Prefilter and Postfilter Cysteine/Cystine and Copper Concentrations in Pediatric Parenteral Nutrition Solutions

Abstract

Pediatric amino acid products contain lower concentrations of methionine and require the addition of L-cysteine HCl just before infusion. Reports of a potential interaction between cysteine and copper, a routine addition to parenteral nutrition solutions, have appeared in the literature. This study serially evaluated cysteine/cystine and copper concentrations pre- and postfilter (0.22 microns) in two parenteral nutrition formulations prescribed for normal fluid (NF) or fluid-restricted (FR) pediatric patients. Solutions were infused via a peristaltic pump in vitro for 24 hours. Pre- and postfilter samples were obtained immediately after the infusion began (time 0) and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours during the infusion. At 24 hours pre- and postfilter, cysteine/cystine were quantitated at 87.3% and 85% of the initial concentrations, respectively, for the NF solution and 92% and 91.5% for the FR solution. Pre- and postfilter copper was quantitated at 87.5% and 92.5% of the initial concentrations, respectively, for the NF solution and 88.2% and 95.2% for the FR solution. The 24 hour area under the curve for cysteine/cystine was 88.4% for the NF solution and 96.4% for the FR solution. For copper, the area under the curve for the NF solution was 99% and 96.7% for the FR solution. There was no visual evidence of incompatibility or precipitation. We conclude that copper-containing parenteral nutrition solutions with L-cysteine HCl added immediately before infusion are relatively stable after compounding and infusion over 24 hours.

Calcium Chloride and Calcium Gluconate in Neonatal Parenteral Nutrition Solutions with Added Cysteine: Compatibility Studies Using Laser Light Obscuration Methodology

“…One study in which cysteine was added at the time of compounding measured prefilter and postfilter concentrations of cysteine/cystine after 24 hours at room temperature and did not find a significant decrease in concentrations postfiltration, which were 85.0%-91.5% of the initial concentration. 16 A recent study of the same AA additive with the same amount of cysteine added at the time of compounding found that cysteine concentrations decreased 57.9%-63.5% after 24 hours at room temperature. 18 The decrease in cysteine concentrations was felt to be due to oxidation to cystine, which is less soluble.…”

“…It is unclear if the interaction between CaGlu and cysteine limits the availability of cysteine from neonatal PN solutions to the patient when cysteine is added at the time of compounding due to formation of particles that would be filtered out of solutions with the standard 0.22‐μm filter that is used when administering neonatal PN. One study in which cysteine was added at the time of compounding measured prefilter and postfilter concentrations of cysteine/cystine after 24 hours at room temperature and did not find a significant decrease in concentrations postfiltration, which were 85.0%–91.5% of the initial concentration . A recent study of the same AA additive with the same amount of cysteine added at the time of compounding found that cysteine concentrations decreased 57.9%–63.5% after 24 hours at room temperature .…”

“…A study of neonatal PN solutions where, compared with those studies, [13][14][15] higher amounts of cysteine were added at the time of compounding but a lower concentration (30-45 mcg/dL) of copper was used, did not find evidence of a significant interaction between copper and cysteine. 16 The PN solutions in the current study contained 20 mcg/dL of copper.…”

In Vitro Assessment of Interaction Between Amino Acids and Copper in Neonatal Parenteral Nutrition

“…Previous studies have indicated that certain trace elements (TEs) may interact with other nutrients, leading to precipitation formation 12 . ‐ 19 TEs could react with proteins through redox reactions to form high‐affinity complexes.…”

Review of Copper Provision in the Parenteral Nutrition of Adults

“…It may also be influenced by the timing of additions. When cysteine was added to PN immediately before infusion, no significant differences were observed between prefilter and postfilter concentrations of Cu and cysteine, nor was there visible precipitation 132 . The authors concluded that L‐cysteine added to PN immediately before infusion is stable over 24 hours of infusion.…”