Physical characteristics of total parenteral nutrition bags significantly affect the stability of vitamins C and B1: a controlled prospective study

BACKGROUND: Vitamin degradation occurring during the storage of total parenteral nutrition (TPN) mixtures is significant and affects clinical outcome. This study aimed to assess the influence of the TPN bag material, the temperature, and the duration of storage on the stability of different vitamins. METHODS: Solutions of multivitamin and trace elements at recommended doses were injected into either an ethylvinyl acetate (EVA) bag or a multilayered (ML) bag filled with 2500 mL of an identical mixture of carbohydrates (1200 kcal), fat (950 kcal), and amino acids (380 kcal). The bags were then stored at 4 degrees C, 21 degrees C, or 40 degrees C. Concentrations of vitamins A, B1, C, and E were measured up to 72 hours after compounding, using high-pressure liquid chromatography. RESULTS: Ten percent to 30% of vitamin C degradation occurred within the first minutes after TPN compounding. Vitamin C was more stable in ML bags (half-life: 68.6 hours at 4 degrees C, 24.4 hours at 21 degrees C, and 6.8 hours at 40 degrees C) than in EVA bags (half-life: 7.2 hours at 4 degrees C, 3.2 hours at 21 degrees C, and 1.1 hour at 40 degrees C). Moreover, appearance of dehydroascorbic acid in the TPN mixture did not compensate for vitamin C losses. Vitamin B1 was stable at 21 degrees C, but a 43% loss occurred at 40 degrees C after 72-hour storage in EVA bags. The other vitamins were stable in the TPN mixture stored in both bags at any temperature and without daylight protection. CONCLUSIONS: Degradations of vitamins C and B, are significantly reduced in ML bags compared with EVA bags. To prevent vitamin C deficiencies, its initial dose should be adapted to its degradation rate, which depends on the TPN bag material, the ambient temperature, and the length of time between TPN compounding and the end of infusion to the patient.     

Factors influencing the stability of ranitidine in TPN mixtures

The stability of ranitidine in TPN mixtures has been widely studied with varying results. The evidence suggests that ranitidine is unstable and should be added within 24 h of administration, although other reports indicate ranitidine is stable for at least 14 days. The causes of ranitidine degradation in TPN mixtures were therefore studied in mixtures without fat emulsion using a stability-indicating HPLC method. The results indicated that the stability of ranitidine at 5 degrees C depended on the commercial source of amino acid, additives and type of bag used. The principle mechanism of degradation was identified as oxidation. Ranitidine was more stable in EVA bags in the absence of the trace element additive, which appeared to accelerate ranitidine oxidation. Ranitidine was most stable in mixtures compounded in multi-layered bags. The results suggest TPN mixtures with ranitidine in multi-layered bags could be assigned shelf lives of at least 14 days at 5 degrees C, depending on the amino acid infusion used in the regimen.     

The stability of ascorbic acid in TPN mixtures stored in a multilayered bag

Because of the susceptibility of some vitamins to oxidation, they are not normally added to TPN mixtures until shortly before addministration. Vitamin C (ascorbic acid) is oxidised rapidly, especially in the presence of trace elements. The aim of this study was to investigate the stability of ascorbic acid in complete TPN mixtures in Ultrastab multilayer bags, which are designed to reduce oxygen transmission and thus oxidation, in comparison with standard EVA bags. Ascorbic acid content was determined in two typical TPN mixtures providing 16 g nitrogen, 2000 kilocalories, electrolytes, trace elements and multivitamins, with and without fat emulsion, during storage at 5 degrees C for up to 3 months. In EVA bags ascorbic acid degraded by more than 75% during 24 h and was undetectable in 2-3 days. In contrast, there was a comparatively small initial loss of 15-30% ascorbic acid in mixtures stored in multilayer bags, with little further loss during 1-3 months. Bags containing fat emulsion retained higher concentrations of ascorbic acid after storage compared to those without fat emulsion, but all mixtures in multilayer bags maintained 60-80% ascorbic acid activity after 3 months. Since ascorbic acid is the most oxygen-sensitive vitamin, complete TPN mixtures with vitamins could be compounded in multilayer bags for an extended shelf life, rather than admixing just prior to administration.     

