Missing evidence for toxicity of high PFAT5 levels in mixtures of lipids

Summary Background The compliance of lipid admixtures to physical emulsion stability parameters is extremely important to ensure the safety of patients. For example, admixtures containing a percentage of fat globules larger than 5 μm in diameter (concept known as PFAT5) of more than 0.05% might produce toxic effects in lung and liver. This concern is mainly based on a limited number of animal studies investigating admixtures with high PFAT5 levels resulting from 48 h of admixture storage. However, all effects observed in these studies might as well be attributed to chemical instability like lipid oxidation, which was not analysed and therefore could not be excluded. Aims This study aims at investigating the correlation of high levels of PFAT5 in lipid emulsion admixtures with lipid oxidation parameters under different storage conditions. Methods We studied the physical (PFAT5 value) as well as the chemical (pH, primary and secondary oxidation parameters) stability of an admixture of a lipid emulsion and an amino acid solution after up to 48 h following different storage conditions (exposure to oxygen, exposure to artificial light). Results High levels of PFAT5 were only observed after exposure of the admixture to oxygen. Additional exposure to artificial light led to a parallel increase in the primary and secondary oxidation parameters, while the pH was unchanged. Conclusions The admixtures investigated in the former animal studies were obviously both physically and chemically unstable and all effects observed in the studies could just as well be caused by chemical instability, namely the administration of lipid peroxides with the admixture.