Elsevier

Nutrition

Volume 22, Issue 9, September 2006, Pages 952-955
Nutrition

International ward round
Vitamins and trace elements: Practical aspects of supplementation

https://doi.org/10.1016/j.nut.2006.06.004Get rights and content

Abstract

The role of micronutrients in parenteral nutrition include the following: (1) Whenever artificial nutrition is indicated, micronutrients, i.e., vitamins and trace elements, should be given from the first day of artificial nutritional support. (2) Testing blood levels of vitamins and trace elements in acutely ill patients is of very limited value. By using sensible clinical judgment, it is possible to manage patients with only a small amount of laboratory testing. (3) Patients with major burns or major trauma and those with acute renal failure who are on continuous renal replacement therapy or dialysis quickly develop acute deficits in some micronutrients, and immediate supplementation is essential. (4) Other groups at risk are cancer patients, but also pregnant women with hyperemesis and people with anorexia nervosa or other malnutrition or malabsorption states. (5) Clinicians need to treat severe deficits before they become clinical deficiencies. If a patient develops a micronutrient deficiency state while in care, then there has been a severe failure of care. (6) In the early acute phase of recovery from critical illness, where artificial nutrition is generally not indicated, there may still be a need to deliver micronutrients to specific categories of very sick patients. (7) Ideally, trace element preparations should provide a low-manganese product for all and a manganese-free product for certain patients with liver disease. (8) High losses through excretion should be minimized by infusing micronutrients slowly, over as long a period as possible. To avoid interactions, it would be ideal to infuse trace elements and vitamins separately: the trace elements over an initial 12-h period and the vitamins over the next 12-h period. (9) Multivitamin and trace element preparations suitable for most patients requiring parenteral nutrition are widely available, but individual patients may require additional supplements or smaller amounts of certain micronutrients, depending on their clinical condition.

Introduction

Trace element and vitamin requirements are increased during critical illness and in chronically depleted patients, and their supplementation may influence the outcome of the disease. Further, whenever parenteral nutrition becomes necessary, micronutrients are an essential part of it. During the 2005 meeting of the European Society for Parenteral and Enteral Nutrition, which took place in Brussels, Belgium, two well-known specialists in the field, Mette M. Berger from the University of Lausanne (Lausanne, Switzerland) and Alan Shenkin from the University of Liverpool (Liverpool, United Kingdom), came together to discuss the role of micronutrients in parenteral nutrition and to answer practical clinical questions from the audience.

A. Shenkin: The correct strategy is to give micronutrients always from the very beginning of artificial nutritional support, and to give it daily—because if you do not, first, patients will fall behind, and second, many patients are already starting out depleted, because by the time they start nutritional support they will have had a history of disease. There may have been weeks of developing disease or complications and, therefore, to start artificial nutrition without giving micronutrients seems completely illogical. I know one can argue that there is no evidence of benefit when directly comparing people who get complete nutrition for the first few days against those getting inadequate nutrition. But I would say there are times when you do not need evidence for common sense. And common sense says, why put patients at risk?

M. Berger: As a clinician who is treating the critically ill, I totally agree with this. There is evidence that it is deleterious not to give micronutrients from the very beginning. One most obvious case for that is the infusion of high doses of glucose and the development of an acute thiamine deficiency.

A. Shenkin: It is not just in the critically ill. Any patient who has been depleted, with a poor intake for more than just a few days, is at risk from what is called the refeeding syndrome. This includes not only acute hypokalemia and hypophosphatemia, as a result of rapidly increased uptake into cells, but also the fact that vitamins, especially thiamine, and trace elements such as zinc are required in higher amounts. As soon as the patient’s metabolism becomes anabolic, receiving energy and substrates, the requirement for micronutrients rises. Therefore, critically ill and chronically depleted patients need micronutrients as part of their artificial nutritional support from the very beginning.

M. Berger: This is particularly true in parenteral nutrition, but may also be true in enteral nutrition. For specific patients, whether chronic or acute, even the enteral feeds might be too low in micronutrients.

