Solubility Study of Zinc and Phosphates in PN and IV Fluid. Rex Speerhas, RPh, BCNSP Nutrition Support Clinical Specialist

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Solubility Study of Zinc and Phosphates in PN and IV Fluid Rex Speerhas, RPh, BCNSP Nutrition Support Clinical Specialist

What is that Brown Precipitate?

What is that Brown Precipitate?

Background Home Parenteral Nutrition (HPN) consumers admitted for sepsis Blood cultures and urine cultures

What is that Brown Precipitate? PN switched to Dextrose 5% + PN ingredients until blood cultures are negative Insulin removed Calcium gluconate removed Infused over 24 hours

What is that Brown Precipitate? Brown precipitate seen on filter in several IVs No record of any history of precipitate in HPN fluids

What is that Brown Precipitate? Filter with precipitate sent for analysis via electron microscope What is your guess as to what it was?

What is that Brown Precipitate? Dextrose 5% 1000 ml Magnesium sulfate 36 meq Sodium phosphates 24 mmol Potassium chloride 40 meq Sodium acetate 55 meq MVI Adult 10 ml Multitrace-4 Conc. 1 ml Copper 0.8 mg Selenium 120 mcg Zinc 10 mg Famotidine 40 mg Octreotide 600 mcg

What is that Brown Precipitate? ZINC PHOSPHATE Like calcium, which precipitates more readily with phosphates in IV fluids, zinc does as well. As divalent cations, both have limited solubility with phosphates

What is that Brown Precipitate? The conventional synthesis method of zinc phosphate consists in its preparation from an aqueous solution using zinc sulfate and sodium dihydrogen phosphate according to the following reaction: 3ZnSO4 7H2O + 2Na2HPO4 2H2O Zn3(PO4)2 4H2O + H2SO4 + 2Na2SO4 + 21H2O

What is that Brown Precipitate? Zinc phosphate has a solubility product (Ksp) of 9.0 x 10-33

Solubility Study of Zinc and Phosphates in PN and IV Fluid Hypothesis: By changing the concentrations of zinc and phosphates, we can find the maximum amounts that may be added together to avoid precipitation. Aim: This study will help decide the maximum levels of zinc (as chloride or sulfate) and phosphates that can be admixed in both parenteral nutrition (PN) and IV fluids with electrolytes

Solubility Study of Zinc and Phosphates in PN and IV Fluid Zinc (15 mg) and sodium phosphates (24 mmol) were admixed in a solution of 5% dextrose with electrolytes and resulted in a precipitation in the filter. When repeated, the precipitate reoccurred. When the same solution was admixed without zinc, the precipitate did not occur. When the same solution was admixed without phosphates, the precipitate did not occur. No precipitate appeared in a PN formula with same ingredients.

Zinc phosphate solubility Original IV Formula: 1000 ml Dextrose 5% 50 g Magnesium sulfate 36 meq Sodium phosphates 24 mmol Potassium chloride 40 meq Sodium acetate 55 meq MVI Adult 10 ml (contains riboflavin phosphate) Multitrace-4 Conc. 1 ml Copper 0.8 mg Selenium 120 mcg Zinc 10 mg Famotidine 40 mg Octreotide 600 mcg

Zinc phosphate solubility D5lytes with 15 mg zinc and 12 mmol phosphorus (as sodium phosphates) 6 mmol phosphorus (as sodium phosphates) Continue down in 3 mmol increments until precipitate disappears. Then increase by 1 mmol until precipitate appears.

Zinc phosphate solubility D5lytes with 24 mmol phosphorus and 10 mg zinc 5 mg zinc Continue down in 2 mg increments until precipitate disappears. Then increase by 1 mg until precipitate appears.

Zinc phosphate solubility HPN with 15 mg zinc and 27 mmol phosphorus (as sodium phosphates) 30 mmol phosphorus (as sodium phosphates) Continue up in 3 mmol increments until precipitate disappears. Then decrease by 1 mmol until precipitate appears

Zinc phosphate solubility HPN with 24 mmol phosphorus and 17 mg zinc 19 mg zinc Continue up in 2 mg increments until precipitate disappears. Then decrease by 1 mg until precipitate appears.

Zinc (mg) Zinc phosphate solubility in IV Fluid D5lytes: Zinc + Phosphates precipitation 25 20 15 Series1 10 5 0 0 5 10 15 20 25 30 Sodium phosphate (mmol)

Zinc (mg) Zinc phosphate solubility in PN PN: Zinc + Phosphates NO PRECIPITATION 60 50 40 30 Series1 20 10 0 0 50 100 150 200 250 Sodum phosphate (mmol)

Solubility Study of Zinc and Phosphates in PN and IV Fluid Results: All mixtures of zinc and phosphates tested in D5lytes precipitated. All mixtures of zinc and phosphates tested in PN did not precipitate. The tested ph of the IV fluid and the PN mixtures was similar.

Conclusion When switching from HPN to D5 + PN lytes: Remove insulin Remove calcium REMOVE ZINC

References Selected Solubility Products and Formation Constants at 25 C. Retrieved February 21st, 2011, from http://www.csudh.edu/oliver/chemdata/data-ksp.htm Solubility Product Constants, Ksp. Retrieved February 23rd, 2011, from http://www.chem.purdue.edu/gchelp/howtosolveit/equili brium/solubility_products.htm Allwood MC, Greenwood M. Assessment of trace element compatibility in total parenteral nutrition infusions. Pharm Weekbl [Sci]. 1992;14(5): 321-324. Quimby OT, McCune HW. Precipitation of zinc phosphates from solutions of sodium ortho-, pyro-, and triphosphate. Anal. Chem. 1957;29(2): 248-253.