Parenteral structured triglyceride emulsion: safety, tolerance, and effects on nitrogen balance and immunology.

Parenteral structured triglyceride emulsion: Safety, tolerance, and effects on nitrogen balance and immunology. PhD thesis by Joanna Kruimel, Department of Gastroenterology and Hepatology, University Medical Center Nijmegen, The Netherlands, October 6th 2004. Total parenteral nutrition is complete nutrition intravenously administered to patients, incapable of adequate food absorption. An important component in this total parenteral nutrition is the parenteral lipid emulsion. We studied a newly synthesized parenteral lipid emulsion: structured triglycerides. Structured triglycerides consist of triglycerides where the medium-chain and long-chain fatty acids are at random attached to the same glycerol backbone. The aim of our study was to investigate safety, tolerance, and effects on nitrogen balance and immunology of structured triglycerides. We performed a randomized, double-blind trial on 25 moderately catabolic patients, comparing structured triglycerides with a physical mixture of mediumchain and long-chain triglycerides, as part of 5 days post-operative parenteral feeding. No difference in safety and tolerance between the two emulsions was observed. In the patients who completed the study, the mean cumulative nitrogen balance over the first 5 post-operative days was significantly better in the structured triglyceride group (-8 ± 2 g in 10 patients on structured triglycerides and -21 ± 4 g in 9 patients on the physical mixture, p = .015). Structured triglycerides were cleared faster from the blood on the first post-operative day, resulting in lower serum triglyceride levels and lower plasma medium-chain free fatty acid levels, compared with the physical mixture. The effect of structured triglycerides on immunology was studied by measuring the phagocytosing capacity of the mononuclear phagocyte system and the production of cytokines and oxygen radicals. The phagocytosing capacity of the mononuclear phagocyte system (MPS) was studied in 13 patients by measuring the clearance of 99mTc-S-colloid from the blood and did not change during infusion of structured tiglycerides or the physical mixture. The cytokine production was studied in 18 patients: the effect of surgery overwhelmed the effect of nutrition, making conclusions on the effect of the lipid emulsions on cytokine production impossible. Instead, we demonstrated a downregulation of production and release of pro-inflammatory cytokines during surgery. Finally, in-vitro stimulated polymorphonuclear leukocytes from 10 volunteers pre-incubated with the physical mixture showed higher levels of oxygen radicals (p < .005) and faster production of oxygen radicals (p < .005) measuring chemiluminescence, compared with polymorphonuclear leukocytes pre-incubated with structured triglycerides or long-chain triglycerides. High levels of oxygen radicals can be detrimental in case oxygen radicals play a pathogenic role or beneficial when rapid phagocytosis and killing of bacteria is needed. In conclusion, parenteral structured triglyceride emulsion was a safe and welltolerated emulsion, and had a better nitrogen balance and was cleared faster from the blood than the physical mixture. In-vivo phagocytosing capacity of the MPS was not impaired by structured triglycerides or the physical mixture. The interaction of the physical mixture with immune cells differed quite strongly from that of structured triglycerides and long-chain triglycerides, with respect to chemiluminescence. Studies on the clinical relevance of these immunologic observations are needed.