Stability of thiamin in parenteral nutrition solutions

Since the vitamin thiamin is sensitive to degradation in the presence of stoichiometric concentrations of sulfite ions, the stability of thiamin in parenteral nutrition solutions containing sulfite as an antioxidant and preservative has been questioned. The usual clinical practice of mixing amino acids, dextrose, and other solutions for administration in total parenteral nutrition significantly dilutes the concentration of sulfite. We have measured the thiamin concentration in total parenteral nutrition solutions sampled from containers after administration to patients. We have also determined the time course of thiamin degradation in solutions containing two concentrations of sulfite. Thiamin content exceeded labeled amounts in total parenteral nutrition bags containing amino acid, dextrose, and multivitamin solutions. However, when multivitamins were added directly to amino acid solutions containing 0.1% (9.6 mM) sulfite, significant degradation occurred by 5 hr. Thiamin was stable for at least 22 hr when added to total parenteral nutrition solutions containing less than 0.05% (4.8 mM) sulfite.     

Infection control of parenteral nutrition solutions

Microbial contamination of parenteral nutrition solutions is a preventable cause of in patients receiving nutrition support. The components of the parenteral nutrition solutions have variable microbial growth potential. Crystalline amino acid and dextrose solutions are poor growth media for bacteria but may support fungal growth. Lipid emulsions provide an excellent medium for growth of bacteria and fungal species. Total nutrient admixtures will support microbial growth better than standard parenteral nutrition solutions will but less well than will lipid emulsion alone. Control of infection related to contaminated infusate depends on compounding procedure, quality control, appropriate storage, and procedures to prevent in-use contamination. Guidelines are presented for the preparation and administration of parenteral nutrition infusates that will minimize microbial contamination.     

Determinants of insulin availability in parenteral nutrition solutions

BACKGROUND: Management of hyperglycemia in patients receiving parenteral nutrition (PN) often includes the addition of regular insulin to the PN solution. A literature review has shown insulin availability in such solutions to range from 10% to 95%. This discrepancy in availability may be due to differences in the composition of the PN solution, the final concentration of insulin, or the assay method used to determine insulin concentrations. The purpose of this study was to evaluate insulin recovery from a standard PN solution used at our medical center. METHODS: Solutions were manually prepared in our pharmacy according to standard practice. Multivitamins and trace elements were added to 1 of 2 L of solution each day. Each of 3 simulated patients received 2 L of solution per day for 3 consecutive days. Samples from each bottle were drawn at baseline, 1 hour after the start of infusion, and 1 hour before the end of infusion and were subsequently analyzed for immunoreactive insulin levels by radioimmunoassay. RESULTS: Recovery of insulin from solutions containing multivitamins and trace elements was much greater (95%) than from those without (5%). CONCLUSIONS: The presence of multivitamins and trace elements is a major determinant of insulin availability in PN solutions. Additional research is necessary to determine the mechanism mediating this effect and to assess its clinical significance.     

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.     

Chromium content of total parenteral nutrition solutions

Chromium (Cr) present as contaminant was analyzed by flameless atomic absorption spectrometry in a variety of commercially produced solutions and additives commonly used in total parenteral nutrition (TPN) formulas. Total Cr likely to be administered unintentionally per day was estimated both by summing the Cr in appropriate volumes of each solution required for preparation of standard TPN formulas and by analyzing complete TPN solutions. Storage of TPN solutions in plastic bags for 14 days did not affect Cr concentrations. The amounts ranged from 2.4 to 8.1 micrograms/day for a high glucose formula and 2.6 to 10.5 micrograms for a high lipid formula. Amino acid solutions, especially when containing phosphate, or with phosphate salt additives and with lipid emulsions accounted for approximately 85 to 90% of the Cr found.     

Protecting solutions of parenteral nutrition from peroxidation

BACKGROUND: Light exposure induces the generation of peroxides in solutions of total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell, in tissue, and in isolated organs. To decrease the infused peroxide load and to protect the quality of the parenteral nutrients, we tested the photoprotective properties of different infusion sets. METHODS: Solutions of fat-free TPN and all-in-one total nutrient admixture (TNA) were run through sets of bags (clear and covered) and tubings (clear and colored: black, orange, and yellow) offering different levels of protection against light. Peroxide levels were determined by ferrous oxidation of xylenol orange, thiol functions by the 5,5,-dithiobis(2-nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy. RESULTS: Protection of only the bag had little effect on peroxide generation. In fat-free TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times higher when run through clear compared with colored tubings. When exposed to phototherapy or in the presence of lipids, peroxides were two to three times higher with the clear compared with the black tubing; meanwhile, orange and yellow tubings offered varying levels of protection related to their light-absorbing properties. Colored tubings offered a greater protection against the disappearance of thiol functions. CONCLUSIONS: Covering bags and using orange and yellow tubings may be a practical solution to reduce infused peroxide loads from about 400 to 100 microM. This is especially relevant in patients with an immature or a compromised antioxidant capacity or when phototherapy or preparations of TNA are used.     

