Journal of Parenteral and Enteral Nutrition http://pen.sagepub.com/
Physical Compatibility of Sodium Glycerophosphate and Calcium Gluconate in Pediatric Parenteral Nutrition Solutions Mark MacKay and Collin Anderson JPEN J Parenter Enteral Nutr published online 2 April 2014 DOI: 10.1177/0148607114528982 The online version of this article can be found at: http://pen.sagepub.com/content/early/2014/03/31/0148607114528982
Published by: http://www.sagepublications.com
On behalf of:
The American Society for Parenteral & Enteral Nutrition
Additional services and information for Journal of Parenteral and Enteral Nutrition can be found at: Email Alerts: http://pen.sagepub.com/cgi/alerts Subscriptions: http://pen.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Apr 2, 2014 What is This?
Downloaded from pen.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 6, 2014
528982
research-article2014
PENXXX10.1177/0148607114528982Journal of Parenteral and Enteral NutritionMacKay and Anderson
Brief Communication
Physical Compatibility of Sodium Glycerophosphate and Calcium Gluconate in Pediatric Parenteral Nutrition Solutions
Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 201X 1–4 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607114528982 jpen.sagepub.com hosted at online.sagepub.com
Mark MacKay, BS Pharm1; and Collin Anderson, PharmD, PhD1
Abstract Background: The solubility of inorganic calcium and phosphate in parenteral solutions can be complicated in pediatrics due to the dosing of calcium and phosphorus at the saturation point. The purpose of this study was to test the solubility of sodium glycerophosphate (NaGP) with calcium gluconate in pediatric parenteral nutrition (PN) solutions. Methods: Five PN solutions were compounded by adding calcium gluconate at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L. Each of the 5 solutions was compounded using 1.5% and 4% amino acids, cysteines, and lipids. Compatibility was evaluated by visual inspection (precipitation, haze, and color change). Solutions were evaluated microscopically for any microcrystals and measured by a turbidimeter for changes in turbidity. Solutions were further analyzed using United States Pharmacopeia 788 standards. Six hundred seventy-one PN solutions were compounded at various concentrations and evaluated for visual stability. Results: Compatibility testing showed no changes in the PN solution in any of the concentrations tested. Microscopically, no microcrystals were detected. The turbidimeter measurements had changes of ≤0.14 nephelometric turbidity units for all test solutions. There were no visual changes in any of the 671 PN solutions. Conclusion: It is recommended that NaGP replace sodium phosphate in PN solutions. This would eliminate the concern of calcium and phosphorus precipitation and the need of any saturation curves. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)
Keywords sodium glycerophosphate; parenteral nutrition; compatibility
Clinical Relevancy Statement Parenteral nutrition (PN) is considered a high-risk medication. One of the risks of compounding PN is the interaction of inorganic calcium and phosphorus forming crystals within the parenteral solution. Saturation curves have been developed to prevent precipitation. Organic sodium glycerophosphate is not susceptible to the same compatibility problems as inorganic phosphorus. The clinical relevance of this study supports practitioners providing enough calcium and phosphorus to meet the needs of more neonatal patients without fear of administering unstable parenteral solutions.
Background Equations, ratios, graphs, and guidance statements have been developed to assist practitioners in preventing calcium and phosphorus precipitates in parenteral solutions.1-5 Due to a national shortage of sodium phosphate, the Food and Drug Administration (FDA) recently exercised regulatory discretion, allowing for the temporary importation of organic sodium glycerophosphate (NaGP) from Norway6 (Table 1). The package insert indicates that “at higher concentrations, solutions of calcium and phosphorus may exist together without precipitating
into insoluble salt complex.”7 Per the manufacturer, solutions containing up to 120 mmol/L of NaGP and 96 mEq/L of calcium (as calcium chloride) are compatible.8 The purpose of this study was to test the solubility of NaGP with calcium gluconate in pediatric parenteral nutrition (PN) solutions at various concentrations.
Methods Five PN solutions, each with a final volume of 200 mL, based on a 2-kg patient at 100 mL/kg/d, were compounded by adding calcium gluconate at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L with a dextrose concentration of 15% and standard dose based From the 1Primary Children’s Hospital, Salt Lake City, Utah. Financial disclosure: None declared. Received for publication December 23, 2013; accepted for publication February 25, 2014. Corresponding Author: Mark MacKay, BS Pharm, Primary Children’s Hospital, 100 North Mario Capecchi Drive, Salt Lake City, UT 84113, USA. Email: [email protected].
