Calcium/Phosphate Solubility Curves for Premasol and Trophamine Pediatric Parenteral Nutrition Formulations

Abstract

OBJECTIVES Calcium and phosphate incompatibility in parenteral nutrition formulations remains a critical concern for patient safety. This study examined calcium phosphate solubility for 2-in-1 admixtures prepared using 2 commercially available pediatric amino acid solutions (Premasol, Baxter Healthcare Corp; or Trophamine, B. Braun Medical Inc), applying identical test methods, storage conditions, and acceptance criteria. METHODS Parenteral 2-in-1 admixtures included amino acid; dextrose; static concentrations of sodium, potassium, and magnesium, and varying concentrations of calcium (0–60 mEq/L), phosphate (15–50 mmol/L), and cysteine. Three replicate samples were stored for 48 hours at 40°C ± 2°C and then visually inspected for particulate matter, evaluated for subvisible particulate matter, when particulate matter was noted, microscopic examination was performed to confirm the presence of calcium phosphate crystals. Pass criteria were: all replicates free of visible particulate matter related to calcium phosphate crystals and particle counts below US Pharmacopeia <788> limits. RESULTS Premasol and Trophamine generated identical calcium phosphate curves for 2% amino acid formulations containing 20% dextrose with/without cysteine, and similar curves for the 1% or 3% amino acid formulations containing 10% or 20% dextrose with/without cysteine. Calcium phosphate particles were identified in failed samples by scanning electron microscopy/energy dispersive X-ray spectroscopy. Calcium phosphate solubility was higher in formulations containing cysteine 40 mg/g amino acid vs. cysteine 20 mg/g amino acid and in cysteine 20 mg/g amino acid vs. no cysteine. CONCLUSIONS Admixtures made with 1%, 2%, or 3% Premasol or Trophamine have essentially equivalent calcium phosphate solubility curves when tested with identical methods, storage conditions, and acceptance criteria.

High particle counts in neonatal parenteral nutrition solutions with added cysteine: Relationship to crystal formation and effect of filtration on cysteine content

“…The fact that the increased particle counts detected using LO are not found on filters using light or electron microscopy suggests that the increased number of particles seen with LO may be complexes formed from less stable bonds or attractive forces that do not lead to crystal formation and are, therefore, not a significant safety risk. If this is the case, it calls into question if LO is the best method to evaluate calcium and phosphorus compatibility as has been questioned in a recent study 37 …”

“…If this is the case, it calls into question if LO is the best method to evaluate calcium and phosphorus compatibility as has been questioned in a recent study. 37…”

Quality improvement project in a neonatal intensive care unit reduced the prevalence and duration of hypophosphatemia with significant and sustainable results

“…Initial practice changes starting in 2016 included daily optimization of calcium and phosphorus by RDs. This included (1) adjusting PN dose and ratio of calcium and phosphorus dosing in PN to meet estimated needs (Table 1) and utilizing cysteine HCl to allow higher calcium and phosphorus concentration 28,29 as needed, (2) use of a secondary IV for delivery of additional phosphorus when needs could not be met with existing PN limitations, (3) earlier introduction of human milk fortifier to expressed breast milk feedings, and (4) augmenting oral phosphorus supplementation when needed. All these modalities were previously available; however, the T A B L E 1 Recommended intake of parenteral calcium, phosphorus, and magnesium for infants without alterations in metabolism; Excerpt from "Optimizing phosphorus in neonatal patients-A multimodal evidence-based guideline".…”