A. Shenkin: What was said before also holds true for lipid-soluble vitamins that are stored in the body, because it is not sensible to put a patient at risk by depleting his reserves. Of course, a patient can survive longer on his fat-soluble vitamin reserves than on his water-soluble vitamin or trace element reserves. However, because all of the micronutrient supplements are mixtures—for good reasons—if you’re going to give them, you give a complete mixture.

M. Berger: You should leave the patient his reserves—they are built up for a purpose.

A. Shenkin: This is a difficult topic, and it depends on the individual patient. First, an assessment of the micronutrient status is not done on the basis of laboratory measurements. The intake, the losses, and the requirements of the patient play a role. The effects of the disease and the length of the disease on the requirements need to be taken into account. Blood tests might be of some help in some groups of patients, but their value is limited. By using sensible clinical judgement, it is possible to manage patients with only a small amount of laboratory testing.

M. Berger: When I measure blood levels, I do it for other reasons—to justify continued supplementation for reimbursement purposes or for research and teaching purposes. In patients with major burns in the intensive care unit, we determine selenium, zinc, C-reactive protein, prealbumin and albumin weekly because as a clinical protocol these patients receive 3 wk of trace element supplements. Then we stop, but we do restart supplementation if the laboratory data show levels below those we know from our research are associated with deficiency. However, we do not analyze vitamins or other trace elements on a regular basis.

A. Shenkin: With sufficient experience and understanding of the changes that are taking place, it is often possible to make an informed interpretation, especially if you are looking at sequential changes in relation to changes in the inflammatory process. Therefore, a key measurement is C-reactive protein. For example, one single test result showing that zinc is low is of no value—the zinc might be low because the albumin is low, or because the zinc:albumin ratio is low, which is a typical result of inflammation, and once the C-reactive protein falls, the albumin goes up and the zinc comes up too. On the other hand, if there is any suggestion of an acute selenium, zinc, or thiamine deficiency, for example, immediate supplementation is indicated. Blood samples may be taken, but you cannot wait for the results.

M. Berger: We do a systematic assessment of the condition of our patients on admission in the intensive care unit. Basically, if there is no history of underfeeding or of acute suppression of intake (generally iatrogenic due to hospitalization), micronutrient deficiency is rare. However, in patients who are in the early period of recovery from critical illness, and who we now know are at risk, we will intervene, even though we might not have clear clinical evidence of a deficiency. Burns patients quickly develop acute deficits in some micronutrients, and to prevent this turning into an acute deficiency state immediate substitution is essential. The same is true for patients with acute renal failure who are on continuous renal replacement therapy or dialysis, because they have enormous losses in the ultrafiltrates, too. A third group of patients with negative balances, although not as severe, are the major trauma patients.

A. Shenkin: Nowadays, we would regard any patient who actually develops a micronutrient deficiency state while in our care as a severe failure of care. If somebody reaches an acute selenium or thiamine or zinc deficiency state, with all the signs and symptoms, then we have handled that patient badly. Clinicians need to treat severe deficits before they become clinical deficiencies.

M. Berger: Cancer patients generally have cachexia, for obvious multifactorial reasons. They have low intakes and are at risk of deficiency. Other groups at risk are pregnant women with hyperemesis and people with anorexia nervosa.

A. Shenkin: It depends very much on the phase of their illness and the treatment they are receiving. A number of cancer patients will have severe reactions to chemotherapy, radiotherapy, or surgery, which may put them into a much higher-risk group than others.

M. Berger: It is a simple fact that you cannot provide macrosubstrates without micronutrients—this is nutrition.

A. Shenkin: There are some products that are better than others, and there are some countries that still do not have access to micronutrient supplements.

M. Berger: Most of the products available in Europe are conceived for home total parenteral nutrition or for stable patients only, and most of these products are adequate. Regarding acutely ill patients, the situation is completely different.

