Phosphate Compatibility Research Articles

Use of sodium glycerophosphate in neonatal parenteral nutrition solutions to increase calcium and phosphate compatibility for preterm infants

Preterm infants require higher calcium and phosphate intake than term infants to facilitate adequate bone growth, but this is rarely met in parenteral nutrition (PN) solution because of the limited solubility of calcium and phosphate. This study aimed to evaluate the solubility of organic phosphate with calcium gluconate in neonatal PN solutions, simulating its clinical use. PN solutions were composed of calcium gluconate at 50 mEq/L and sodium glycerophosphate (NaGP) at 25mmol/L. Another component included 1% or 4% amino acid and 10% or 20% dextrose. For comparison, PN solution composed of potassium phosphate was also evaluated. Each solution was evaluated using the following methods: visual inspection, light obscuration particle count test, and pH measurement. To simulate the clinical condition, the solution was tested after compounding, after being stored at 25°C for 24h, and after being stored at 2°C-8°C for 2 or 9 days and subsequently at 25°C for 24h. There was no visual deposition in PN solution using NaGP in any of the concentrations and under any stored condition. The solution fulfilled the criteria of physical compatibility as < 25 particles/mL measuring ≥10μm in diameter and <3 particles/mL measuring ≥25μm in diameter. On the contrary, visual deposition was evidently noted in PN solution using potassium phosphate after its formulation, and the particle count significantly exceeded the range of physical compatibility. NaGP and calcium gluconate have significantly good compatibility in PN solution. The use of NaGP in neonatal PN prevents calcium and phosphorus precipitation, hence increasing their supply to preterm infants in meeting their growth requirement.

Precipitation of Heparin Products With Calcium Gluconate: The Activity of Inactive Ingredients.

Precipitation of Heparin Products With Calcium Gluconate: The Activity of Inactive Ingredients.

Experience of compounding total parenteral nutrition admixtures for preterm infants in a hospital pharmacy: evidence of calcium and phosphate compatibility problem

ObjectiveParenterally fed preterm newborn infants require large amounts of calcium and phosphate in a low volume of solution. The lower the volume of solution, the higher is the possibility of...

A.S.P.E.N. Clinical Guidelines

Parenteral nutrition (PN) is a high-alert medication available for patient care within a complex clinical process. Beyond application of best practice recommendations to guide safe use and optimize clinical outcome, several issues are better addressed through evidence-based policies, procedures, and practices. This document provides evidence-based guidance for clinical practices involving PN prescribing, order review, and preparation. A systematic review of the best available evidence was used by an expert work group to answer a series of questions about PN prescribing, order review, compounding, labeling, and dispensing. Concepts from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) format were applied as appropriate. The specific clinical guideline recommendations were developed using consensus prior to review and approval by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. The following questions were addressed: (1) Does education of prescribers improve PN ordering? (2) What is the maximum safe osmolarity of PN admixtures intended for peripheral vein administration? (3) What are the appropriate calcium intake and calcium-phosphate ratios in PN for optimal neonatal bone mineralization? (4) What are the clinical advantages or disadvantages of commercially available premade ("premixed") multichambered PN formulations compared with traditional/customized PN formulations? (5) What are the clinical (infection, catheter occlusion) advantages or disadvantages of 2-in-1 compared with 3-in-1 PN admixtures? (6) What macronutrient dosing limits are expected to provide for the most stable 3-in-1 admixtures? (7) What are the most appropriate recommendations for optimizing calcium (gluconate) and (Na- or K-) phosphate compatibility in PN admixtures? (8) What micronutrient contamination is present in parenteral stock solutions currently used to compound PN admixtures? (9) Is it safe to use the PN admixture as a vehicle for non-nutrient medication delivery? (10) Should heparin be included in the PN admixture to reduce the risk of central vein thrombosis? (11) What methods of repackaging intravenous fat emulsion (IVFE) into smaller patient-specific volumes are safe? (12) What beyond-use date should be used for (a) IVFE dispensed for separate infusion in the original container and (b) repackaged IVFE?

