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 photodegradation of vitamins A and E in parenteral nutrition mixtures during infusion

BACKGROUND & AIMS: Vitamins A and E are the most light-sensitive vitamins. Vitamin A is degraded by photolysis, while vitamin E degrades by photo-oxidation. The composition of the parenteral nutrition mixture and the container could therefore influence degradation during daylight administration. The aim of this study was therefore to determine the influence of fat emulsion and the type of bag on the photo-degradation of vitamins A and E in Parenteral Nutrition (PN) mixtures during simulated infusion in daylight. METHODS: Representative adult PN mixtures, with and without fat emulsion, were prepared. Samples for analysis were taken from infusates and each bag during simulated infusion. Degradation of vitamins A and E was determined by stability-indicating HPLC analysis. RESULTS: Results indicated that vitamin A loss proceeded rapidly during infusion, resulting in up to 80% loss in 6 hours, even with light protection of the bag. The presence of fat emulsion did not provide significant light protection. Vitamin E degradation was substantial if mixtures were prepared in EVA bags but was largely prevented if PN mixtures were compounded and stored in multi-layered bags. CONCLUSIONS: It is recommended that all PN bags should be light-protected during infusion in daylight. The use of multi-layered bags will prevent vitamin E losses during infusion.     

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 multilayered bags vs ethylvinyl-acetate bags on oxidation of parenteral nutrition

BACKGROUND: We evaluate the effects of multilayered bags vs ethylvinyl-acetate bags on peroxidate formation of various emulsions for all-in-one total parenteral nutrition solutions (TPN) during storage. METHODS: Twenty-four parenteral nutritions were prepared with 4 commercial i.v. lipid emulsions (Soyacal 20%, Grifols; Intralipid 20%, Fresenius-Kabi; Lipofundina 20%, Braun; and Clinoleic 20%, Clintex) and 2 different bags (multilayered [ML] bag, Miramed; and 1 ethylvinyl-acetate [EVA] bag, Miramed). Each kind of TPN was prepared in triplicate. Samples were taken at 3 different times: immediately after preparation (time 0), after 6 days at 4 degrees C and 48 hours at 37 degrees C (time 1), and finally after a total of 14 days at 37 degrees C (time 2). Oxidation of TPN was evaluated by analysis of hydroperoxides by ferrous oxidation-xylenol orange (FOX) reactive, lipoperoxides by thiobarbituric acid reactive species (TBARS), alpha-tocopherol by high-performance liquid chromatography (HPLC), and ascorbic acid and dehydroascorbic acid by HPLC. RESULTS: TPN admixtures in ML bag showed less oxidation evaluated by peroxide determination using FOX than EVA bag. Lipoperoxides by TBARS did not show significant differences between 2 bags. Ascorbic acid and dehydroascorbic acid disappeared in EVA bags at time 1. No important differences were found in alpha-tocopherol content. CONCLUSIONS: Multilayered bags minimize oxidation.     

The stability of thiamine in total parenteral nutrition mixtures stored in EVA and multi-layered bags

The compounding of complete total parenteral nutrition (TPN) mixtures into big bags with extended shelf-lives has been made more possible by the introduction of reduced gas permeable bags, using multi-layered plastic laminates. Since this produces a highly reduced chemical environment, the stability of thiamine; which degrades by reduction, may be compromised. It was the purpose of this study to investigate the degradation of thiamine at two different concentrations in TPN mixtures containing different commercial amino acid sources stored for extended periods in EVA or multi-layered bags. Results indicated that thiamine was unstable in mixtures containing Freamine III 8.5%, a metabisulphite-containing amino acid infusion, but was relatively stable in mixtures containing Vamin 14, Aminoplex 12 or Eloamin 15% as the amino acid source. Degradation of thiamine in Freamine III 8.5%-containing mixtures stored in multi-layered bags was more rapid than in EVA bags. Degradation rate was not greatly influenced by thiamine concentration. Results indicate that thiamine is stable in complete TPN mixtures for periods of at least 28 days in multi-layered bags, provided metabisulphite containing amino acid infusions are avoided. The shelf-life of complete mixtures containing Freamine III should be restricted to ensure patient receive minimum acceptable daily thiamine requirements.     

