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Effect of the Intravenous Lipid Emulsions on the Availability of Calcium when using Organic Phosphate in TPN Admixtures

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Abstract

Purpose

The addition of high amounts of calcium remains a pharmaceutical concern due to its precipitation with phosphate in total parenteral nutrient (TPN) admixtures, compromising also the stability of the lipid emulsion.

Materials and Methods

Calcium-phosphate solubility was compared when using binary PN solutions versus all-in-one TPN (admixtures with lipid emulsions) in three formulas using organic calcium gluconate and gulcose-1-phosphate.

Results

It was found that variation of Ca–P solubility exists between formulation with or without lipid emulsions. Concentrations of Ca decreased after filtrations of all admixtures (from 5% to 30%) and it was more significant in binary solutions. Precipitation has been observed by microscopy at high concentrations of both organic Ca–P after critical conditions of storage (24 h at 37°C plus one day at ambient temperature) for admixtures containing 1% amino acids and 8% glucose with or without lipids compared to admixtures containing 2% or 3.5% amino acids and 14% glucose.

Conclusions

These data demonstrated that availability of Ca using organic glucose-1-phosphate increased when lipids were present in TPN admixtures, without alteration of the lipid emulsion. Thus, high amounts of Ca (up to 30 mmol/l) and phosphates (up to 40 mmol/l) might be provided safely in parenteral nutrition admixtures.

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Abbreviations

CaGlu:

calcium gluconate

G1P:

glucose-1-phosphate

IV:

intravenous

IVLEs:

intravenous lipid emulsions

PN:

parenteral nutrition

TPN:

total parenteral nutrition

References

  1. P. W. Niemiec, and T. W. Vanderveen. Compatibility considerations in parenteral nutrient solutions. Am. J. Hosp. Pharm. 41:893–911 (1984).

    PubMed  CAS  Google Scholar 

  2. M. I. Barnett, A. G. Cosslett, J. R. Duffield, D. A. Evans, S. B. Hall, and D. R. Williams. Parenteral Nutrition: Pharmaceutical problems of compatibility and stability. Drug Safety. 5(1):101–106 (1990).

    Article  PubMed  CAS  Google Scholar 

  3. D. F. Driscoll, D. W. Newton, and B. R. Bistrian. Precipitation of calcium phosphate from parenteral nutrient fluids. Am. J. Hosp. Phar. 51:28–34 (1994).

    Google Scholar 

  4. M. C. Allwood, and M. C. J. Kearney. Compatibility and stability of additives in parenteral nutrition admixtures. Nutrition. 14(9):697–706 (1998).

    Article  PubMed  CAS  Google Scholar 

  5. J. B. Knowles, G. Cusson, M. Smith, and M. D. Sitrin. Pulmonary deposition of calcium phosphate crystals as a complication of home parenteral nutrition. JPEN. J. Parenter. Enteral Nutr. 13:209 (1989).

    Article  PubMed  CAS  Google Scholar 

  6. S. E. Hill, L. S. Heldman, E. D. H. Goo, and P. E. Whippo. Fatal microvascular pulmonary emboli from precipitation of total nutrient admixture solution. JPEN. J. Parenter. Enteral Nutr. 20:81–88 (1996).

    Article  PubMed  CAS  Google Scholar 

  7. Food and Drug Administration. Safety alert: hazards of precipitation associated with parenteral nutrition. Am. J. Hosp. Pharm. 51:1427–1428 (1994).

    Google Scholar 

  8. K. A. Fitzgerald, and M. W. MacKay. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing Aminosyn-PF. Am. J. Hosp. Pharm. 44:1396–1400 (1987).

    PubMed  CAS  Google Scholar 

  9. P. Raupp, R. V. Kries, H. G. Pfahl, and F. Manz. Glycero- vs glucose phosphate in parenteral nutrition of premature infants: a comparative in vitro evaluation of calcium phosphorus compatibility. JPEN. J. Parenter. Enteral Nutr. 15:469–473 (1991).

    Article  PubMed  CAS  Google Scholar 

  10. E. Levadoux, V. Sautou-Miranda, A. Arvouet, S. Corny-Peccoux, and J. Chopineau. Stabilité des mélanges binaires de nutrition parentérale pédiatriques, contenant calcium et phosphates. J. Pharm. Clin. 15:28–33 (1996).

