Doubling calcium and phosphate concentrations in neonatal parenteral nutrition solutions using monobasic potassium phosphate

BACKGROUND: Premature infants require high intakes of Ca and P to mimic fetal accretion rates. With the current phosphate salt used, adequate amounts cannot be provided due to the precipitation of Ca and P in TPN solutions. OBJECTIVE: To compare monobasic potassium phosphate (monobasic regimen) and monobasic plus dibasic potassium phosphate (dibasic regimen) on calcium phosphate solubility in 5 amino acid products, and to determine whether solubility differences observed in these products can be explained by buffering capacity. METHODS: TPN solutions were prepared according to standard clinical practice. The following amino acid products were used at 3% concentrations: Primene, Vamin N, TrophAmine, Aminosyn-PF, and Travasol. Dextrose 10%, standard electrolytes, heparin, vitamins and trace elements were added. Calcium (as gluconate) and phosphate (as monobasic or dibasic regimen) were added in one-to-one molar ratios from 0-45 mmol/L. Solutions were inspected macroscopically and microscopically for precipitation under three conditions: immediately, 24 h after preparation at room temperature, and 3 h later in a 37 degrees C water bath. Buffering capacity was determined for each amino acid product by titrating with standardized 0.1 M NaOH. RESULTS: Variations in Ca:P solubility and buffer capacity exist between amino acid solutions. With Primene and Vamin no macroscopic or microscopic precipitation was detected up to 45 mmol/L using monobasic regimen, compared to 25 mmol/L using dibasic regimen with Trophamine. Buffer capacity did not account for the solubility differences observed between the five amino acid products, which were related to the pH of the final solution. CONCLUSIONS: These data will allow clinicians to double the current concentrations of calcium and phosphate in neonatal TPN solutions using monobasic regimen. Although this is particularly relevant to situations when fluid intake is restricted, the effect of the acid load needs to be investigated in extremely low birth weight infants.     

Calcium and Phosphate Compatibility in Low‐Osmolarity Parenteral Nutrition Admixtures Intended for Peripheral Vein Administration

Background: Precipitation of calcium (Ca) and phosphate (P) salts can lead to potentially lethal outcomes, especially in low‐osmolarity parenteral nutrition (LO‐PN) formulations. Three concentrations of amino acids (AA) and 2 concentrations of calcium gluconate and sodium phosphate injections on the compatibility of Ca and P in LO‐PN admixtures were studied. Methods: Final AA concentrations of 1%, 2%, or 3% (n = 3) and 5% glucose (G) were prepared with either 2.5 or 5 mmol/L (5 or 10 mEq) of Ca (n = 2) and 15 or 30 mmol/L of P (n = 2) for a total of 12 base (3 × 2× 2) formulations. Triplicate bags of each were analyzed for subvisible micro‐precipitates using the light obscuration (or extinction) method for particle counts per milliliter (PC) in the size range of 1.8‐50 μm at 7 time intervals over 48 hours stored at 30°C ± 0.2°C. Visual evaluation was performed using a high‐intensity lamp against a black background for detection of macro‐precipitates. The pH of all 36 admixtures was measured at 0 and 48 hours. Any precipitated material was isolated and characterized by polarized light microscopy and infrared spectroscopy. Results: Of the 12 base LO‐PN formulations tested, those containing 1% and 2% AA with 5 mmol/L of Ca and 30 mmol/L of P showed significant increases in PC, and some resulted in visible dibasic calcium phosphate precipitation. Analyses of variance based on concentrations of AA, Ca, P, and time were highly significant independent variables for increases in the PC of potentially embolic particles, that is, sizes >5 μm (P < .0001). The lowest concentrations of Ca and P, 2.5 and 15 mmol/L, respectively, had significantly lower PC (P < .05) for all sizes compared with the other Ca and P combinations. Conclusions: LO‐PN admixtures (AA ≤ 3%; G = 5%) should not contain more than 2.5 mmol/L of Ca from calcium gluconate injection and no more than 15 mmol/L of P from potassium or sodium phosphates injection.     

