients with a likelihood of increased vitamin requirements is a potentially cost-effective means of favorably influencing a variety of patient outcomes. While it is difficult to attribute desired improvements such as shortened recovery times, fewer complications, and decreased length of hospital stay to any one component of a complete nutritional regimen, appropriate multivitamin supplementation is a fundamental requirement for effective nutritional therapy.

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