Trace element contamination of total parenteral nutrition. 1. Contribution of component solutions.

BACKGROUND: Trace elements have been shown to contaminate total parenteral nutrition (TPN) solutions. METHODS: This study used the multi-elemental technology of inductively coupled plasma-mass spectrometry to demonstrate the extent to which trace elements were present in amounts above (ie, as contaminants) or below expected levels in eight TPN component solutions. RESULTS: Of the 66 trace elements scanned, there were 12 trace element contaminants in amounts >1 microg/L (zinc, copper, manganese, chromium, selenium, boron, aluminum, titanium, barium, vanadium, arsenic, and strontium) in the eight component solutions studied. Trace element contaminants were present in all solutions, and different trace elements contaminated the solutions at various concentrations. Component solutions of amino acid, potassium chloride, calcium gluconate, and sodium chloride contained the greatest numbers of trace element contaminants, whereas the lowest numbers were present in sterile water and magnesium sulfate. Interlot and intermanufacturer variations were apparent. Measured concentrations of trace elements in the multi-trace element additive solution also were higher than the labeled values. A comparison of the amounts of contaminated trace elements delivered by a typical TPN mixture relative to the amounts typically absorbed by the gastrointestinal tract indicates that the inadvertent delivery of trace elements from contaminated TPN solutions may be substantial. CONCLUSIONS: All eight components tested were contaminated with trace elements not intended to be present in the product, and similarly, the multi-trace element component contained trace elements either above or below that which the label claimed.     

Selected ultratrace elements in total parenteral nutrition solutions

Ultratrace elements are potentially essential (eg. boron, molybdenum, nickel, and vanadium) or toxic (eg, aluminum and cadmium) in humans. Long-term total parenteral nutrition (TPN) patients can inadvertently receive significant amounts of ultratrace elements present as contaminants in TPN solutions. We determined the intake of selected ultratrace elements from a standard TPN solution and compared it with the amount reported to be absorbed from food in normal subjects. Contamination of TPN solutions with ultratrace elements was widespread and variable. The daily intakes of Mo, Ni, V. and Cd from this contamination were comparable to the amounts reported to be absorbed through the gastrointestinal tract in normal subjects. Al intake was high; B intake was low, approximately 10% of the amount absorbed by normal subjects. Thus, TPN solutions are contaminated with significant amounts of ultratrace elements. The biological significance of the intravenous infusion of these ultratrace elements is unclear and requires further investigation, particularly in home TPN patients.     

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.     

Aluminium loading in children receiving long-term parenteral nutrition

Eight children on long-term, total parenteral nutrition (TPN) were found to have elevated aluminium (Al) levels in plasma (51 +/- 11 mug 1 1 ), urine (223 +/- 78 mug 24 h) and bone. The load of Al in TPN solution was 232 +/- 89 mug/day, and, among the different parenteral solution components high Al concentrations were found in amino-acids, calcium gluconate, potassium lactate, and trace elements, representing respectively 40%, 30%, 15%, and 10% of the total Al intakes. The authors conclude that children receiving long-term TPN have excessive Al intakes and are exposed to Al toxicity. The prevention of Al contamination requires careful control of the TPN components.     

Pulmonary deposition of calcium phosphate crystals as a complication of home total parenteral nutrition

A patient on home total parenteral nutrition (TPN) developed a diffuse granulomatous interstitial pneumonitis secondary to calcium phosphate deposition. Calcium and phosphorus concentrations in the TPN formula were not unusually high, indicating that other factors contributed to calcium phosphate crystallization. The effects of duration of storage of the TPN formulation, solution temperature, pH, and magnesium concentration on calcium phosphate precipitation are discussed.     

Supplementation of essential trace elements during total parenteral nutrition--effects on trace element-deficient rats

Thirty-one male SD rats, six weeks old, were fed a trace element-deficient diet for two weeks and then divided into three groups and maintained for 1 week as follows: group A with total parenteral nutrition (TPN) without supplementation of trace elements, group B with TPN supplemented with the following 5 trace elements ... iron, zinc, copper, manganese and iodine, and group C with a diet free of the above five trace elements. Another group of eight rats was fed a diet supplemented with the above five trace elements for three weeks as a control (group D). Feeding or TPN without supplementation of trace elements evoked microcytic hypochromic anemia and significant decreases in iron concentrations in plasma and tissues (groups A and C). Supplementation of trace elements in the TPN solution showed a tendency to cure anemia and a significant increase in the iron concentration in tibia (group B). Decreases in the zinc or copper concentrations in plasma and tissues during TPN without trace elements were prevented by supplementation of trace elements in the TPN solution (group B). The plasma zinc and copper concentrations correlated well with their levels in liver, kidney and tibia. Manganese deficiency was not recognized in this investigation (groups A and C), though supplementation of trace elements in the TPN solution increased tissue manganese concentration (group B). Feeding or TPN without supplementation of trace elements induced decreases in plasma triiodothyronine and thyroxine (groups A and C). Supplementation of trace elements in the TPN solution showed a tendency to increase plasma thyroxine (group B).(ABSTRACT TRUNCATED AT 250 WORDS)     

Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats.