Downloaded from pen.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 6, 2014
2
Journal of Parenteral and Enteral Nutrition XX(X)
Table 1. Sodium Glycerophosphate Product Information. Chemical Name
Phosphate Sodium Type of Concentration Concentration Phosphate pH
Sodium 1 mmol/mL glycerophosphate
2 mEq/mL
Organic
7.4
Table 2. Standard Amounts of Electrolytes and Vitamins in Parenteral Nutrition Solutions. Ion Sodium Potassium Chloride Acetate Magnesium Vitamin MVI Pediatric
Unit mEq/kg/d mEq/kg/d mEq/kg/d mEq/kg/d mEq/kg/d Unit mL/kg
Usual Daily Requirement Patient Dose 2–4 2–3 2–4 2–4 0.3–0.5
4.0 3.0 2.99 2.25 0.3
Usual Daily Requirement Patient Dose 2; maximum 5
4
MVI Pediatric from Baxter (Round Lake, IL).
on weight for vitamins and minerals (Table 2). All products used in this study were FDA approved for use in the United States. Each of the 5 PN solutions was tested for compatibility using variable concentrations of TrophAmine (B Braun Medical Inc, Irvine, CA), cysteine (American Regent Laboratories, Shirley, NY), and Intralipid (Fresenius Kabi, Runcorn, UK). In each of the 5 PN solutions, TrophAmine was tested at 1.5% and 4% amino acid concentrations. Forty mg of cysteine was added for every gram of amino acid in the 1.5% and 4% amino acid solutions as a separate test in the 5 PN solutions. Intralipid (lipid) was tested separately at 3 g/kg/d in a concentration of amino acids of 1.5% and 4%. In order to test the stability of NaGP and calcium gluconate in a PN solution containing lipids, the pH of each PN solution including lipids was determined. PN solutions were subsequently remade without lipids and buffered with sodium hydroxide (1 N) to the corresponding pH. This allowed for visual inspection as if the lipids were added. The pH of each PN test was measured using a Hanna pH meter (Hanna Instruments, Smithfield, RI). Each of the 5 PN solutions was divided into 20-mL aliquots and tested in triplicate, for a total of 90 tests. Compatibility of each aliquot was tested at room temperature and 37°C using a water bath over 24 hours. Solutions were placed in a water bath at 37°C for 24 hours to simulate pediatric conditions similar to radiant warmers, bilirubin lights, and body temperature. Visual inspection, evaluated against black and white backgrounds at the beginning and end of the room temperature and water bath testing, was used to detect particulate matter, precipitation, haze, and color change. Solutions were further inspected using a 2100Q turbidimeter (Hach Co, Loveland, CO) to determine the turbidity of each solution. Solutions were checked
Figure 1. Compatible concentrations of sodium glycerophosphate and calcium gluconate tested in 1.5% and 4% amino acids in parenteral nutrition solutions, cysteines, and lipids.
microscopically at 100× (Motic SMZ-168, Richmond, BC, Canada) for microcrystals. Solutions were further analyzed using a microscopic particle count test according to the United States Pharmacopeia standards, following adherence to both the preparation and analysis.9 Solutions are considered physically compatible if the crystal count is
Physical Compatibility of Sodium Glycerophosphate and Calcium Gluconate in Pediatric Parenteral Nutrition Solutions Mark MacKay and Collin Anderson JPEN J Parenter Enteral Nutr published online 2 April 2014 DOI: 10.1177/0148607114528982 The online version of this article can be found at: http://pen.sagepub.com/content/early/2014/03/31/0148607114528982
Published by: http://www.sagepublications.com
On behalf of:
The American Society for Parenteral & Enteral Nutrition
Additional services and information for Journal of Parenteral and Enteral Nutrition can be found at: Email Alerts: http://pen.sagepub.com/cgi/alerts Subscriptions: http://pen.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Apr 2, 2014 What is This?
Downloaded from pen.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 6, 2014
528982
research-article2014
PENXXX10.1177/0148607114528982Journal of Parenteral and Enteral NutritionMacKay and Anderson
Brief Communication
Physical Compatibility of Sodium Glycerophosphate and Calcium Gluconate in Pediatric Parenteral Nutrition Solutions
Journal of Parenteral and Enteral Nutrition Volume XX Number X Month 201X 1–4 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607114528982 jpen.sagepub.com hosted at online.sagepub.com
Mark MacKay, BS Pharm1; and Collin Anderson, PharmD, PhD1
Abstract Background: The solubility of inorganic calcium and phosphate in parenteral solutions can be complicated in pediatrics due to the dosing of calcium and phosphorus at the saturation point. The purpose of this study was to test the solubility of sodium glycerophosphate (NaGP) with calcium gluconate in pediatric parenteral nutrition (PN) solutions. Methods: Five PN solutions were compounded by adding calcium gluconate at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L. Each of the 5 solutions was compounded using 1.5% and 4% amino acids, cysteines, and lipids. Compatibility was evaluated by visual inspection (precipitation, haze, and color change). Solutions were evaluated microscopically for any microcrystals and measured by a turbidimeter for changes in turbidity. Solutions were further analyzed using United States Pharmacopeia 788 standards. Six hundred seventy-one PN solutions were compounded at various concentrations and evaluated for visual stability. Results: Compatibility testing showed no changes in the PN solution in any of the concentrations tested. Microscopically, no microcrystals were detected. The turbidimeter measurements had changes of ≤0.14 nephelometric turbidity units for all test solutions. There were no visual changes in any of the 671 PN solutions. Conclusion: It is recommended that NaGP replace sodium phosphate in PN solutions. This would eliminate the concern of calcium and phosphorus precipitation and the need of any saturation curves. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx)
Keywords sodium glycerophosphate; parenteral nutrition; compatibility
Clinical Relevancy Statement Parenteral nutrition (PN) is considered a high-risk medication. One of the risks of compounding PN is the interaction of inorganic calcium and phosphorus forming crystals within the parenteral solution. Saturation curves have been developed to prevent precipitation. Organic sodium glycerophosphate is not susceptible to the same compatibility problems as inorganic phosphorus. The clinical relevance of this study supports practitioners providing enough calcium and phosphorus to meet the needs of more neonatal patients without fear of administering unstable parenteral solutions.
