3% Sodium Intravenous Infusion

By
David W. Newton, BS Pharm, PhD, FAPhA, Professor
Department of Biopharmaceutical Sciences
Bernard J. Dunn School of Pharmacy
Shenandoah University
1775 North Sector Court
Winchester, Virginia 22601
E-mail: dnewton@su.edu

Member of the Editorial Board of the
Science and Technology for the Hospital Pharmacist newsletter

A few years ago one of my former students, identified anonymously here as Dr. PH, emailed the following order for a patient in the hospital in which he was shift pharmacist-in-charge:

"The physician wanted exactly 500 mL of 3% sodium solution consisting of 1/3 as sodium chloride and 2/3 as sodium acetate."

Dr. PH personally attempted, prudently sought, and disappointingly received answers greater than 10% different for the composition of the 3% sodium infusion solution from two groups of similarly assertive and knowledgeable colleagues (Sound like the Democrats and Republicans?). He resorted to me to resolve the disagreement between the staff members because I had taught him basic compounding and parenteral therapy pharmaceutical calculations. In accordance with HIPAA, Dr. PH did not disclose the medical diagnosis or reason for the 3% Na infusion other than "serum electrolyte and pH imbalance." My initial reply on agreeing to provide the correct calculations included a warning that the solution would be dangerously hypertonic in a peripheral vein.

First, I prepared Table 1 to chemically describe the contents of the 3% sodium (Na) infusion. Next, I performed calculations to determine the correct amounts of sodium chloride (NaCl) and sodium acetate (CH₃COON_a) in a 1/3 to 2/3 ratio to provide 15 g of Na in 500 mL. Finally, I determined volumes of commercially available injections that could be used. For example, the strength and volume of NaCl injection must provide 5 g of Na in the final 500 mL of 3% Na infusion because 5 g in 500 mL is equivalent to 1 g in 100 mL or 1%, and 1% is 1/3 of 3% (these simple proportions are the foundation for the more complex calculations that follow).

A.   The Sodium Chloride Injection Portion.

1. As delineated above, enough NaCl is needed to provide 5 g Na in 500 mL, which is 1% Na strength from NaCl or 1/3 of the total 3% Na as NaCl.
   
   
   1. X represents the correct amount of NaCl for 5 g Na or 1% Na strength in 500 mL.
   2. 5 g Na/X = 22.99 g Na/58.44 g NaCl, where 22.99 g and 58.44 g are atomic and molecular weights.
   3. X = 12.71 g NaCl in 500 mL for 1% Na strength.


2. The strength of NaCl injection must be adequate to provide 1% final Na strength in 500 mL when NaCl injection is ≤ 1/3 of 500 mL. Options; thus, include the following, where X represents the correct volume:
   
   
   1. 14.6% or 2.4 mEq/mL NaCl injection:
      12.71 g NaCl/X = 14.6 g NaCl/100 mL, X = 87.1 mL
   2. 23.4% or 4 mEq/mL NaCl injection:
      12.71 g NaCl/X = 23.4 g NaCl/100 mL, X = 54.3 mL

B.   The Sodium Acetate Injection Portion.

The USP monograph for sodium acetate injection specifies the content as CH₃COONa, but the monograph for sodium acetate allows either the anhydrous or trihydrate salt.¹

1. Enough CH₃COONa is needed to provide for 10 g Na in 500 mL, which is 2% Na strength from CH₃COONa or 2/3 of the total 3% Na as CH₃COONa.
   
   
1. X represents the correct amount of CH₃COONa for 10 g Na or 2% Na strength in 500 mL.
2. 10 g Na/X = 22.99 g Na/82.03 g CH₃COONa, where 22.99 g and 82.03 g are atomic and molecular weights.
3. X = 35.68 g CH₃COONa in 500 mL for 2% Na strength.
   
   
2. The strength of CH₃COONa injection must be adequate to provide 2% final Na strength in 500 mL when CH₃COONa injection is ≤ 2/3 of 500 mL. The only available option is 16.4% or 2 mEq/mL strength injection, where X represents the correct volume.
   
   
   1. 35.68 g CH₃COONa/X = 16.4 g CH₃COONa/100 mL.
   2. X = 217.6 mL.

C.   The Final 3% Na Infusion Solution.

1. Compounding summary.
   
   In an empty, sterile, non-pyrogenic infusion bag or bottle aseptically mix either 87.1 mL of 14.6% or 54.3 mL of 23.4% NaCl injection and 217.6 mL of 16.4% CH₃COONa injection. In both cases, the combined volume of the sodium salts injections is less than 500 mL; thus, the 500-mL final volume is achieved with sterile water for injection.
   
   
2. Theoretical osmolarity, mOsmol/L.
   
   
   1. From NaCl.

      mOsmola	2 mmol ionsb	1000 mmol	molc	12.71 gd	1000 mL	=	870 mOsmole
      mmola	mmol&nbps;saltb	mol	58.44 gc	500 mLd	L		Le
      aBy definition, 1 milliosmol, mOsmol, of osmotic pressure results from 1 millimole, mmol, of dissolved ions and molecules of any size and charge. bTheoretically, each molecule (ion pair) of NaCl fully dissociates into its Na+ and Cl- ions. cFormula or mol weight of NaCl. dAmount of NaCl in all 500 mL of 3% Na infusion solution. eThis is very hypertonic compared to isotonic human blood plasma at 300 mOsmol/L.

   2. From CH₃COONa.

      mOsmola	2 mmol ionsb	1000 mmol	molc	35.68 gd	1000 mL	=	1740 mOsmole
      mmola	mmol&nbps;saltb	mol	82.03 gc	500 mLd	L		Le
      aBy definition, 1 milliosmol, mOsmol, of osmotic pressure results from 1 millimole, mmol, of dissolved ions and molecules of any size and charge. bTheoretically each molecule (ion pair) of CH3COONa fully dissociates into its Na+ and CH3COO- ions. cFormula or mol weight of CH3COONa. dAmount of CH3COONa in all 500 mL of 3% Na infusion solution. eThis is very hypertonic compared to isotonic human blood plasma at 300 mOsmol/L.

   3. Total osmolarity: (870+1740) = 2610 mOsmol, which is more hypertonic than most central vein total parenteral nutrition formulations with 25% to 35% dextrose, 4% to 6% amino acids, and multiple electrolytes.
      
      
   4. Na concentration, mEq/mL.
      ([15 g Na/500 mL]x[mEq Na/0.02299 g Na]) = 1.3 mEq Na/mL.

Table 1. Formula Weights of Sodium, Sodium Chloride, and Sodium Acetate.

Reference

1. United States Pharmacopeial Convention, Inc. United States Pharmacopeia 36 ( Revision)-National Formulary 31. Rockville, MD: US Pharmacopeial Convention, Inc.; Official December 1, 2013 through April 30, 2014.

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