    Google Scholar 

  11. L. Periera-da-Silva, A. V. Nurmamodo, J. M. Amaral, M. L. Rosa, M. C. Almeida, and M. L. Ribeiro. Compatibility of calcium and phosphate in four P.N. solutions for preterm neonates. Am. J. Health-Syst. Pharm. 60:1041–1044 (2003).

    Google Scholar 

  12. L. A. Robinson, and B. T. Wright. Central venous catheter occlusion caused by body-heat-mediated calcium phosphate precipitation. Am. J. Hosp. Pharm. 39:120–121 (1982).

    PubMed  CAS  Google Scholar 

  13. B. Dunham, S. Marcuard, P. G. Khazanie, G. Meade, T. Craft, and K. Nichols. The solubility of calcium and phosphorus in neonatal total parenteral nutrition solutions. JPEN. J. Parenter. Enteral Nutr. 15:608–611 (1991).

    Article  PubMed  CAS  Google Scholar 

  14. D. S. Chaieb, J. C. Chaumeil, S. Jebnoun, N. Khrouf, A. Hedhili, and S. Sfar. Calcium and phosphate compatibility and stability studies in different neonatal parenteral nutrition mixtures. EJHP-S. 12:35–40 (2006)Full text at: www.ejhp.org.

    Google Scholar 

  15. M. Prinzivalli, and S. Ceccarelli. Sodium d-fructose-1,6-diphosphate vs. Sodium mono-hydrogen phosphate in total parenteral nutrition: a comparative in vitro assessment of calcium phosphate compatibility. J. Parenter. Enter. Nutr. 23(6):326–332 (1999).

    Article  CAS  Google Scholar 

  16. W. Hicks, and G. Hardy. Fructose-1,6-diphosphate can improve long term stability of home parenteral nutrition (HPV) admixtures. Rivista Italiana di-Nutrizione ed Enterale. 19:144–151 (2001).

    Google Scholar 

  17. J. J. Maswoswe, A. U. Okpara, and M. A. Hilliard. An old nemesis: Calcium and phosphate interaction in TPN admixtures. Hosp. Pharm. 30(7):579–586 (1995).

    Google Scholar 

  18. D. F. Driscoll, J. Nehne, H. Peterss, K. Klutsch, B. R. Bistrian, and W. Niemann. Physicochemical stability of intravenous lipid emulsions as all-in-one admixtures intended for the very young. Clin. Nutr. 22(5):489–495 (2003).

    Article  PubMed  CAS  Google Scholar 

  19. J. C. Chaumeil, and D. Brossard. Stabilité des émulsions lipidiques utilisées en nutrition parentérale. Nutr. Clin. Metab. 7:55–64 (1993).

    Google Scholar 

  20. C. Washington, J. A. Ferguson, and S. E. Irwin. Computational prediction of the stability of lipid emulsions in total nutrient admixtures. J. Pharm. Sci. 82:808–812 (1993).

    Article  PubMed  CAS  Google Scholar 

  21. C. Washington. Stability of lipid emulsions for drug delivery. Adv. Drug Delivery Rev. 20:131–145 (1996).

    Article  CAS  Google Scholar 

  22. O. Corriol, S. Crauste-Manciet, P. Arnaud, F. Brion, D. Brossard, R. Causse, J. C. Chaumeil, R. Collomp, L. Cynober, J. C. Darbord, Q. Launet, M. Deprez, C. Gard, A. Lagarde, J. Mazère, P. Meunier, D. Davas, S. Neuville, N. Préaux, S. Provost, P. Rambourg, J. L. Saubion, and Y. T. Yona. Recommandantion pour la preparation des mélanges de nutrition parentérale. Nutr. Clin. Met. 19:30–55 (2005).

    Google Scholar 

  23. C. L. Ronchera-OMS, N. V. Jimenez, and J. Peidro. Stability of parenteral nutrition admixtures containing organic phosphates. Clin. Nutr. 14:373–380 (1995).

    Article  PubMed  CAS  Google Scholar 

  24. K. Bethune, M. Allwood, C. Grainger, and C. Wormleighton. Use of filters during the preparation and administration of parenteral nutrition. Nutrition. 17(5):403–408 (2001).

    Article  PubMed  CAS  Google Scholar 

  25. P. A. Ball, K. M. Bethune, J. C. Fox, R. Ledger, and M. I. Barnett. Particulate contamination in parenteral nutrition solutions, still cause of concern. Nutrition. 17:926–929 (2001).