Administration of fat emulsions with nutritional mixtures from the 3-liter delivery system in total parenteral nutrition

A series of studies was performed to test the efficacy and safety of a parenteral lipid emulsion, Lipofundin S, when given as part of a complete nutritive mixture from the three-liter bag total parenteral nutrition (TPN) delivery system. In vitro stability studies with mixtures corresponding to high and low nutritional intakes showed the fat emulsion to be stable during refrigerated storage for at least 6 days. The clinical use of Lipofundin S in 3-liter TPN bags was studied in 39 consecutive patients requiring TPN, and there were no untoward side-effects. Nitrogen balance was maintained in patients with pancreatitis, those recovering postoperatively, and those with miscellaneous conditions. However, patients with multiple trauma remained in negative balance. The ability of sera, from patients on TPN to agglutinate Lipofundin S was compared to that from healthy controls, and acutely ill patients not on TPN. Patients on TPN showed a higher degree of in vitro creaming than acutely ill controls, and this may have been related to the severity of the underlying illness. These studies suggest that this parenteral lipid emulsion can be safely administered to patients requiring TPN when given from the 3-liter bag delivery system.     

Assessment of ascorbic acid stability in different multilayered parenteral nutrition bags: critical influence of the bag wall material

BACKGROUND: The recent development of multilayered bags has minimized ascorbic acid oxidation in parenteral nutrition (PN) admixtures. However, the gas-barrier property of multilayered bags depends on their plastic material. This study compared ascorbic acid stability in different multilayered bags under experimental conditions. METHODS: Oxygen permeability of a newly developed 6-layered bag (6-L) was compared with a highly mechanical-resistant 3-layered bag (3-L(R)) and a highly flexible 3-layered bag (3-L(F)) using gas chromatography. Ascorbic acid stability was assessed by iodine titration in bags filled with 2.5 L H(2)O and 40 g carbohydrates after setting residual O(2) content at < or =1 or > or =5 ppm. The effect of storage at 4 degrees C, 21 degrees C, and 40 degrees C on ascorbic acid stability was assessed over 48 hours in a complete PN admixture (ie, 330 g carbohydrates, 100 g lipids, 96 g amino acids and trace elements) using high-pressure liquid chromatography. RESULTS: Oxygen permeability was markedly reduced in 6-L bags (0.5 mL O(2) /m(2)/d) compared with 3-L(R) (150 mL O(2) /m(2)/d) and 3-L(R) (1500 mL O(2)/m(2)/d). Accordingly, ascorbic acid was more stable in 6-L bags (half-life [T(1/2)] = 16 days up to 40 degrees C) than in 3-L(R) (T(1/2) = 9 days at 4 degrees C, 47 hours at 21 degrees C and 29 hours at 40 degrees C) and 3-L(F) (T(1/2) = 15 hours at 4 degrees C, 10 hours at 21 degrees C, and 6 hours at 40 degrees C). During the first 6 hours after PN admixture compounding, an additive ascorbic acid loss of 4.6 +/- 0.5 mg/L/ppm O(2) occurred because of residual O(2) in the bag. CONCLUSIONS: The new combination of plastic layers and careful O(2) monitoring during the filling process allowed near to complete prevention of ascorbic acid degradation in multilayered PN bags during 48 hours, regardless of the storage temperature.     

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.     

Use of 5-micron filter in administering 'all-in-one' mixtures for total parenteral nutrition

An assessment was made of the stability of nine total nutrient admixtures (TNA) for total parenteral nutrition (TPN) and of Intralipid 20% filtered through a 5-micron filter. Mixture samples from 3-litre EVA plastic bags were obtained for tests 4 and 24 h after preparation, before and after filtration through a 5-micron filter during a period of 24 h. The filtered mixtures were collected in 3-litre EVA plastic bags and the contents of the filter were also examined. Stability parameters studied were pH, lipid globule size and visual signs of emulsion breakage. Used for assessment of lipid globule size were a light microscope and a Coulter Counter TA II, which measures particles from 1.4 microns to 43.8 microns in diameter. There were no physical signs of instability in any of the mixtures tested while they were being filtered and collected through the 5-micron filter. Examination of mixture samples prior to filtration and of filter contents revealed the presence of large fat globules, precipitates, solid particles and aggregates. Although these were trapped on the surface of the filter there was no slowing of the rate of flow of the mixture. These findings demonstrate the importance of using a 5-micron filter in delivering total nutrient mixtures in order to avoid the hazards posed by the presence of particles larger than 5 microns in size and show that its use does not affect stability.     