Background Equations, ratios, graphs, and guidance statements have been developed to assist practitioners in preventing calcium and phosphorus precipitates in parenteral solutions.1-5 Due to a national shortage of sodium phosphate, the Food and Drug Administration (FDA) recently exercised regulatory discretion, allowing for the temporary importation of organic sodium glycerophosphate (NaGP) from Norway6 (Table 1). The package insert indicates that “at higher concentrations, solutions of calcium and phosphorus may exist together without precipitating
into insoluble salt complex.”7 Per the manufacturer, solutions containing up to 120 mmol/L of NaGP and 96 mEq/L of calcium (as calcium chloride) are compatible.8 The purpose of this study was to test the solubility of NaGP with calcium gluconate in pediatric parenteral nutrition (PN) solutions at various concentrations.
Methods Five PN solutions, each with a final volume of 200 mL, based on a 2-kg patient at 100 mL/kg/d, were compounded by adding calcium gluconate at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L with a dextrose concentration of 15% and standard dose based From the 1Primary Children’s Hospital, Salt Lake City, Utah. Financial disclosure: None declared. Received for publication December 23, 2013; accepted for publication February 25, 2014. Corresponding Author: Mark MacKay, BS Pharm, Primary Children’s Hospital, 100 North Mario Capecchi Drive, Salt Lake City, UT 84113, USA. Email: [email protected].
Downloaded from pen.sagepub.com at UNIV OF SOUTHERN CALIFORNIA on April 6, 2014
2
Journal of Parenteral and Enteral Nutrition XX(X)
Table 1. Sodium Glycerophosphate Product Information. Chemical Name
Phosphate Sodium Type of Concentration Concentration Phosphate pH
Sodium 1 mmol/mL glycerophosphate
2 mEq/mL
Organic
7.4
Table 2. Standard Amounts of Electrolytes and Vitamins in Parenteral Nutrition Solutions. Ion Sodium Potassium Chloride Acetate Magnesium Vitamin MVI Pediatric
Unit mEq/kg/d mEq/kg/d mEq/kg/d mEq/kg/d mEq/kg/d Unit mL/kg
Usual Daily Requirement Patient Dose 2–4 2–3 2–4 2–4 0.3–0.5
4.0 3.0 2.99 2.25 0.3
Usual Daily Requirement Patient Dose 2; maximum 5
4
MVI Pediatric from Baxter (Round Lake, IL).
on weight for vitamins and minerals (Table 2). All products used in this study were FDA approved for use in the United States. Each of the 5 PN solutions was tested for compatibility using variable concentrations of TrophAmine (B Braun Medical Inc, Irvine, CA), cysteine (American Regent Laboratories, Shirley, NY), and Intralipid (Fresenius Kabi, Runcorn, UK). In each of the 5 PN solutions, TrophAmine was tested at 1.5% and 4% amino acid concentrations. Forty mg of cysteine was added for every gram of amino acid in the 1.5% and 4% amino acid solutions as a separate test in the 5 PN solutions. Intralipid (lipid) was tested separately at 3 g/kg/d in a concentration of amino acids of 1.5% and 4%. In order to test the stability of NaGP and calcium gluconate in a PN solution containing lipids, the pH of each PN solution including lipids was determined. PN solutions were subsequently remade without lipids and buffered with sodium hydroxide (1 N) to the corresponding pH. This allowed for visual inspection as if the lipids were added. The pH of each PN test was measured using a Hanna pH meter (Hanna Instruments, Smithfield, RI). Each of the 5 PN solutions was divided into 20-mL aliquots and tested in triplicate, for a total of 90 tests. Compatibility of each aliquot was tested at room temperature and 37°C using a water bath over 24 hours. Solutions were placed in a water bath at 37°C for 24 hours to simulate pediatric conditions similar to radiant warmers, bilirubin lights, and body temperature. Visual inspection, evaluated against black and white backgrounds at the beginning and end of the room temperature and water bath testing, was used to detect particulate matter, precipitation, haze, and color change. Solutions were further inspected using a 2100Q turbidimeter (Hach Co, Loveland, CO) to determine the turbidity of each solution. Solutions were checked
Figure 1. Compatible concentrations of sodium glycerophosphate and calcium gluconate tested in 1.5% and 4% amino acids in parenteral nutrition solutions, cysteines, and lipids.
microscopically at 100× (Motic SMZ-168, Richmond, BC, Canada) for microcrystals. Solutions were further analyzed using a microscopic particle count test according to the United States Pharmacopeia standards, following adherence to both the preparation and analysis.9 Solutions are considered physically compatible if the crystal count is