Probability‐Based Compatibility Curves for Calcium and Phosphates in Parenteral Nutrition Formulations

The information content of the calcium phosphate compatibility curves for adult parenteral nutrition (PN) solutions may benefit from a more sophisticated statistical treatment. Binary logistic regression analyses were evaluated as part of an alternate method for generating formulation compatibility curves. A commercial PN solution was challenged with a systematic array of calcium and phosphate concentrations. These formulations were then characterized for particulates by visual inspection, light obscuration, and filtration followed by optical microscopy. Logistic regression analyses of the data were compared with traditional treatments for generating compatibility curves. Assay-dependent differences were observed in the compatibility curves and associated probability contours; the microscopic method of precipitate detection generated the most robust results. Calcium and phosphate compatibility data generated from small-volume glass containers reasonably predicted the observed compatibility of clinically relevant flexible containers. The published methods for creating calcium and phosphate compatibility curves via connecting the highest passing or lowest failing calcium concentrations should be augmented or replaced by probability contours of the entire experimental design to determine zones of formulation incompatibilities. We recommend researchers evaluate their data with logistic regression analysis to help build a more comprehensive probabilistic database of compatibility information.

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

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. 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 x 2 x 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 mum at 7 time intervals over 48 hours stored at 30 degrees C +/- 0.2 degrees 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. 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 mum (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. 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.

Improving Pediatric Outcomes through Intravenous and Oral Medication Standardization

Standardization is an invaluable tool to promote safety, improve care, and decrease costs, which ultimately improves outcomes. However, a pediatric setting presents unique challenges with its wide variety of weights, medications, and needs that are distinctly different. Our goal was to develop and implement standards in complex high risk areas that show improved outcomes and safety. A computerized prescriber order entry program with decision support for pediatrics was developed for parenteral nutrition prescribing. The program included dosing, calculations, calcium phosphate compatibility checks, automated IV compounder interface, osmolarity route calculation, end product testing verification, aluminum exposure and many other quality improvements. This same electronic order program, interface to sterile compounders, and end product testing was used to standardize and make common non-manufactured intravenous solutions. The drip compounding process was reengineered to include standard concentrations, label changes, and beta-testing of a smart syringe pump with dosing ranges for pediatrics. Common standard oral doses were developed along with standard oral formulations. Total parenteral nutrition (TPN) error rates decreased from 7% to less than 1% and compatibility issues decreased from 36 to 1 per year. Neonatal osteopenia rates decreased from 15% to 2%. Results from end product testing of TPN solutions were within USP standards showing statistical correlation (p<0.001). Intravenous standardization decreased error rates by 15% and compounding time decreased by 12 minutes (64%). Drip standardization allowed for drug concentration and smart pump standardization and decreased drip errors by 73% from 3.1 to 0.8 per 1000 doses. Compounding errors decreased from 0.66 to 0.16 per 1000 doses and ten-fold errors decreased from 0.41 to 0.08 per 1000 doses. Eleven oral liquids, including 329 different doses, were standardized, decreasing the number of doses to 59 (83% change). This decreased workload 15%, wastage 90%, improved turnaround time 32%, and saved $15,000/year. One hundred evidence-based standard oral formulations were developed and used in 22 different hospitals.

Calcium and phosphate compatibility: Revisited again

The subject of the compatibility between calcium and phosphates was revisited in an April 1994 FDA safety alert,[1][1],[2][2] 6–16 years after the four seminal research articles appeared in 1978,[3][3] 1980,[4][4] 1982,[5][5] and 1988.[6][6] In the 1980s there were two case reports of nonfatal

Book Review: Trissel's Calcium and Phosphate Compatibility in Parenteral Nutrition

Book Review: Trissel's Calcium and Phosphate Compatibility in Parenteral Nutrition

Trisselʼs Calcium and Phosphate Compatibility in Parenteral Nutrition

Trisselʼs Calcium and Phosphate Compatibility in Parenteral Nutrition

Trisselʼs Calcium and Phosphate Compatibility in Parenteral Nutrition

Trisselʼs Calcium and Phosphate Compatibility in Parenteral Nutrition

Calcium and Phosphate Compatibility in Parenteral Nutrition

Nutrition in Clinical PracticeVolume 16, Issue 6 p. 372-372 Article Calcium and Phosphate Compatibility in Parenteral Nutrition Charles W. Jastram, Charles W. Jastram New Orleans, LASearch for more papers by this author Charles W. Jastram, Charles W. Jastram New Orleans, LASearch for more papers by this author First published: 01 December 2001 https://doi.org/10.1177/088453360101600616AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume16, Issue6December 2001Pages 372-372 RelatedInformation

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.

Influence of elevated temperature on calcium and phosphate compatibility in admixtures

Influence of elevated temperature on calcium and phosphate compatibility in admixtures