Clinical adsorption and photodegradation of the fatsoluble vitamins A and E

The adsorption of the fat-soluble vitamins A and E to administration sets and their photodegradation was studied under varying conditions. Infusion bottles with or without photoprotectors (red plastic bags) were studied, as were systems exposed to the blue light, used in the treatment of hyperbilirubinaemia, which has a maximum emission spectrum at 450 nm. An IV bag containing lipids, carbohydrates, amino-acids, minerals and vitamins was also studied. Vitamin levels in all administration sets decreased by approximately 30% during the first 3h, except for those in the IV bag. Vitamins were best preserved in the IV bag, where 85-90% of both vitamins remained after 20h. Vitamin E appeared to suffer from both adsorption and photodegradation but to a lesser extent than vitamin A. Vitamin A displayed a greater tendency for adsorption. In order to avoid loss of vitamins during parenteral administration, we recommend that they should be administered as a bolus or during a limited period of 1 h, and that the system be protected from light.     

The influence of light on vitamin A degradation during administration

Vitamins are an essential part of total parenteral nutrition. Vitamin A is known to be very sensitive to light and may be absorbed to plastic containers and administration sets. The rate of loss of Vitamin A was therefore assessed from T.P.N. regimens in 3 litre bags during administration. Results indicated that Vitamin A palmitate was not absorbed to P.V.C. and degradation occurred during exposure to daylight, both in the bag and the administration set. Only 7 per cent of the added Vitamin A was delivered from a bag situated close to a source of daylight. Covering the bag reduced losses, although Vitamin A degradation in the administered set remained considerable. Moving the bag and set away from the source of daylight reduced degradation. Artificial light had no detectable effect on Vitamin A stability. Light-induced degradation can cause clinically significant losses of Vitamin A from T.P.N. infusions.     

Effect of Intralipid, amino acids, container, temperature, and duration of storage on vitamin stability in total parenteral nutrition admixtures

This study was designed to determine the stability of certain vitamins added to total parenteral nutrition (TPN) admixtures with or without Intralipid iv fat emulsion and with each of four amino acid solutions stored in either glass bottles or plastic bags at either ambient room (25 degrees C) or refrigerator (5 degrees C) temperature for a 48-hr period. Riboflavin and folacin were not affected by the experimental conditions. The presence of Intralipid resulted in higher levels of vitamin E due to Intralipid's inherent vitamin E content; no other experimental conditions affected vitamin E. Thiamin levels decreased in admixtures containing the amino acid solution C and stored at 25 degrees C. Vitamin A levels were lower in admixtures stored in plastic but were maintained in admixtures containing Intralipid and stored in glass bottles at either temperature. Vitamin C levels were maintained in admixtures stored at 5 degrees C for all experimental conditions. The greatest vitamin C losses occurred in admixtures containing amino acid solutions C or D stored in plastic bags, or containing D stored in glass bottles at 25 degrees C.     

Maintenance of vitamin and trace element status in intravenous nutrition using a complete nutritive mixture