    Article  PubMed  CAS  Google Scholar 

  26. F. S. Bettner, and D. J. Stennett. Effects of pH, temperature, concentration and time on particle counts in lipid-containing total parenteral nutrition admixtures. JPEN. J. Parenter. Enteral Nutr. 10:375–380 (1986).

    Article  PubMed  CAS  Google Scholar 

  27. V. A. Parry, K. R. Harrie, and N. L. MCIntosh-Lowe. Effect of various nutrient ratios on the emulsion stability of total nutrient admixtures. Am. J. Hosp. Pharm. 43:3017–3022 (1986).

    PubMed  CAS  Google Scholar 

  28. C. Gellis, A. Arvouet, V. Sautou-Miranda, A. Exbrayat, V. Tramier, S. Corny-Peccoux, and J. Chopineau. Etude préliminaire de hautes concentrations calciques et phosphatées en mélanges ternaires pédiatriques de nutrition parentérale. Nutr. Clin. Metabol. 14:34–46 (2000).

    CAS  Google Scholar 

  29. F. Mangin, D. Brossard, and J. C. Chaumeil. Influence de la concentration en phospholipides d’une émulsion sur la stabilité en mélanges nutritifs complets parentéraux. Journées Corps Gras, réunion commune SNDLF et SFNEP, Tours (1992).

  30. M. Rubin, R. Bilik, A. Aserin, Y. Ziv, Y. Sinai, and M. Dintsman. Catheter obstruction: Analysis of filter content of total nutrient admixture. JPEN. J. Parenter. Enteral Nutr. 6:641–643 (1989).

    Article  Google Scholar 

  31. R. Brown, R. Quercia, and R. Signan. Total nutrient admixtures: a review. JPEN. J. Parenter. Enteral Nutr. 10:650–657 (1986).

    Article  PubMed  CAS  Google Scholar 

  32. C. Washington, A. Athersuch, and D. J. Kynoch. The electrokinetic properties of phospholipid-stabilized fat emulsions. IV- The effect of glucose and pH. Int. J. Pharm. 54:191–197 (1990).

    Article  Google Scholar 

  33. J. C. Chaumeil, F. Devaux, P. Cornette, and D. Brossard. Stabilité et instabilité des mélanges complets pour nutrition parentérale. 5th International Conference on Pharmaceutical Technology, Chateney Malabry, APGI, vol. II, pp 428–434 (1989).

  34. P. A. Ball. Methods of assessing stability of parenteral nutrition regimens. Curr. Opin. Clin. Nutr. Metab. Care. 4:345–349 (2001).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We acknowledge the technical assistance of the medical staff of the neonatology department of the Maternity Centre of Tunis. We are also grateful to Dr Gharbi N. (Laboraoire d’analyses à l’Institut de Neurologie Tunis), to Dr Boubaker A. (immunology department of Pasteur Institute—Tunis), to Touati R. in the Emergency and Anti poison Centre (CAMU)—Tunis, to the OPALIA pharmaceutical laboratory, and.to Pr Zouari B. (Faculté de Médecine de Tunis).

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Authors and Affiliations

  1. Centre National de Greffe de Moelle Osseuse de Tunis, Jebbary Bab Saadoun, 1006, Tunis, Tunisia

    Sonia Chaieb D.

  2. Laboratoire de Pharmacie Galénique, Faculté de Sciences Pharmaceutiques et Biologiques, Université René Descartes, 4 Avenue d l’Observatoire, 75270, Paris Cedex, France

    Jean Claude Chaumeil

  3. Neonatology Department, Maternity Center of Tunis, Bab Saadoun, 1006, Tunis, Tunisia

    Sami Jebnoun & Naima Khrouf

  4. Emergency and Anti Poison Center (CAMU), 40 Division, Montfleury, 1008, Tunis, Tunisia

    Abderrazek Hedhili

  5. Laboratoire de Pharmacie Galénique, Faculté de Pharmacie de Monastir, 5000, Monastir, Tunisia

    Souad Sfar

Authors
  1. Sonia Chaieb D.
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  2. Jean Claude Chaumeil
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  3. Sami Jebnoun
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  4. Naima Khrouf
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Correspondence to Sonia Chaieb D..

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Chaieb D., S., Chaumeil, J.C., Jebnoun, S. et al. Effect of the Intravenous Lipid Emulsions on the Availability of Calcium when using Organic Phosphate in TPN Admixtures. Pharm Res 25, 2545–2554 (2008). https://doi.org/10.1007/s11095-008-9671-7

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  • DOI: https://doi.org/10.1007/s11095-008-9671-7

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