OBJECTIVES: Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage. METHODS: Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry. Twenty-six male Fisher 344 rats were assigned to two groups (chow/NaCl = 8 and TPN = 18). TPN or NaCl was infused at a rate of 50 mL/d. After 14 d, serum, femurs, spine, liver, kidneys, brain, spleen, and testes were analyzed for heavy-metal deposition by using inductively coupled plasma mass spectrometry. Tissues were fixed in formalin, sectioned, and stained with hematoxylin and eosin, periodic acid Schiff, and Masson's trichrome stain. Kidneys were fixed in gluteraldehyde for ultrastructural examination with scanning electron microscopy. RESULTS: The predominant sources of contaminants in TPN were amino acids (Al, As, Cr, Ge, Pb, Sn), dextrose (As, Ba, Cr, Sn), Ca gluconate (Al), K2PO4 (Al), lipid emulsion (As, Sn), and vitamins (As). Significant variations in the level of contamination depended on TPN formulation and brand of constituents. In the kidney, Pb, Cr, and Mn concentrations were greater than in controls, although there was no correlation with serum creatinine. Hepatic Cr and Pb concentrations were greater in TPN rats, although there was no correlation with serum aspartate aminotransferase or total bilirubin. Splenic Ba, Cr, Ge, Pb, Mn, and Sn concentrations were greater in TPN rats. Only serum Cr concentration was significantly correlated with splenic concentration (r = 0.46, P = 0.04). Brain and serum Ba concentrations were significantly correlated (r = 0.60, P = 0.007). No significant correlations were observed between any other metal in serum and that metal's respective organ concentration. No increase in heavy-metal accumulation was seen in the femur, spine, or testis. There were no significant depositions of As, Cd, Hg, St, or V in any of the organs examined. Serum Al and Cr concentrations were significantly increased in TPN rats, although there was no correlation with tissue concentrations. No significant increases in heavy-metal concentrations in tissue or plasma were observed for any of the other metals measurable by inductively coupled plasma mass spectrometry. Histologically in the TPN group, 50% of the rats had mild to moderate hepatic steatosis and 33% to 50% developed renal morphologic abnormalities; brains and spleens remained histologically normal. CONCLUSIONS: We found significant heavy-metal contamination of TPN solutions, and this contamination can lead to organ deposition and subsequent histologic abnormalities.     

Naturalized salmonid populations occur in the presence of elevated trace element concentrations and temperatures in the Firehole River, Yellowstone National Park, Wyoming, USA

We investigated the effects of geothermally influenced waters on the distribution of rainbow trout, Oncorhynchus mykiss, and brown trout, Salmo trutta, in the Firehole River and its tributaries in Yellowstone National Park (WY, USA) from June 1997 to June 1998. Geothermal features in the Firehole River basin elevate mineral content and temperature in portions of the river and its tributaries. We found concentrations of boron and arsenic to be elevated in geothermally influenced areas compared with upstream sites. Boron concentrations occasionally exceeded 1,000 microg/L, a proposed limit for the protection of aquatic organisms. Arsenic concentrations occasionally exceeded 190 microg/L, the chronic ambient water quality criterion. Temperatures in geothermally influenced sites ranged up to 30 degrees C and were consistently 5 to 10 degrees C higher than upstream sites unaffected by geothermal inputs. Rainbow trout occurred at sites with elevated concentrations of boron, arsenic, and other trace elements and elevated water temperatures. Rainbow trout inhabited and spawned at sites with the most elevated trace element concentrations and temperatures; however, brown trout were absent from these sites. Water temperature may be the major factor determining brown trout distributions, but we cannot exclude the possibility that brown trout are more sensitive than rainbow trout to boron, arsenic, or other trace elements. Further investigations are needed to determine species-specific tolerances of boron, arsenic, and other trace elements among salmonids.     

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.     

Total parenteral nutrition. A brief review.

The ideal solution for total parenteral nutrition (TPN) should contain nutrients equivalent to those of a well balanced, oral diet. With that goal in mind, available solutions usually provide adult patients with approximately 3,000 ml. solution daily, which supply about 12 gm. nitrogen and 2,400 kcal, with vitamins and minerals added as required. (Infants require relatively greater amounts of fluids and calories per kilogram.) The most critical concern in TPN is that of fluid and electrolyte balance, which varies with the patient. In this paper, the composition of four commercial TPN solutions is tabulated, as are recommendations for trace elements and vitamins which should be included.     