Complete nutritive mixtures (CNM) of all intravenous nutrients including fat emulsions are being used increasingly because of their convenience. However, this may lead to chemical interactions and reduce the amount of active vitamins and trace elements made available to the patient. We have studied the effects on micronutrient status of provision of all nutrients in one 3-liter bag (CNM: amino acids, dextrose, Intralipid 20%, a nine-element trace metal mixture, and complete fat- and water-soluble vitamin mixtures) in 10 postoperative surgical patients [median intravenous nutrition (IVN) 14.5 days, range 7-38]. A similar group received the fat emulsion plus water- and fat-soluble vitamins as a separate infusion (SI) from a 3-liter bag (median IVN 14.0 days, range 8-28). Serum and urine magnesium, zinc, copper, manganese, chromium, and selenium, serum vitamins A, E, C, folate, and B12, RBC B1, B2 B6, and folate and leukocyte vitamin C were measured at weekly intervals. All patients in both groups maintained or improved their status for all the micronutrients analyzed. No significant differences between the CNM and SI groups were found in blood concentrations of any of the elements or vitamins. Only for urine copper did the CNM lead to increased excretion (1.51 +/- 0.59 mumol/24 hr; copper input 20 mumol/day), compared to SI (1.00 +/- 0.70 mumol/day, p less than 0.001 Mann-Whitney test) suggesting possible interaction. It is concluded that micronutrient status was maintained during short-term IVN with the CNM and that it did not lead to a significantly greater loss of vitamins or essential trace elements than the SI system.     

Vitamin Serum Level Variations Between Cycles of Intermittent Parenteral Nutrition in Adult Patients With Short Bowel Syndrome

Background: An alternative form of nutrition therapy for patients with short bowel syndrome (SBS) who do not have home parenteral nutrition (PN) available is the administration of the PN cycle during regular hospital admissions and oral vitamin supplement at home. The aim of this study was to evaluate serum levels of folic acid and vitamins A, B₁₂, C, and E before and after the PN cycle in patients with SBS. Materials and Methods: This research was conducted with 10 patients with SBS (less than 15 minutes of total barium transit time) who were receiving the PN cycle and oral vitamin supplement at home. Patients were evaluated regarding total food ingestion and oral vitamin supplement intake. Serum levels of vitamins were evaluated immediately after the end of each PN cycle (phase 1) and before the beginning of the next PN cycle (phase 2). Results: Patients’ nutrient ingestion was in accordance with recommendations for healthy individuals. Regarding the oral vitamin supplement intake, 20% of the patients presented low adherence. Although all patients had a normal serum level of folic acid and vitamin B₁₂, PN vitamin infusion during hospitalization and home oral vitamin supplement were not enough to make the serum levels of vitamins A, C, and E achieve normal values. Conclusion: This study documented that patients did not receive an adequate administration of oral vitamin supplements of vitamins A, C, and E through PN. More studies need to be conducted investigating higher doses of vitamin administration (oral or intravenous administration), assessing differences between water and liposoluble supplements.     

Micronutrient supplementation in parenteral nutrition in Spanish hospitals

Several years ago, it was recommended not to add vitamins or oligoelements to parenteral nutrition (PN) solutions and to administer them immediately after the addition of the micronutrients to avoid their decay. Nowadays, it has been observed that with multilayer bags, ternary mixtures and sunlight protection vitamins degradation is minimal. Daily intake of micronutrients is necessary in the critically ill, malnourished or long-term PN patients. Aiming at knowing the schedules of use of micronutrients in PN in Spanish hospitals and the way PN bags are prepared regarding the factors conditioning their stability, we undertook a telephone survey to the pharmacists in charge of PN at the different hospitals. We compared the data obtained with those from other surveys performed in 2001 and 2003. Pharmacists from 97 hospitals answered the questionnaire (answer rate 88%). The hospital sizes ranged 104-1728 beds. As compared to the data form preceding years, we observed a better adequacy to the current recommendations, although there are still 30% of the hospitals that administer micronutrients on an every other day basis independent of the clinical situation of the patients. In most of the hospitals, multilayer bags are used and/or sunlight protection and ternary mixtures. According to these results showing the different criteria for administering vitamins and oligoelements in PN solutions, it seems necessary to elaborate consensus documents that adapt to the reality of the diverse practices besides promoting the performance of well-designed clinical studies establishing the requirements under special clinical situations.     

