EFFECTS OF INTRAVENOUS LIPID AS A SOURCE OF ENERGY IN PARENTERAL-NUTRITION ASSOCIATED HEPATIC-DYSFUNCTION AND LIDOCAINE ELIMINATION - A STUDY USING ISOLATED RAT-LIVER PERFUSION

The effects on liver function and hepatic lidocaine elimination using 20% Intralipid(R) as source of non-protein calories (30%) in parentera l nutrition were studied using an isolated rat liver perfusion procedu re. Rats were randomly assigned to one of the three treatment groups: PNL group (n = 6), consisting of 16.94% dextrose, 2.46% Intralipid(R), and 5.2% amino acids; PN group (n = 5): consisting of 24.2% dextrose and 5.2% amino acids; and CF group (n = 6), chow fed (rat chow and wat er). The rate of lidocaine metabolism was significantly reduced after 7 d in the two PN treated groups when compared to CF. Steatosis was ob served in five out of six PNL treated animals and two out of five PN t reated animals. Intrinsic clearance was reduced by 80% in the PNL grou p and by 60% in the PN animals (p < 0.05). Molar metabolite to drug ra tios revealed significant reductions in N-dealkylation, m-hydroxylatio n, and aryl methyl hydroxylation in groups PNL and PN; these values am ounted to 67-92% (p < 0.05). These findings suggest that a dextrose-am ino acid solution induced steatosis and reduced the rate of lidocaine metabolism. The incorporation of Intralipid(R) caused further deterior ation. (C) 1997 John Wiley & Sons, Ltd.