A. Shenkin: The requirements for an absolutely stable population, on the one hand, and for a hospitalized, already deficient population, on the other, are totally different. This has been the challenge that manufacturers have had to face, and producing an optimal preparation for all groups at risk is almost impossible. The final formula will always be a compromise, because you cannot have one preparation for home feeders, another one for surgical patients, a third for cancer patients, a fourth for infected patients, a fifth for patients on dialysis, etc. The commonly used preparations are compromise preparations, and they contain a higher micronutrient concentration than is necessary for basic supply, but not so much more as to be harmful for a patient on home parenteral nutrition. However, a chronically depleted patient or a severely burned one who needs more zinc and more selenium will receive too much manganese and too much chromium and iron if the doctor simply doubles the dose of the whole mixture. The original American recommendations were to have a core supplement to which single ampoules of zinc, selenium, or other elements can be added for specific patients.

M. Berger: The French company Aguettant is providing such single supplements. Apart from this, there has been almost no change for the last two decades. Few new products are available, although we have learned a lot, and the information is there to develop better products. Dealing with the current question, our practice is to deliver the daily basic supply and then, for specific patients, to give certain supplements in addition.

A. Shenkin: If the gut is available for minimal enteral nutrition—and an increasing number of patients will get at least some of their nutrition from some form of enteral supply—a supplement to provide micronutrients enterally rather than parenterally would be of great advantage. The supplements currently available are very poor for enteral supply.

A. Shenkin: Manganese is an essential trace element and is absolutely essential for a variety of enzymes. Mitochondrial enzymes, for example, depend on it. Hypermanganesemia can occur in patients with cholestatic disease, because manganese is excreted in the bile. As the patient’s liver function becomes abnormal, manganese increases. Especially in long-term feeding, this can become a serious problem, and it is often the long-term–fed patients who develop some form of cholestatic disease. If the patient still needs artificial nutrition, treatment can be very difficult. Without manganese-free products, we need to reduce all the micronutrients, which is not a good solution. It would be perfect to have a preparation that is almost manganese free—a specific, tailored preparation for patients with liver disease—in the same way that you have a special amino acid preparation for patients with renal disease.

M. Berger: We really should have manganese-limited or -restricted solutions, probably for all patients, because manganese is a contaminant. I have never seen a condition of acute manganese deficiency; however, manganese intoxication has been described, which should be considered in modern products—a low-manganese product for all, and a manganese-free one for certain circumstances.

M. Berger: This is our hypothesis in the most sick patients. The theory is that giving micronutrients to these patients may reduce oxidative stress and balance defence mechanisms. There is a study with 205 patients that shows a trend toward an improved outcome in terms of acute or persistent renal failure and length of stay. With 205 patients, the study was not able to reach statistical significance. But all the studies are pointing in the same direction and a meta-analysis would probably reach significance. Therefore, some specific categories of very sick patients may benefit during the acute phase from micronutrient support only, but the majority of patients do not. With that majority of patients, we would start complete nutritional support, including micronutrients, after the acute phase is over. Another aspect that has come out of our daily practice is that we give thiamine to all patients who come into our intensive care unit, independent of feeding.

M. Berger: Our burn patients receive very large amounts of copper, selenium, and zinc for 3 wk. These trace elements are infused over 12 h. For research purposes, we collected 24-h urine and measured urinary excretion. Indeed, the patients receiving those trace elements increased their excretion proportionally, but did not excrete the amount that was delivered to them. In another study involving trauma patients, we infused the trace elements, and especially selenium, faster, and we had the largest losses. So clearly, if the water-soluble agents are infused too fast, you will find most of it in the urine. Providing normal amounts, which was what the control group received, resulted in some minor increase of the urinary excretion.