The solubility of calcium and phosphorus in neonatal total parenteral nutrition solutions.

Precipitation of calcium phosphate in neonatal total parenteral nutrition (TPN) solutions remains a significant problem. Whereas numerous studies have attempted to establish guidelines for maximum concentrations of various combinations that can be mixed, differences in study design and reliance upon subjective visual assessment severely limit their applicability. The purpose of this study was to quantitatively determine calcium and phosphate compatibility in commonly used neonatal TPN solutions containing a final concentration of either 1 or 2% amino acids. The final dextrose concentration was 10%. Electrolytes, heparin, and pediatric vitamins and trace minerals were also added. Calcium gluconate (10%) and potassium phosphate (mono and dibasic) were added by calibrated micropipetors. Calcium concentrations ranged from 5 to 60 mEq/L and phosphate from 5 to 40 mM/L with a minimum of 84 combinations tested for each amino acid concentration. Calcium concentrations were measured in duplicate for each tested combination. Control solutions containing calcium but no phosphate were included to validate the assay methodology. All samples were stored at room temperature for 23.5 hours and then placed in a water bath at 37 degrees C for 30 minutes to simulate incubator conditions encountered during TPN infusion. Calcium determinations were then repeated and precipitation was judged to have occurred whenever calcium concentrations fell below 90% of the initial measured values. These data allowed plotting a calcium and phosphorus reference curve for TPN solutions containing 1 and 2% amino acids based on quantitative assessment. These reference curves should allow pharmacists to avoid compounding TPN solutions that will precipitate, thus saving considerable cost to the pharmacy and preventing complications.     

Efficacy of calcium glycerophosphate vs conventional mineral salts for total parenteral nutrition in low-birth-weight infants: a randomized clinical trial

To test the efficacy of calcium glycerophosphate (CaGlyP) vs the conventional mineral salts, calcium gluconate plus KH2PO4 + K2HPO4 (CaGluc + P), in promoting mineral retention, 72-h mineral balance, biochemical status, net acid excretion, and growth were assessed in 16 low-birth-weight infants receiving total parenteral nutrition (TPN) containing approximately 1.5 mmol Ca and P.kg-1.d-1 for 5 d. Net retentions of calcium (1.2 +/- 0.2 vs 1.0 +/- 0.2 mmol.kg-1.d-1, means +/- SD) and phosphorus (1.1 +/- 0.3 vs 0.8 +/- 0.3 mmol.kg-1.d-1) from CaGluc + P vs CaGlyP, respectively, were similar, as were retentions of magnesium and sodium, urinary pH, and net acid excretion. Plasma ionized calcium, inorganic phosphorus, alkaline phosphatase, and osteocalcin were normal and not different between groups. CaGlyP is as effective as CaGluc + P in promoting mineral retention and normal mineral homeostasis. However, at intakes of less than or equal to 1.5 mmol Ca and P.kg-1.d-1 from either mineral salt, retention represented only 60% and 45%, respectively, of the predicted intrauterine accretion for calcium and phosphorus. Larger intakes permitted by the more-soluble CaGlyP may be desirable for infants receiving TPN.     

Doubling Calcium and Phosphate Concentrations in Neonatal Parenteral Nutrition Solutions Using Monobasic Potassium Phosphate

Background: Premature infants require high intakes of Ca and P to mimic fetal accretion rates. With the current phosphate salt used, adequate amounts cannot be provided due to the precipitation of Ca and P in TPN solutions.

Objective: To compare monobasic potassium phosphate (monobasic regimen) and monobasic plus dibasic potassium phosphate (dibasic regimen) on calcium phosphate solubility in 5 amino acid products, and to determine whether solubility differences observed in these products can be explained by buffering capacity.

