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)     

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.     

Determinants of quality of life in home parenteral nutrition

PURPOSE OF REVIEW: To highlight the most important and salient articles regarding home parenteral nutrition and quality of life published within the last 3 years. RECENT FINDINGS: In recent years, quality of life research in home parenteral nutrition has highlighted the need for a therapy-specific validated questionnaire. Several papers suggest a greater psychological input is required to better understand and evaluate this patient population. Issues surrounding the use of home parenteral nutrition in malignancy have arisen, prompting discussion on ideal timing and candidacy for home parenteral nutrition. Intestinal transplantation is evolving and improving, making it a possible alternative to home parenteral nutrition. Earlier referral is suggested as late referral can result in poorer outcome. SUMMARY: Home parenteral nutrition is a life-sustaining therapy for individuals with intestinal failure. There is now a relatively large amount of research into the quality of life in this population, but more focused measurements (in the form of validated therapy-specific questionnaires) are required to answer questions relating to cancer and intestinal transplantation.     

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.     

Arsenic species in solutions for parenteral nutrition

BACKGROUND: In spite of its high toxicity, arsenic is a common contaminant in pharmaceuticals. This is stated by pharmacopoeias' monographs where it is not generically included with other heavy metals, but has its own specifications. Arsenic should not exceed 0.1 mg/L in most pharmaceutical products for IV administration. This limit, however, was established without taking into consideration the specific arsenic species which contribute to this amount. In this work, the presence of arsenite and arsenate species in solutions of amino acids, salts, vitamins, and lipids commercialized for IV administration was investigated. METHODS: The measurements were done by hydride generation atomic absorption spectrometry. RESULTS: The results showed that all commercial formulations contain both arsenic species in some level; however, the total arsenic content exceeded the allowed limit in only a few samples. Calcium gluconate, sodium bicarbonate, heparin, and vitamin solutions were the most contaminated, presenting total arsenic concentration ranging from 62 to 249 microg/L. The most important finding, however, was the different ratios As(V)/As(III) among the formulations. Whereas practically only As(V) was found in ampoules containing water for injection and salt solutions (NaCl, KC1, phosphates), As(III) predominated in solutions of vitamins, gluconate, and glucose. As these are reducing substances, we investigated the possibility of their reaction with As(V) and its conversion into As(III). The heating of As(V) in the presence of gluconate, glucose, ascorbic acid, methionine, isoleucine, sodium chloride, and pure water, in autoclave for 15 minutes, showed that, whereas no As(III) was found in pure water and sodium chloride solution, approximately 50% of As(V) was converted into As(III) in the remainder of the solutions. Conclusions: The results showed that As(V), the main species in these formulations, may be converted into As(III), depending on the presence of reducing substances among the formulation constituents.     

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.     

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.     

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.     

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.     

Postoperative parenteral nutrition while proactively minimizing insulin resistance

OBJECTIVE: We compared the metabolic effects of postoperative total parenteral nutrition (TPN) and hypocaloric glucose after treatment with oral carbohydrates preoperatively and epidural anesthesia to proactively minimize postoperative insulin resistance. METHODS: Thirteen patients undergoing colorectal resections were given oral carbohydrates preoperatively and epidural anesthesia and randomized to TPN or hypocaloric glucose during and after surgery. Insulin sensitivity (hyperinsulinemic clamp [0.8 mU x kg(-1) x min(-1)], normoglycemic clamps [4.5 mM]), and glucose kinetics (6,6(2)H2-D-glucose), were studied before and on postoperative day 3. Indirect calorimetry was performed and nitrogen excretion in urine was measured. Values are presented as mean +/- standard deviation. Analysis of variance, planned comparison, and Bonferroni's correction were used for statistical analysis. RESULTS: Three days after surgery insulin-stimulated whole-body glucose disposal decreased by 24 +/- 11% versus 28 +/- 23% in patients receiving TPN and hypocaloric glucose, respectively (P < 0.05 for both, not significant between groups). Endogenous glucose production during insulin stimulation was increased only in the glucose group after surgery (P < 0.05 versus before). After surgery, insulin-stimulated glucose oxidation was higher after treatment with TPN, whereas fat oxidation was lower (P < 0.05 for both versus glucose treatment). Fat oxidation increased in the glucose group at basal after surgery (P < 0.05 versus before). Nitrogen balance was less negative after treatment with TPN (P < 0.01). CONCLUSIONS: Treatment with TPN does not seem to improve postoperative peripheral insulin sensitivity in patients with minor insulin resistance after pretreatment with preoperative carbohydrates and perioperative epidural anesthesia. Hypocaloric nutrition results in changes in substrate utilization and nitrogen balance resembling starvation, whereas TPN attenuates these changes.     

Use of separate insulin infusions with total parenteral nutrition

The efficacy, safety, and cost effectiveness of treating total parenteral nutrition (TPN)-induced hyperglycemia with a continuous insulin infusion, separate from the actual TPN bottle, was evaluated. A patient was included in the study if his serum glucose was greater than 200 mg/dl at a TPN infusion rate of less than 75% of the calculated caloric goal. The insulin infusion was run into the central line with the TPN via a Y-connector. At the patient's caloric goal, the infusion was stopped and the insulin was added to the TPN bottle, after the glucose was in the 100-200 mg/dl range for 24 hr. Sixteen patients including five known diabetics were studied, with data gathered retrospectively through chart review. It was estimated that 7.3 liters of TPN per patient were saved, compared to the amount used when insulin was added to newly prepared bottles of TPN each time a dosage change was required. In our institution, this amounts to a savings of $395.00 per patient (including charges for materials and an infusion pump for the insulin infusion). We conclude that separate insulin infusion is a reasonable and cost-effective alternative when treating glucose intolerance in patients receiving TPN.     

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.     

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.     

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.     

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.     

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.