title: Parenteral nutrition admixtures for pediatric patients compounded with highly refined fish oil-based emulsion: assessment of physicochemical stability.
abstract: Fish oil-based emulsion is increasingly used in pediatric patients receiving Parenteral Nutrition (PN). However, its unique use in children on long-term PN is nutritionally debatable as some patients are better off with a mixture of long-chain (LCT) or long-chain + medium-chain (LCT + MCT) triglycerides along with Fish Oil (FO). Lipid emulsions are safely infused when particle diameter ranges between 0.4 and 1.0 micron (like chylomicra), according to European guidelines. No data exist on Fish Oil stability when added to other PN components typically present in pediatric formulations such as other lipids or micronutrients. Our goal is to evaluate the stability of a highly refined FO-emulsion in PN admixtures containing LCT or LCT + MCT triglycerides and different calcium content. Stability studies were carried out on six PN admixtures having two levels of calcium concentration compounded with olive oil LCT + FO, LCT + MCT + FO emulsion and pure FO alone, respectively. The analyses were performed immediately at time 0 (t = 0) and 24, 48, 72, 96 (t = 96) hours after compounding. Particle diameters were determined by Light Scattering-Reverse Fourier Optics Technique by means of a Laser Granulometer. Every sample was stored at 4 °C and triple tested. Statistical significance was verified by f-test. In all admixtures, physicochemical stability did not change between t = 0 and t = 96 and particle diameters were in the expected range of 0.4-1.0 micron provided calcium concentration remained below 4.5 mmol/L. When calcium exceeded that level, 12% of particle diameters was larger than 1.0 micron and 2% exceeded 5.0 micron immediately after compounding. In particular, admixtures compounded with olive oil LCT + FO emulsion or FO emulsion alone showed lower particle diameters compared to admixture with olive/soybean LCT alone, probably due to a different steric encumbrance of oleic acid and omega-3 fatty acid. In the PN admixtures tested, containing FO-emulsion alone or in combination with olive LCT or LCT + MCT, the fat emulsion appears to be stable and safe for infusion when calcium concentration is maintained below 4.5 mmol/L. If calcium level exceeds 4.5 mmol/L, as often required in premature patients, it is advisable to infuse FO emulsion alone through a second intravenous line.
authors.affiliation: Paediatrics, S. Orsola-Malpighi Medical School, Bologna, Italy. Electronic address: luisa.forchielli@unibo.it.
authors.forename: M L
authors.initials: ML
authors.lastname: Forchielli
authors.affiliation: Civil, Environmental and Materials Engineering Department, University of Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonoli
authors.affiliation: Civil, Environmental and Materials Engineering Department, University of Bologna, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Preite
authors.affiliation: Pharmacy Service, S. Orsola-Malpighi Hospital, Medical School, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Stancari
authors.affiliation: Pharmacy Service, S. Orsola-Malpighi Hospital, Medical School, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Maselli
authors.affiliation: Pharmacy Service, S. Orsola-Malpighi Hospital, Medical School, Bologna, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Guarguaglini
authors.affiliation: Pharmacy Service, S. Orsola-Malpighi Hospital, Medical School, Bologna, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Mignini
authors.affiliation: Paediatrics, S. Orsola-Malpighi Medical School, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Masi
authors.affiliation: Pharmacy Service, S. Orsola-Malpighi Hospital, Medical School, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Puggioli
authors.affiliation: Pharmacy Service, S. Orsola-Malpighi Hospital, Medical School, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bersani
mesh_terms: D055598:Chemical Phenomena; D002648:Child; D005217:Fat Emulsions, Intravenous / Q000737:chemistry*; D015525:Fatty Acids, Omega-3 / Q000032:analysis; D005395:Fish Oils / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D019301:Oleic Acid / Q000032:analysis; D000069463:Olive Oil; D010288:Parenteral Nutrition; D010938:Plant Oils / Q000737:chemistry*; D013024:Soybean Oil / Q000737:chemistry*; D014280:Triglycerides / Q000032:analysis
chemical_list: D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D000069463:Olive Oil; D010938:Plant Oils; D014280:Triglycerides; D019301:Oleic Acid; D013024:Soybean Oil
keywords: Calcium concentration; Laser diffraction technique; Omega-3 fatty acids; Stability study