Home parenteral nutrition in children: bioavailability of vitamins in binary mixtures stored for 8 days

Vitamin supply in children on long-term parenteral nutrition depends on the specific age-related needs and on the bioavailability of vitamins when introduced into nutritional bags. The present study aimed to investigate the vitamin status in children on home TPN receiving nutritional bags which had been stored during a prolonged period of 8 instead of 4 days and where the new vitamin preparation Cernevit has been introduced. 19 children aged from 5 months to 11 years receiving home parenteral nutrition, for 42 months on average, were studied. Daily vitamin supply for children above 2 years of age was: A 1050 ug, D 5.5 ug, E 10.2 mg plus 0.6 mg/g lipid (Intralipid), C 125 mg, B1 3.5 mg, B2 4.1 mg, B6 4.5 mg, biotine 69 mug; children who were younger than 2 years received half of these intakes. Water soluble vitamin status was only measured in children over 3 years old. Plasma levels remained stable and adequate for age, for most of the studied vitamins. Vitamin A concentration was inferior to 200 mug/l in 1 patient with hepatopathy. Plasma concentrations of vitamin E, which were initially below 6 mg/l in 4 patients, returned to normal during the study. Plasma levels of vitamin C were below 6.2 mg/l in several infants either temporarily (5 patients) or during the whole study period (2 patients). These results support a prolongation of the intervals between preparing batches of nutritional bags and also between deliveries. This results in a considerable reduction of costs, provided that plasma vitamin levels, specially vitamin C, are regularly monitored.     

Case report of an allergic reaction to parenteral nutrition in a pediatric patient

We report a 34-month-old girl with stage IV neuroblastoma who developed hives when parenteral nutrition (PN) containing amino acids, dextrose, electrolytes, minerals, vitamins, and trace elements was infused. Administration of diphenhydramine resulted in disappearance of the rash. Infusion of the PN solution without intravenous fat emulsion produced a similar rash with itching. The pediatric multiple vitamin (PMV) preparation was removed from the PN formula and the formula was infused without incident. The patient was maintained on PN and an oral vitamin supplement with no further complaints. Inadvertent administration of a PN solution containing PMV resulted in a recurrence of hives. Absence of any adverse reactions when the PMV preparation was removed from the PN solution and an allergic reaction when the multivitamin was added to the PN solution support the possibility that the allergic reaction was related to the infusion of the multiple vitamin preparation.     

Tissue levels of vitamin E (alpha-tocopherol) in response to continuous intravenous multivitamin infusion

Weanling rats were made vitamin E deficient over a 10-week course. Vitamin E was then provided at 4 IU/kg/day as a continuous infusion of the alpha-tocopherol in Berocca PN. Tissue samples of heart, lung, liver, and perinephric fat and plasma were analyzed for vitamin E levels at 24 and 72 hr. Compared to experimental controls that received a rat chow containing 372 IU/g mixed tocopherol, normal levels were achieved in the test group within 24 hr in plasma and liver. Lung and heart muscle levels were within the normal range by 24-72 hr, although significantly below the control level; fat levels did not normalize. Continuous infusion of vitamin E as tocopherol in a multivitamin preparation results in normal tissue levels in lung and liver in a fashion similar to that achieved by previously described methods of single bolus intravenous infusion or repeated subcutaneous injection.     

Effect of phototherapy light, sodium bisulfite, and pH on vitamin stability in total parenteral nutrition admixtures