Current total parenteral nutrition solutions for the neonate are inadequate

The amino acid requirements of the parenterally fed neonate are poorly defined. Newborn infants are at risk for amino acid deficiency and toxicity, due to lack of small intestinal metabolism and metabolic immaturity. We discuss recent evidence that identifies inadequacies of commercial amino acid solutions with respect to the balance and quantity of aromatic amino acids, and sulphur amino acids. We present data demonstrating that impaired small intestinal metabolism (or lack of first pass metabolism) alters the whole body requirement for methionine, threonine, and arginine, and discuss the potential adverse effects of excess or inadequate parenteral amino acid intake.     

The stability of L-glutamine in total parenteral nutrition solutions

An assessment was made over a period of 14 days of the rate of glutamine degradation in different intravenous solutions kept at 22-24 degrees C, 4 degrees C, -20 degrees C and -80 degrees C. At room temperature (22-24 degrees C) degradation rates in mixed parenteral nutrition solutions and aminoacid/dextrose solutions ranged from 0.7-0.9%/day, in Perifusin 0.6%/day, and in dextrose alone as low as 0.15%/day. At 4 degrees C, glutamine degradation was <0.1-0.2%/day in all solutions examined, at -20 degrees C it was minimal (<0.04%/day) and at -80 degrees C, it was undetectable. Glutamine degradation was found to be associated with the formation of equimolar quantities of ammonia. No glutamate formation was detected. It is concluded that it is possible to store glutamine in parenteral nutrition solutions kept at 4 degrees C, with about 2% loss over a period of 14 days. The degradation is sufficiently slow to consider the use of intravenous glutamine in nutritional therapy.     

Availability of insulin from total parenteral nutrition solutions

Insulin is frequently required in total parenteral nutrition (TPN) solutions to control hyperglycemia. The purpose of this study was to evaluate the recovery of human insulin from standard TPN solutions with and without lipids and from TPN solutions with specialized amino acid formulations and to compare it to the insulin recovery from normal saline. All solutions were mixed in currently utilized PVC-free bags (ethylene vinyl acetate) and drained through PVC-containing tubing. Human insulin (Humulin-R) was spiked with 125I-labeled insulin and then added in concentrations of 10, 25, and 50 units to 1-liter bags containing 39-g amino acids (10% Freamine-III; or 6.9% Freamine HBC; or 8% Hepatamine), 257-g dextrose, electrolytes (Hyperlyte-R), 1000 units of heparin, MVI-12, and MTE-5 Concentrate. Alternate sets of bags contained 125 ml of 20% Intralipid and an appropriate amount of sterile water to keep the final volume at 1 liter. Actual clinical conditions of preparation, storage, and administration were simulated in this in vitro experiment. Multiple samples were collected during the 8-hr infusion period directly in gamma counter vials. All experiments and assays were done in triplicate. Our findings indicate that human insulin availability in TPN solutions is much higher (90%-95%) than the 50% suggested in the literature. Insulin recovery was not appreciably altered by adding lipids or by using Freamine HBC. Insulin recovery from TPN solutions was significantly reduced if they contained Hepatamine (87% and 88%, p less than 0.05) as compared to Freamine (90% and 94%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Trace metal profile of parenteral nutrition solutions.

Zinc, copper, iron, magnesium, and chromium were analyzed in commercially prepared total parenteral nutrition solutions of amino acid/protein hydrolysate, dextrose, lipid, and water from several manufacturers. Concentrations of each varied with both the manufacturer and the solution lot number, with the greatest differences observed for zinc (0.026 to 4.04 mg/liter) and iron (0.025 to 1.370 mg/liter). Since the consequences of prolonged total parenteral nutrition with trace-metal-deficient solutions are dependent upon the physical state of the patients, the duration of hyperalimentation and problems associated with trauma, it is recommended that the endogenous concentrations described be supplemented as needed for each patient. This need is difficult to determine, however, because little is known about the clinical effect of any trace-metal-deficiency state developing in patients receiving long-term total parenteral nutrition.     

Supplementation of total parenteral nutrition solutions with ferrous citrate

Daily infusion of a total parenteral nutrition (TPN) formulation containing 1 liter of 5.5% Travasol provides less than 0.1 milligrams of iron. By comparison, a formulation which includes a liter of 10% Travamin provides 2 milligrams of iron per day. To meet iron requirements in patients infusing formulations containing Travasol, iron was added as ferrous citrate. In in virto experiments, 74% of this iron was available to transferrin. In seven patients in whom in vivo availability was tested by red cell incorporation, the mean availability was 81%. Ferrous citrate is recommended as a safe, effective additive to TPN solutions for adult patients requiring iron supplements.     