Methods: TPN solutions were prepared according to standard clinical practice. The following amino acid products were used at 3% concentrations: Primene, Vamin N, TrophAmine, Aminosyn-PF, and Travasol. Dextrose 10%, standard electrolytes, heparin, vitamins and trace elements were added. Calcium (as gluconate) and phosphate (as monobasic or dibasic regimen) were added in one-to-one molar ratios from 0–45 mmol/L. Solutions were inspected macroscopically and microscopically for precipitation under three conditions: immediately, 24 h after preparation at room temperature, and 3 h later in a 37°C water bath. Buffering capacity was determined for each amino acid product by titrating with standardized 0.1 M NaOH.

Results: Variations in Ca:P solubility and buffer capacity exist between amino acid solutions. With Primene and Vamin no macroscopic or microscopic precipitation was detected up to 45 mmol/L using monobasic regimen, compared to 25 mmol/L using dibasic regimen with Trophamine. Buffer capacity did not account for the solubility differences observed between the five amino acid products, which were related to the pH of the final solution.

Conclusions: These data will allow clinicians to double the current concentrations of calcium and phosphate in neonatal TPN solutions using monobasic regimen. Although this is particularly relevant to situations when fluid intake is restricted, the effect of the acid load needs to be investigated in extremely low birth weight infants.     

Calcium chloride and sodium phosphate in neonatal parenteral nutrition containing TrophAmine: precipitation studies and aluminum content

Objectives: The objectives were to determine concentrations of calcium chloride (CaCl) and sodium phosphate (NaPhos) that can be safely added to TrophAmine‐based parenteral nutrition (PN) and to measure aluminum (Al) concentrations in PN solutions containing CaCl and NaPhos vs those containing calcium gluconate (CaGlu) and potassium phosphate (KPhos). Methods: In study A, PN solutions containing varying amounts of TrophAmine, CaCl, and NaPhos were compounded and then evaluated visually for precipitation. In study B, Al concentrations were measured in PN solutions containing CaCl and NaPhos (S1), CaGlu and NaPhos (S2), or CaGlu and KPhos (S3). Results: Study A showed that a maximum phosphorus concentration of 15 mmol/L could be added to a solution containing 12.5 mmol/L of calcium without evidence of precipitation when the amino acid (AA) concentration reached ≥3 g/dL (3%). In study B, the mean (range) Al concentrations were S1 = 2.2 (1.9–2.4), S2 = 8.5 (7.8–9.3), and S3 = 11.7 (10.8–12.2) µmol/L (means of 6.0, 22.9, and 31.5 micrograms/dL, respectively). Conclusions: The data can provide a guide for compounding neonatal PN solutions containing TrophAmine, CaCl, and NaPhos. More studies are needed to determine the long‐term effects of substituting CaCl for CaGlu in PN solutions for neonates. Substituting CaCl and NaPhos for CaGlu and KPhos significantly decreases Al concentrations in PN and potential Al exposure of neonatal patients.     

Stability of parenteral nutrition admixtures containing organic phosphates

The use of organic phosphates to avoid calcium phosphate precipitation in parenteral nutrition mixtures has been proposed. The purpose of this study was to evaluate the stability of total parenteral nutrition admixtures containing glucose-1-phosphate or glycerol phosphate as the phosphate source over 3 days. Three parenteral nutrition admixtures, each containing glucose-1-phosphate (30.0 mmol), glycerol phosphate (31.4 mmol) or inorganic phosphate (30.0 mmol), and their corresponding aqueous phases were prepared in 3-L ethylene vinyl acetate plastic bags and infusion bottles, and stored at 5 +/- 1 degrees C or 22 +/- 3 degrees C without light protection. Physical stability analysis and sampling for chemical analysis was performed at 0, 24, 48 and 72 h. Aqueous phases were subjected to physical stability analysis, including pH measurement, visual inspection and nephelometry. Admixtures were subjected to physical stability analysis consisting of pH measurement, and evaluation of emulsion stability by visual inspection, degree of creaming, phase contrast microscopy, zone sensing technique and photon correlation spectroscopy. Chemical analyses of amino-acids, dextrose, triglycerides, phospholipids, Na, K, Cl, Mg, Ca, glucose-1-phosphate, glycerolphosphate and inorganic phosphate were performed. No precipitation was detected in any of the aqueous phases. Admixtures remained acceptable with respect to visual and microscopic appearance, mean droplet diameter and droplet size distribution. All nutrient concentrations assayed in the three admixtures remained constant over the study period. Total parenteral nutrition admixtures for adult patients containing glucose-1-phosphate or glycerolphosphate are physically and chemically stable for 3 days when stored under refrigeration or controlled room temperature without light protection.     