It is also worth noting that, as for all nutrition, micronutrients should ideally be provided enterally, because the gut normally acts as to regulate absorption in relation to need, which can be a valuable safety mechanism. However, in the critically ill, gut function is unreliable, the sicker the patient the more unpredictable is the absorption. Therefore, the choice of route of delivery depends on 1) the availability of the gut and the hemodynamic status and 2) the objective of supplements, if a basic nutritional purpose is the aim, then enteral supply may be adequate; however, if large doses are to be delivered for antioxidant purposes or to correct major deficits, only the intravenous route guarantees the bioavailability of the supplements.

A. Shenkin: Physiologically, micronutrients should be infused over as long a period as possible. However, the problem is the potential interactions in the bag. Trace elements are entirely stable, but some of the water-soluble vitamins are not. Especially ascorbic acid is extremely labile and interacts with copper, so the ascorbic acid just disappears. Because it only makes sense to give the water-soluble vitamins together with the fat-soluble vitamins with the whole mixture, the best compromise is to add the vitamins at the last moment into the bag. They should be added fresh, to minimize the time for potential interactions. What one could conceivably think of is a strategy of infusing the trace elements over a 12-h period and the vitamins over the next 12-h period, every day. It might be ideal to have a multicompartmental bag to keep them separate and so minimize interactions.

M. Berger: We have infused them in separate bags—in our antioxidant study and in the burns study, in the unit in general. We have chosen that policy because everything else did not make sense—because we measured losses or observed precipitation with the higher doses we were giving. Practically, you could use a “piggy-back” arrangement with an industrial solution where you just switch at the right time from one to the other, trace elements for the first 12 h, vitamins for the next 12 h.

A. Shenkin: You can do this form of sequential infusion in an intensive care unit, but it is much harder in a general ward.

M. Berger: Patients on home total parenteral nutrition and other stable patients are probably easier to manage, so maybe in these cases you could combine the micronutrients in the simple way, but we are lacking the studies.

A. Shenkin and M. Berger: We always cover the vitamin bags in our unit.

M. Berger: An important argument for a clinician is a company that cares, that cares about the patient, and that tries to improve the general basic care. It does not necessarily have to have a ground-breaking, new product but should provide a basic, high quality of care and show concern. I think that’s all.

A. Shenkin: The debate around vitamin supplements is not quite as acute—there is more need to update and differentiate the trace element preparations. Liver disease, for example, affects the trace element requirements much more than it affects the vitamin requirements.

M. Berger: There has been only one recent trace element product launched on the European market. It is better balanced than the older preparations, especially regarding selenium and zinc.

Section snippets

Conclusions

This discussion on some practical aspects of micronutrient supplementation represents the views of two European specialists in this field. Others may have a different point of view, and Nutrition would welcome correspondence on any of the points raised.

Acknowledgments

The authors are grateful to Baxter Healthcare in Germany for arranging this interview, to Gabriele Luft for presenting the questions, and to H. C. Thuro, Dr.Med., for preparing the transcript.

References (0)

Cited by (80)

  • Phytochemicals as bioactive ingredients for functional foods

    2023, Recent Frontiers of Phytochemicals: Applications in Food, Pharmacy, Cosmetics, and Biotechnology
  • Immunomodulatory Supplements

    2022, Encyclopedia of Infection and Immunity
  • Vitamins and SARS-CoV-2

    2022, Application of Natural Products in SARS-CoV-2
  • Nutraceutical-A deep and profound concept

    2021, Nutraceuticals and Health Care
  • Factors associated with not meeting the recommendations for micronutrient intake in critically ill children

    2016, Nutrition
    Citation Excerpt :

    However, the beneficial role of high amounts of antioxidant micronutrients on the prognosis is not yet clearly defined [36,37]. Therefore, vitamins and trace elements should be provided at the recommended doses from the first day of nutritional support, aiming to improve antioxidant function and prevent deficiencies [38–40]. In conclusion, malnutrition, age <1 y, heart disease, the use of alpha-adrenergic drugs, and renal replacement therapy are factors associated with not meeting the recommendations for at least one micronutrient in children receiving enteral nutrition during their stay in the ICU.

View all citing articles on Scopus
View full text