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.     

Piggyback compatibility of antibiotics with pediatric parenteral nutrition solutions

The compatibility of 28 parenteral antibiotics with a pediatric parenteral nutrition solution was tested using a piggyback injection technique. The parenteral nutrition solution, apparatus, and antibiotic doses simulated central venous administration to 5- and 30-kg patients. All antibiotics were injected into a running parenteral nutrition solution, distal to an in-line filter. After passing through a central venous catheter, immersed in a heated water bath, the effluent was collected, analyzed for pH, and visually inspected for precipitate formation. The effluent was not evaluated for the presence of microscopic precipitates. When given as piggyback injections, five of the 28 antibiotics increased the pH of the original parenteral nutrition solution. These were ampicillin, cefamandole, cephalothin, cephradine, and oxacillin. Two of these, ampicillin and cephradine, produced a heavy visible precipitate, found to consist of calcium and phosphorus. The injections of certain antibiotics promote the formation of an insoluble calcium phosphate precipitate. When calcium and phosphate are present in a parenteral nutrition solution, a flush procedure is recommended when injecting antibiotics which increase the pH of the original parenteral nutrition solution.     

Particulate contamination in parenteral nutrition solutions: still a cause for concern?

OBJECTIVES: In consideration of a US Federal Drug Administration recommendation that all parenteral nutrition admixtures should be administered through an in-line filtration device, this observational study examined the number, size distribution, and sources of particulate contamination in parenteral nutrition admixture infusion systems. METHODS: Samples were drawn from the terminal connection of the infusion tubing before connection to the patient. The particles were sized and counted by optical microscopy and further investigated by electron microscopy and energy disperse spectroscopy. RESULTS: Large numbers of particles were found, and information gained about their possible origin. CONCLUSIONS: This study provides further support for the adoption of this Federal Drug Administration recommendation.     

Compatibility of parenteral nutrition solutions when mixed in a plastic bag

The administration of a single admixture of the components used in total parenteral nutrition has been considered more convenient and to give rise to less infection than the conventional regimen with separate infusions. The physico- chemical properties of several admixtures corresponding to commonly used regimens for complete parenteral nutrition have been studied. A 28 day toxicity study was carried out in the dog for one of these mixtures. It was concluded that Intralipid an be mixed with Vamin and dextrose solutions, supplemented with electrolytes, trace elements and vitamins provided that the admixtures are within certain defined ranges, prepared under strictly aseptic conditions and used within a limited time. Deviations from these ranges and component formulae should not be made without appropriate testing.     

Long-term stability of lipid emulsions with parenteral nutrition solutions.

The stability of the mixture of peripheral vein parenteral nutrition (PN) solution with 10% lipid emulsions (Intralipid or Lipofundin MCT) was tested during a prolonged period of refrigerated storage. The analysis included gross visual examination of the bottle, pH determination, and examination by electron microscope. The mixtures of fat emulsions with PN solution demonstrated no physical instability or pH alteration. Examination under electron microscope revealed no alterations after 4 wk, but the surface layer of fat globules was disrupted after 10 and 18 wk. This study demonstrates that complete nutritive mixtures can be prepared and stored in refrigeration for at least 4 wk before clinical use.     

Practice-based validation of calcium and phosphorus solubility limits for pediatric parenteral nutrition solutions

In an effort to maximize the precipitation-free delivery of calcium and phosphorus to neonates, Fitzgerald and MacKay published in 1986 the results of empirical determination of calcium-phosphate saturation curves for a number of parenteral nutrition (PN) solutions. The saturation curves generated from these investigations have been used to formulate thousands of PN solutions. The curves were developed testing only calcium and phosphate without other components added to PN solutions. The authors reviewed 38,019 PN orders from 2007-2010 and plotted the calcium and phosphate concentrations for each solution in relation to the published curves to assess the practical validity of the curves. The solutions reviewed were compounded using standard weight ranges for electrolytes, trace minerals, and vitamins. The solutions were evaluated for precipitation using standards for visual compatibility against a black and white background. There were no visual precipitates found in the 38,019 PN solutions. All calcium and phosphorus concentrations plotted below the precipitation limits predicted by the published curves despite a large range of concentrations of electrolytes and minerals. There has always been concern about extrapolating data from solubility curves that were developed empirically from a limited number of test solutions based on the few variables of calcium, phosphorus, amino acid concentration, and presence of cysteine HCl and/or fat emulsion. This experience validates the calcium and phosphorus solubility limits represented by published curves. Moreover, the findings support the concept that principal variables governing calcium and phosphorus precipitation in PN solutions are calcium, phosphorus, amino acid concentrations, temperature, and pH.