Optimisation des apports phosphocalciques dans les solutions de nutrition parentérale pédiatrique

Aim of the study. – In regards to the recurrent problem of the poor compatibility between calcium and phosphorus in paediatric parenteral nutrition admixtures, the aim of this experimental study was to compare the solubility of two phosphorus salts, namely the phosphate of potassium and the glucose-1- phosphate. Either one or the two of them were mixed together with calcium in parenteral nutrition solutions.Materials and method. – The solubility of the calcium phosphate was tested in 18 nutrient admixtures having different compositions (glucose: 200 g/L, aminoacids: 10 to 30 g/L, sodium: 30 mmol/L, potassium: 31 mmol/L, calcium: 12 to 25 mmol/L, phosphorus: 20 to 30 mmol/L, magnesium: 3 mmol/L, trace elements). The solubility was studied by visual observation and by measure of the particulate contamination and was rated according to the phosphorus salt used: phosphate of potassium, glucose-1-phosphate or these two salts mixed.Results. – Concentrations of 20 mmol of calcium and 30 mmol of phosphorus can be obtained in parenteral nutrition admixtures (containing 2% of amino acids) if the initial input of phosphorus is of the form of the GP. On the other hand, these concentrations are incompatible when using the phosphate of potassium because a precipitate occurs.The specifications of the european pharmacopeia are respected: for the particulate contamination, the number of particles with a diameter ≥ 10 μm is for all the tested admixtures lower than 5 particles/ml (standard: ≤ 25 particles/ml) if the GP represents at least 50% of the initial phosphorus input.Conclusion. – The results of this study confirm that the solubility of the phosphorus regarding to calcium is increased with the glucose-1-phosphate.The calcium and phosphorus needs for the children in parenteral nutrition can be covered while limiting the iatrogenic complications.     

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.     

Calcium glycerophosphate as a source of calcium and phosphorus in total parenteral nutrition solutions

Calcium glycerophosphate (CaGP) was tested as an alternative to calcium gluconate (CaGluc) and potassium mono- and dibasic phosphate (KPhos) as a source of Ca and P in total parenteral nutrition (TPN) solutions for piglets. Four-day-old piglets were infused for 7 days with a TPN solution that provided either 4.2 mmol Ca and 2.1 mmol P/kg/24 h as CaGluc and KPhos (the maximum quantities that can be provided using these sources), or 15.0 mmol Ca and 15.0 mmol P/kg/24 h as CaGP. Ca and P retentions were more than six times greater (p less than 0.01) in the piglets receiving CaGP (14.5 +/- 0.2 vs 2.2 +/- 0.3 mmol Ca/kg/24 h and 13.3 +/- 0.4 vs 2.4 +/- 0.1 mmol P/kg/24 h) (Mean +/- SEM). The ratio of Ca to fat-free dry weight, an indicator of bone mineralization, was significantly higher (p less than 0.05) in the humerus (174.8 +/- 2.2 vs 147.2 +/- 6.7) and femur (158.3 +/- 4.8 vs 130.1 +/- 7.8) in the CaGP group. This study showed that CaGP is efficiently used as a source of Ca and P in TPN solutions for piglets. The results suggest that the use of CaGP as the source of Ca and P in TPN solutions may prevent the development of the undermineralized bone seen in low-birth weight infants nourished intravenously.     