Essential trace element provision to patients receiving home intravenous nutrition in the United Kingdom

The methods of provision of essential trace elements to patients receiving long-term home intravenous nutrition in the U.K. have been reviewed and their trace element status has been assessed. Over a 2 year period, 57 patients based on 15 hospitals throughout the country were studied. Although biochemical abnormalities of trace element status were frequent, related clinical complications were apparently rare. Zinc provision from commercial preparations generally required further supplementation. Copper requirements were variable. Manganese provision from trace element mixtures and chromium provision from contaminants of other parenteral nutrient solutions were excessive in many cases. Aluminium contamination is not significant in the nutrient solutions currently used in the U.K. The most common depletion state is for selenium which should probably be provided on a routine basis. The clinical consequences of long-term under- or over-provision of trace elements by the intravenous route requires further study.     

Vancomycin stability in heparin and total parenteral nutrition solutions: novel approach to therapy of central venous catheter-related infections.

To facilitate therapy of central venous catheter-related Gram-positive bacterial infection in patients who require total parenteral nutrition (TPN) therapy, we studied the stability of vancomycin in a commonly used TPN solution (V-TPN) at final concentrations of 0.5 mg/mL and 1.0 mg/mL and in heparin (100 U/mL in 0.9% NaCl) at 25 micrograms/mL (V-H). Vancomycin concentrations in V-TPN and V-H after storage at 4 degrees C over 35 and 14 days, respectively, were stable (within 10% of the prestorage vancomycin concentration). After 14 days at 4 degrees C heparin activity in V-H solution was 100 +/- 4% of that noted initially. Vancomycin remained stable (100 +/- 6% of the original vancomycin concentration) when the previously refrigerated V-TPN was held for an additional 24 hours at 22 degrees C. When the previously refrigerated V-H was held for an additional 24 hours at 37 degrees C, vancomycin concentrations decreased to 78 +/- 9% of the baseline concentrations (p less than .001). The stability of vancomycin in this TPN solution allows the daily dose of vancomycin to be mixed with the solution and then infused over 10 hours. As shown with pharmacokinetic modeling, this form of therapy will achieve serum vancomycin concentrations within the therapeutic range throughout a 24-hour period. The relative stability of vancomycin in a heparin line-flush solution allows vancomycin concentration in the lumen of the catheter to be maintained at greater than or equal to 15 micrograms/mL during the interval between catheter flushing and the subsequent TPN infusion. A simplified method of administering vancomycin to patients receiving concurrent TPN is possible.     

野马追的微量元素研究

测定了野马追各部位 (花、叶、茎、根 )所含微量元素的种类和含量 ,结果表明 :野马追中含有丰富的微量元素 ,主要以 Fe、Al、Si为主 ,其次为 Sr、Ti、Mn、Ba,再次为 Zn、B、Pb、V、Cu。九月份采收的野马追全草的微量元素的含量普遍高于十一月份采收的药材。为野马追药效的进一步研究和开发利用提供了新的科学依据     

Factors affecting the stability of L-glutamine in solution

The degradation rate of L-glutamine in water, various buffers, and intravenous solutions was assessed over a period of 2 weeks. Measurements were made at various temperatures (22-24 degrees C, and 4 degrees C and -80 degrees C) and pH, and also in the presence and absence of light and oxygen (intravenous solutions only). At 22-24 degrees C, the degradation rate of glutamine was variable depending on the type of solution used (0.23% in water pH 6.5; 0.22% in dextrose/water [15% w/v]; 0.8% in mixed total parenteral nutrition (TPN) solution), and on the pH, molarity and type of buffer used. The degradation rate was essentially unaffected by light and O(2). The degradation rate of L-glutamine in the intravenous solutions was less than 0.15%/day at 4 degrees C, minimal at -20 degrees C (<0.03%/day), and undetectable at -80 degrees C. Glutamine degradation resulted in the equimolar formation of ammonia and no associated formation of glutamate. It is concluded that (a) glutamine degradation in solution is variable due to the effect of physico-chemical factors, and (b) glutamine degradation in TPN solutions is sufficiently slow, especially during storage at 4 degrees C or below, to consider its inclusion in such solutions, for clinical use.     

Determination of trace elements (Cu, Zn, Mn, Pb) and magnesium by atomical absorption in patients receiving total parenteral nutrition

OBJECTIVE: We measured the serum levels of four trace elements (Cu, Zn, Mn, Pb) and Mg in surgical patients receiving total parenteral nutrition (TPN). The clinical implications and the results are discussed. METHODS: Two groups of patients were studied: the first group (n = 40) was our study group and the second (n = 40) was the control group. Four measurements of each trace element (TE) in blood serum were carried out: one before initiating TPN, one 24 h after, one 3 d later, and the last one immediately after discontinuing TPN. Each measurement was repeated twice. The Perkin-Elmer atomic absorption spectrophotometer (model 2380) with furnace graphite HGA-300 was used to measure the TE levels and an acetylene flame was used to measure the Mg levels. RESULTS: Levels of all the TEs, except Pb, were lower before the administration of TPN compared with the control group (P < 0.05). The levels of TEs during and immediately after TPN were generally lower in comparison with the initial measurement before the administration of TPN. CONCLUSION: The results of this study suggest that it may be necessary to 1) add Cu, Zn, Mn, and Mg to the parenteral nutritional solution and 2) follow the fluctuations in serum levels during the administration of TPN.     

