Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis in response to endotoxemia in parenterally fed rats

Objective: This study compared the effect of different doses of octreotide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions. Methods: Sixty-six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 mu g/kg/day (LPS + Oct 10), 100 mu g/kg/day (LPS + Oct 100), or 1000 mu g/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil per os except for water ad libitum. Nitrogen balance, urinary 3-methylhistidine/creatinine ratio, serum glucose concentration, and incidence of glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's multiple range test, and Fisher's Exact Test were used for statistical analysis. Results: Nitrogen balance (mg/48 hours) was significantly lower in all four groups receiving LPS +/- Oct when compared to the control group receiving PN alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/- Oct when compared to control. There were no statistically significant differences in nitrogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio of urinary 3-methylhistidine/creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/- 0.37 vs. 0.42 +/- 0.24, p < 0.05). Serum glucose concentrations and incidence of glycosuria among the five groups were not significantly different. Conclusions: Endotoxin significantly reduces nitrogen balance compared to controls fed PN. Octreotide does not significantly improve nitrogen retention or glucose homeostasis in endotoxemic parenterally fed rats.