Glycero- vs glucose-phosphate in parenteral nutrition of premature infants: a comparative in vitro evaluation of calcium/phosphorus compatibility

In total parenteral nutrition (TPN) of premature infants, glycero- and glucose-phosphate have been recommended, and clinically used, because of their considerable compatibility with calcium. However, a systematic comparative in vitro assessment of the therapeutic potential and safety of these substances has not yet been provided. We investigated the stability of TPN solutions containing calcium-gluconate and glycero- or glucose-phosphate in high concentrations. Evaluation was performed by visual inspection, absorptiometry, light microscopy, measurement of pH, and determination of calcium concentration before and after microfiltration. Even under circumstances promoting precipitation of calcium and phosphate--such as body temperature, relatively high pH, and concentrations of calcium and phosphorus exceeding those necessary to provide intrauterine accretion rates, all but one of the examined TPN admixtures remained stable. Our data suggest that the use of glycero-phosphate, and particularly glucose-phosphate, together with calcium-gluconate, is an uncomplicated and safe procedure to administer simultaneously high amounts of calcium and phosphorus in TPN of premature infants.     

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.     

Maximizing Calcium and Phosphate Content in Neonatal Parenteral Nutrition Solutions Using Organic Calcium and Phosphate Salts

Background: The provision of high amounts of calcium and phosphate in parenteral nutrition (PN) solution for neonates is important for bone mass accretion. Because of the risk of calcium phosphate precipitation, a well‐documented incompatibility for inorganic salts, the concentrations of these electrolytes in PN are generally limited to 5 mmol/L. The aim of this study was to assess the risk of precipitation of calcium phosphate when organic calcium and phosphate salts are used instead of inorganic salts. Methods: Precipitation curves were determined for inorganic and organic calcium and phosphate salts in a PN solution favorable to precipitation (low concentration of amino acids and glucose) using visual inspection and particle counts. Results: The use of organic phosphate salt was associated with a decreased risk of precipitation of calcium phosphate. No precipitation occurred up to a concentration of 50 mmol/L of calcium and phosphate. In contrast, organic calcium salt only slightly decreased the risk of precipitation. Conclusion: Up to 50 mmol/L of organic calcium and phosphate salts can be safely mixed in PN, even in unstable conditions, making it possible to follow the current European recommendations for requirements in neonates.     

CaxP and Ca/P in the parenteral feeding of preterm infants

Preterm infants requiring prolonged intravenous feeding frequently develop pathologic fractures and rickets. Infants who receive large amounts of calcium have fewer fractures. This observation led us to determine the maximal amounts of calcium and phosphate that can be added to parenteral nutrition solutions without the precipitation of calcium phosphate and to determine the optimal ratio of calcium to phosphate in these solutions. Clinical observations and in vitro experiments indicate that the product of calcium x phosphate (CaxP) in the dextrose-amino acid solution should not exceed 75 square millimolar (square millimole per square liter) to prevent calcium phosphate precipitation in barium-impregnated silicone rubber catheters and should not exceed 100 square millimolar in solutions administered through peripheral veins. Seven intake and output studies were performed in preterm infants to determine the ratio of calcium to phosphate (Ca/P) in the total parenteral nutrition solutions that minimized urinary losses. A Ca/P ratio of 5.0 minimized the sum of the calcium plus phosphate losses in the urine. However, experience with long-term total parenteral nutrition in preterm infants, awareness of the acute and life-threatening effects of body phosphate depletion, and an unmeasured endogenous enteric calcium secretion all suggest that a Ca/P ratio of approximately 3.0 provides a safer compromise between the acute and serious complications of phosphate deficiency and the chronic problems of fractures and rickets due to calcium deficiency.     