Growth responses of an estuarine fish exposed to mixed trace elements in sediments over a full life cycle

Hatchling Cyprinodon variegatus were raised in the presence or absence of sediments contaminated with mixed trace elements to examine lethal and sublethal bioenergetic effects (metabolic rate, lipid storage, growth, reproduction) over a full life cycle (>1 year). Contaminated sediments were derived from a site receiving coal combustion residues (CCR) and were elevated in numerous trace elements including Al, As, Ba, Cd, Cu, Se, and V. Exposures were conducted at two levels of salinity (5 and 36 ppt) to examine the potential interaction of this variable with contaminants. Salinity had no effect on responses measured. Over the course of the study, fish exposed to contaminated sediment accumulated several CCR-related trace elements, including As, Cd, Se, and V. There were no differences in fish survival for contaminated sediment treatments and uncontaminated sediment treatments, nor were there differences in metabolic expenditures. However, growth, male condition factor, and storage lipid content in females were reduced due to contaminant exposure. No significant effects on fecundity or the proportion of females that were gravid at the end of the study were observed, yet females raised under control conditions produced 12% larger eggs than did females raised on contaminated sediments. During the presumably most-sensitive early life stages, individuals were not noticeably affected by contaminants, but rather the effects of exposure became apparent later in life. Because many species inhabit contaminated areas for long periods of time, often encompassing the entire life cycle, exposures focused only on specific life stages may substantially underestimate the overall responses elicited by individuals.     

Sterility testing of home and inpatient parenteral nutrition solutions

The microbial contamination rate was compared for parenteral nutrition solutions prepared by patients for home use and by pharmacy personnel for inpatient use. Phase I validated the Ivex 0.22-micron inline filter as a tool for microbiological testing by inoculating small numbers of organisms in 5% dextrose injection and testing for recovery. Phase II validated the same method for determining microbial contamination of total parenteral nutrition (TPN) solutions. Phase III compared inpatient and home TPN microbial contamination rates using the methodology validated in phase II. Test organism inocula used in phase I and II were Candida albicans, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes. All contaminated solutions in phase I showed visual turbidity within 48 hr, and all test organisms were recovered and identified. All phase II-contaminated TPN solutions showed visual turbidity after 96 hr, and all test organisms were recovered and identified. One hundred postinfusion TPN samples were collected randomly during phase III from inpatient parenteral nutrition patients. Six patients and two hospitals participated in the study. None of the 44 home parenteral nutrition samples and none of the 56 inpatient TPN samples developed visible turbidity. Subcultures of each sample on blood agar were negative for microbial growth. This described methodology offers an effective means to establish contamination rates of parenteral nutrition solutions after administration.     

Evaluation of glyphosate drift and anthropogenic atmospheric trace elements contamination by means of lichen transplants in a southern Italian agricultural district

Ecophysiological biomarkers and atmospheric contamination due to glyphosate and trace elements were monitored in a southern Italian agricultural district by means of transplanted thalli of the lichen Pseudevernia furfuracea. Glyphosate exhibited a significant geographical pattern (east side?>?west side) and a drift source area equal to 32% of the monitoring sites. Moreover, based on the surface area of the study area and a wind quantitative relationship (WQR) with glyphosate thalli concentrations, our data support the idea that pesticide drift extends over an area of several square kilometers. Of the eight elements preliminarily classified as enriched, four were considered prevalently of geogenic origin (Al, Ti, Ni, Co) and four of anthropogenic origin (Cu, Mn, Sn, Sb), although only Sb and Cu passed rigorous statistical testing supporting a real difference from pre-exposure levels. The contribution of local sources was evaluated based on the relative increase of Cu, Mn, Sb, and Sn versus Ti. Cu and Mn were associated mainly with a biomass power plant (BPP), with Cu showing extremely high levels of contamination involving 20% of the monitoring sites. Sb and Sn were associated with spatial variation of the traffic rate. The mycobiont and photobiont showed an evident zonation of the levels of their physiological parameters, with oxidative stress being significantly associated with both the biomass power plant and Cu/Ti. Our results suggest that croplands are potentially exposed to various hazards: over-exposure to pesticides due to drift processes, diffuse low traffic levels promoting Sb enrichment, and acute Cu pollution affected by BPP emissions.     

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.