The three sections of this study extend previous research into losses of vitamins A, C, E, thiamin, riboflavin, and folic acid from total parenteral nutrition (TPN) admixtures. First, phototherapy light on TPN admixtures containing one of four amino acid solutions was studied. Experimental conditions included presence or absence of Intralipid iv fat emulsion, plastic bag or glass bottle storage container, and storage time of up to 48 hrs. The second phase studied stability of the same vitamins (except vitamin E) for 48 hrs in admixtures containing the amino acid solution which has no bisulfite, in glass bottles; with or without Intralipid; and with added sodium bisulfite (final concentrations of 0, 1, 2, 3, 4, 5 and 10 mEq/liter). Third, vitamin C and thiamin levels were measured in admixtures containing the amino acid solution with no bisulfite, without Intralipid, stored in glass bottles with various bisulfite concentrations (0, 1, 2, or 3 mEq/liter) and three pH levels (5.5, 6.5, and 6.75 pH). Exposure of TPN admixtures to phototherapy light caused losses of vitamins A, C, and riboflavin. Intralipid inclusion significantly reduced losses of vitamin A and riboflavin, but did not appear to affect vitamin C levels. The smallest vitamin C losses were noted in admixtures containing amino acid solutions A or B. Phototherapy light did not affect thiamin levels. Bisulfite had no affect on vitamin C, riboflavin, or folic acid levels. Vitamin A levels were maintained with bisulfite concentrations less than 3 mEq/liter. At 3 mEq/liter bisulfite, admixtures with Intralipid showed 50% loss of vitamin A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parenteral vitamin requirements during intravenous feeding.

Serum vitamin levels of 40 patients undergoing parenteral nutrition over a 5-to 42-day period were studied while the subjects received daily water-soluble and once weekly fat soluble vitamin formulations intravenously. Initial serum deficiencies of vitamins A, C, and folate were noted in a large portion of the severely malnourished population. At the replacement levels used in this study a small number of patients developed subnormal levels of vitamins A and D. Improvement in levels for vitamin C and folate were noted for most patients. Vitamin B12 deficiencies were not noted in any patient. Currently available commercial vitamin preparations can be used with safety in the parenterally nourished population and recommended guidelines for weekly infusion of both water and fat soluble vitamins are presented.     

Effect of enteral feeding bag composition and freezing and thawing upon vitamin stability in an enteral feeding solution

The effect of enteral feeding bag composition and freezing and thawing upon the stability of riboflavin and vitamins A and E in an enteral feeding solution was tested. Feeding bags composed of either polyvinyl chloride or polyethylene were filled with an enteral feeding solution. The samples were frozen for 3 months, thawed in warm water, and allowed to stand in room temperature for 12 hr. Samples for vitamin analysis were obtained prior to freezing, upon thawing, and at 12 hr after thawing. No significant differences in vitamin stability due to bag composition or time were seen. These results support the viability of the concept of mixing large batches of enteral feeding solution, and freezing aliquots in individual feeding bags for later use.     

Effect of end-user preparation methods on vitamin content of fortified humanitarian food-aid commodities

The effect of cooking on vitamin stability in common fortified food-aid commodities was evaluated: corn–soy blend (CSB), cornmeal (CM), soy-fortified bulgur (SFB), and vegetable oil (VO). Thin CSB porridge, thick CM and SFB porridges, and dumplings fried in VO were prepared using average preparation parameters determined from the data collected in the field. Vitamin levels in pre- and post-cook samples were tested. In CSB thin porridge, vitamins C and E showed cooking losses of 53% and 18%, respectively; thiamin, folic acid, riboflavin, pantothenic acid, pyridoxine HCl, vitamin A, and vitamin B12 showed no significant losses. In CM thick porridge, thiamin, folic acid, riboflavin, and vitamin A showed no significant changes during cooking. In SFB, vitamin A was reduced by 33%, while thiamin, folic acid, and riboflavin showed no significant changes during cooking. In VO that was used to prepare dumplings, vitamin A losses of 6% occurred after one frying cycle. Vitamin A content of the dumplings, however, increased significantly during frying. With the exception of vitamins C and E in CSB and vitamin A in SFB and VO, typical cooking had little effect on vitamin stability.     