The growth of microorganisms in total parenteral nutrition admixtures

Total nutrient admixtures (TNAs) containing glucose, amino acids, and lipid emulsion in one container and amino acid/dextrose solutions [conventional total parenteral nutrition (TPN) formulations] were studied in a controlled laboratory experiment for their ability to support the growth of microorganisms. Both TNA and conventional TPN formulations for peripheral and central venous administration with standard additives were inoculated with microorganisms to provide 10(1)-10(2) colony-forming units/ml (CFU/ml) of Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. The admixtures were stored at room temperature and samples for quantitative microbiology were taken at time 0, 6, 12, 24, 48, 72, and 96 hr. K. pneumoniae, E. coli, and P. aeruginosa were able to proliferate in central TNAs, but the growth of these organisms was retarded in conventional TPN solutions. In the peripheral formulations, K. pneumoniae and E. coli proliferated in both the TNA and conventional TPN systems, whereas P. aeruginosa grew well only in the peripheral TNA. S. epidermidis was not able to grow in any admixtures tested; however, C. albicans grew well in all admixtures, but growth was slower in the conventional central TPN. In conclusion, peripheral and central TNAs supported the growth of microorganisms significantly better than conventional TPN solutions.     

Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model

A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate.     

Effect of phosphorus on endogenous calcium losses during total parenteral nutrition

Intravenous phosphorus can reduce urinary calcium losses in patients receiving total parenteral nutrition (TPN). We investigated the effect of intravenous P on urinary and fecal Ca loss in intravenously fed normal and thyroparathyroidectomized (TPTX) rats to assess the role of parathyroid hormone (PTH) and endogenous fecal Ca losses. Doubling the intravenous P load during TPN decreased urinary Ca losses by 54% (0.299 vs 0.137 mmol/d) in intact rats and by 43% (0.514 vs 0.294 mmol/d) in TPTX rats. Increased P load in normal rats had no effect on urinary cyclic AMP excretion, serum Ca, serum P, serum 1,25-dihydroxycholecalciferol, or endogenous fecal Ca losses. These observations suggest that the hypocalciuric effect of P during TPN is independent of PTH and is not caused by a repartitioning of obligatory Ca losses from the renal to the intestinal route.     

Structure and adsorption properties of commercial calcium phosphate adjuvant

Calcium phosphate adjuvant is a commercially available vaccine adjuvant that potentiates the immune response to antigens. Although its name suggests that it is Ca3(PO4)2, X-ray diffraction, FTIR spectroscopy, thermal analysis and the Ca/P molar ratio identify commercial calcium phosphate adjuvant as non-stoichiometric hydroxyapatite, Ca10-x (HPO4)x (PO4)6-x (OH)2-x, where x varies from 0 to 2. The surface charge is pH-dependent (point of zero charge = 5.5). Consequently, commercial calcium phosphate adjuvant exhibits a negative surface charge at physiological pH and electrostatically adsorbs positively charged antigens. The presence of hydroxyls allows calcium phosphate adjuvant to adsorb phosphorylated antigens by ligand exchange with surface hydroxyls.     

Phosphate balance and distribution during total parenteral nutrition: effect of calcium and phosphate additives

Hypophosphatemia is occasionally observed during total parenteral nutrition (TPN). The phenomenon was recognized since the introduction of TPN and was attributed to preexisting phosphate deficits and inadequate phosphate supplements. Because of the close relationship between phosphate and calcium metabolisms, we speculated that calcium additives may also influence phosphate balance and distribution during TPN. We tested this hypothesis in previously fasted animals receiving TPN with variable amounts of calcium and maintenance or no phosphate. Fasting resulted in considerable losses of phosphate in the urine. Refeeding (with TPN) after fasting produced hypophosphatemia but only in animals receiving calcium additives and no maintenance phosphate in the solution. Addition of moderate or large amounts of calcium decreased phosphate in the muscle in groups not receiving maintenance phosphate. There were no significant changes in bone phosphate. Increasing calcium intake was accompanied by significant and progressive reductions in urine phosphate in animals receiving maintenance phosphate, thus increasing net phosphate retention in those groups. In other respects, refeeding with TPN after fasting displayed features compatible with those of the phosphate depletion syndrome, including hypophosphatemia, hypophosphaturia, hypercalcemia, and hypercalciuria. The magnitude of change in these parameters seemed to be dependent upon the amount of calcium added and the availability of phosphate in the solution.     

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)