Chemical stability of selenious acid in total parenteral nutrition solutions containing ascorbic acid

Reduction of selenious acid (H2SeO3) to elemental Se by ascorbic acid was investigated in regard to the stability of selenite in total parenteral nutrition (TPN) solutions. [75Se] H2SeO3 (100 micrograms Se/liter) was incubated at 25 degrees C with pure ascorbic acid (100 or 500 mg/liter) or added to complete TPN solutions containing similar levels of ascorbate. The mixtures were subjected to thin layer electrophoresis at pH 5.3 to separate HSeO3- from Se degree. In complete TPN formulas, little or no reduction of HSeO3- to Se degree occurred over a 24-hr period, whereas complete reduction occurred with pure ascorbic acid. Further experiments showed that the amino acid component of the TPN formula was preventing the reduction of selenite, and that reduction of selenite by ascorbate did not occur in buffered solutions having a pH of 5 or greater. These results show that reduction of selenite is strongly influenced by pH. At the concentrations of H2SeO3 and ascorbic acid commonly used, reduction to elemental Se is unlikely to be a practical problem in TPN solutions in the near-neutral pH range.     

Stability of ascorbic acid in a standard total parenteral nutrition mixture

We investigated the stability of ascorbic acid (AA) and the sum of AA plus dehydroascorbic acid (TAA) in a total parenteral nutrition (TPN) mixture that contained 1000 ml Vamin 14, 1000 ml glucose 30%, 500 ml Intralipid 20%, potassium phosphate, a multivitamin preparation (Cernevit) and trace elements. We used a spectrophotometer to measure AA and TAA. AA decreased from 42.2 (+/-0.9) mug/ml to 6.8 (+/-0.2) mug/ml in 7 days. Over the same time the concentration of TAA decreased from 42.2 (+/-0.5) mug/ml to 35.9 (+/-0.6) mug/ml, i.e. 63.3 (+/-1.2)% of the original concentration. When the solution was stored in glass bottles and saturated with nitrogen or when trace elements were omitted, the concentration decreased by only 25.2 (+/-0.2)% and 23.8 (+/-1.6)% respectively over 7 days. The influence of oxygen, lipids, trace elements and underfilling the bag was also investigated. We conclude that it is acceptable to prepare these bags in advance and to store them for 7 days at 2-4 degrees C.     

Comparison of substrate utilization by indirect calorimetry during cyclic and continuous total parenteral nutrition

Five male adult home patients were studied in a randomized order under continuous (24 h/d) and nocturnal cyclic (15 h/d) isocaloric, isonitrogenous total parenteral nutrition (TPN). They received 2626 +/- 265 total kcal/d as 60% dextrose and 40% lipids; the 3-h lipid infusion was followed by the dextrose amino acid infusion on both regimens. Substrate oxidation was measured by indirect calorimetry during four periods on the fourth day of each regimen. During cyclic TPN net lipogenesis occurred with a nonproteic respiratory quotient (npRQ) greater than 1 during dextrose amino acid infusion followed by net lipolysis with an npRQ less than 1 during the nonnourishing phase. In contrast, during continuous TPN net lipogenesis persisted with an npRQ greater than 1 over the 21 h of dextrose amino acid infusion. During the 3-h lipid infusion, fat oxidation was observed during both regimens but was more pronounced during cyclic TPN (p less than 0.05). As a consequence, 24-h lipid oxidation was higher and 24-h dextrose utilization lower during cyclic vs continuous TPN (p less than 0.05). These results suggest that cyclic TPN when alternating between substrate storage and oxidation, mimics the physiological pattern of oral feeding.     

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)     

Tissue storage of vitamins A and E in rats drinking or infused with total parenteral nutrition solutions