Fat-soluble vitamins in human lactation

Lactation has three distinct phases: colostrum, transition, and mature, with the quantity of fat-soluble vitamins and carotenoids tending to decline while the total fat content increases. The number of deliveries seems to be directly related to higher concentrations of beta-carotene and vitamin E in colostrum. Little is known about vitamin quantities during the other phases. In the present study, vitamin A and E concentrations during different phases of lactation were measured in primiparous and multiparous mothers to analyze the variation and suitability for the diet of a breastfed child. Phase of lactation and number of deliveries were highly significant for log mean vitamin A while only one phase showed significance for log mean vitamin E. There was a sharp decline in the levels of vitamin A and E in the course of the initial phase of lactation. The variability between measurements declined as colostrum transitioned to mature milk. There were significant measurable inter-group differences in retinol levels in milk obtained during early lactation. Vitamin A and E content can reach 2.5 and 1.4 times of levels recommended intake, respectively.     

Precipitation of trace elements in parenteral nutrition mixtures

Trace elements are an essential additive to parenteral nutrition (PN) mixtures. Previous studies have indicated that certain trace elements, in particular copper and iron, may interact with complete PN mixtures leading to precipitate formation. The causes of these incompatibilities have not been fully elucidated. The purpose of this study was to determine factors responsible for common trace element incompatibilities, using X-ray energy dispersive spectroscopy to examine the elemental content of precipitates isolated from stored PN mixtures with added trace elements. Results indicated that copper sulphide precipitated most rapidly in PN mixtures containing Vamin 9 and in mixtures stored in multilayered bags. Copper sulphide precipitation was delayed in PN mixtures containing Vamin 14 and was not observed in PN mixtures stored in EVA bags. Iron phosphate precipitates were observed in Synthamin-containing PN mixtures after storage, but this was prevented in mixtures containing vitamins stored in multilayered bags.     

Effects of vitamins E and A on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lipid peroxidation and other biochemical changes in the rat

The effects of vitamins A and E on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lipid peroxidation in the rat were investigated. Vitamin E markedly inhibited microsomal lipid peroxidation (malondialdehyde formation), but had no effect on glutathione peroxidase activity or glutathione (GSH) content, and did not protect against decreased body and liver weights. Furthermore, vitamin E had little effect on TCDD-induced lethality in rats. Vitamin A inhibited lipid peroxidation, elevated the activity of glutathine peroxidase and prevented a TCDD-induced decrease in GSH content in the liver. However, vitamin A did not inhibit the decrease in liver and body weights and provided little protection against TCDD-induced lethality. The activities of aryl hydrocarbon hydroxylase, glutathione-S-transferase (GST) and glutathione reductase (GR) increased after treatment with these two vitamins. Administration of vitamins E and A do not provide significant longterm protection against TCDD-induced lethality although they can prevent TCDD-induced microsomal lipid peroxidation as determined by the thiobarbituric acid assay method.     

The prevalence of coagulation abnormalities in hospitalized patients receiving lipid-based parenteral nutrition

BACKGROUND: Vitamin K is not a component of the multivitamin preparation added to parenteral nutrition (PN) solutions, and hospitalized patients receiving parenteral nutrition support are at risk of developing vitamin K deficiency. METHODS: In this study, 84 consecutive patients receiving PN were followed up prospectively to determine the incidence of a raised international normalized ratio (INR). All patients received lipid in their PN, which contains approximately 30 microg of vitamin K/100 mL. RESULTS: Patients were followed up for the course of PN or up to 4 weeks if they needed longer total parenteral nutrition. A raised INR compared with baseline developed in 3.6% of patients. All elevations were mild, and no patients developed clinical bleeding. CONCLUSIONS: It may be unnecessary to routinely supplement patients with vitamin K if they are receiving a lipid emulsion containing significant amounts of vitamin K. For patients receiving warfarin therapy, it will be important for nutrition support services to be aware of the vitamin K content of the lipid emulsion they are using as patients receiving a multivitamin preparation containing vitamin K and lipid emulsion may receive increased amounts of vitamin K, which could lead to warfarin resistance.