Possible Incompatibility between Amino Acids and Copper in Solutions for Pediatric Parenteral Nutrition.

The nutrient formulas used for parenteral nutrition are highly complex admixtures of multiple solutions, infused by the IV route to patients who are unable to receive nutrition by mouth or by the enteral route. The administered products contain macronutrients (amino acids, dextrose, and lipids), electrolytes (sodium, potassium, calcium, phosphate, magnesium, chloride, and acetate), micronutrients (vitamins, trace elements), and water. The solution for parenteral administration can be prepared as a “2-in-1” solution, with lipids being infused separately from the other components, or as a “3-in-1” admixture, in which all components are mixed together. The complexity of these solutions poses a significant risk of incompatibility between components. The most widely known incompatibility involving components of parenteral nutrition solutions is precipitation of calcium phosphate. In 1994, the US Food and Drug Administration published a safety communication describing cases of incompatibility between calcium and phosphate in parenteral nutrition solutions, in which infusion of the solutions resulted in death (2 patients) or respiratory distress (2 patients). Measures taken to prevent adverse events related to incompatibilities include the use of filters during infusion, specifically 0.22-μm filters for 2-in-1 solutions and 1.2-μm filters for 3-in-1 admixtures. For compounded parenteral nutrition solutions, components should be added in the same order every time, and contact between incompatible solutions should be minimized. Specifically, phosphates should be added at the beginning of the mixing sequence, and calcium gluconate should be added last, such that the calcium is added when the volume of the solution being compounded is at its maximum. The solubility of calcium phosphate should be evaluated for all parenteral nutrition orders, using validated solubility curves specific to the brand of amino acids used. Pharmacists preparing and validating parenteral nutrition orders should always inspect bags for visually detectable precipitates before releasing them for infusion. Unfortunately, the measures described above do not always prevent incompatibilities in parenteral nutrition solutions. This report describes visual observation of precipitates in 3 different parenteral nutrition solutions.