The total parenteral nutrition (TPN) rat and its sham-operated control were used as a model to compare the metabolism and storage of vitamins A and E when they are administered intravenously or orally. Male Fisher rats were depleted of both vitamins for several months with a diet free of vitamins A or E, but containing retinoic acid for growth. TPN solutions containing aqueous dispersions of retinol, retinyl palmitate and dl-alpha-tocopheryl acetate were infused at 2.3 ml/h into the jugular veins of 10 TPN rats. Eight sham-operated control rats drank similar volumes from food cups. TPN rats received 115.3 +/- 4.5 (mean +/- SEM) micrograms of retinol equivalents and 2.2 +/- 0.2 mg of alpha-tocopherol equivalents per day; controls received 146.4 +/- 16.5 micrograms and 2.1 +/- 0.3 mg, respectively. After 7 days the animals were fasted overnight and killed. Plasma levels of retinol were 27.8 +/- 1.5 micrograms/dl for TPN rats, and 27.4 +/- 1.2 for controls. Plasma alpha-tocopherol was 1909 +/- 183 micrograms/dl for TPN rats and 1063 +/- 77 for controls. The only forms of the vitamins found in plasma after overnight fasting were unesterified retinol and unesterified alpha-tocopherol. Sham-operated control rats stored amounts of vitamins A and E similar to values reported in the literature for fed animals. TPN rats stored more of both vitamins than controls in liver, heart, and spleen, but not in testes. The enhanced liver vitamin storage by TPN rats did not appear to be due to a slight increase in lipid content. The results indicate that both vitamins A and E infused in TPN solutions maintain blood levels and are stored in tissues.     

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.     

Trace element contamination of total parenteral nutrition. 2. Effect of storage duration and temperature.

BACKGROUND: Patients who receive home total parenteral nutrition (TPN) frequently are supplied with solutions up to 30 days in advance of anticipated use. The purpose of this study was to determine the stability of trace elements relative to time and temperature conditions, in a typical adult TPN solution stored in a usual home environment by examining variations in delivery of intended trace elements and inadvertent trace element contamination. METHODS: Trace element concentrations were determined using inductively coupled plasma-mass spectrometry technology. The effect of the delivery apparatus, storage duration (36 hours or 30 days) after compounding, and storage temperature (4 degrees C or 20 degrees C) were examined. RESULTS: The delivery apparatus contaminated the delivered TPN solution with cobalt but did not alter trace elements formulated into the TPN solution. Storage duration and temperature significantly decreased three (Zn, Cu, and Mn) of the six trace elements formulated into the TPN solution. Higher temperatures and longer duration of storage accelerated this decrease. Boron, Al, V, Ti, Ba, Sr, and CO were the trace elements that appeared as contaminants during storage. Boron, Al, V, and Ti contamination decreased with higher temperatures and longer duration of storage. CONCLUSIONS: Longer storage duration and higher storage temperature progressively reduced the deliverable concentrations of trace elements specifically formulated into the TPN solution and also of those trace elements that were not formulated into the TPN solution but that appeared as contaminants.     

Thermogenesis from intravenous medium-chain triglycerides

Eighteen hospitalized patients dependent on total parenteral nutrition (TPN) were randomly enrolled into a prospective study comparing intravenous long-chain triglycerides (LCT) with a physical mixture of 75% medium-chain triglycerides (MCT) and 25% LCT. The TPN was given continuously as amino acids and glucose over 5 days with the respective lipid emulsion given intermittently during each day for 10 hr. Indirect calorimetry was measured on each patient before the lipid emulsion was administered in the morning and again 10 hr later near the end of the lipid infusion, on days 1, 3, and 5. Resting energy expenditure, VO2, VCO2, and calculated fat oxidation were shown to increase during MCT infusion but not during LCT administration, (resting energy expenditure 899 +/- 37 to 1085 +/- 40, compared with 978 +/- 23 to 976 +/- 39, kcal/m2 body surface area [BSA]/day, respectively, p less than 0.0002; VO2: 129.9 +/- 5.2 to 157.2 +/- 5.9, compared with 140.9 +/- 3.6 to 141.2 +/- 5.9 ml O2/min/m2 BSA, respectively, p less than 0.0005; and VCO2: 110.7 +/- 4.4 to 127.5 +/- 4.3, compared with 118.3 +/- 2.8 to 118.0 +/- 5.3, ml CO2/min/m2 BSA, respectively, p less than 0.0076; calculated fat oxidation 10.7 +/- 1.5 to 19.3 +/- 2.4, compared with 20.0 +/- 2.7 to 20.0 +/- 3.6, kcal/m2 BSA/hr, respectively, p less than 0.014). Respiratory quotient tended to fall with lipid infusion but did not change statistically. Body temperatures were unaltered by either fat infusion. It is concluded that TPN consisting of MCT causes an increased thermogenesis, most likely through increased fat oxidation, reflective of MCT's property as an obligate fuel. The increased thermogenesis occurs without an increase in body temperature.