The role of supplemental glutamine on metabolic and endocrine changes in canine patients with critical illness and neoplasia

Abstract

Metabolic and endocrine changes have been documented in canine patients with critical illness and neoplasia. The study was divided into two parts. The first part of the study investigated endogenous protein synthesis (PSR), urinary loss of nitrogen, glucose flux, resting energy expenditure (REE), and respiratory quotient (RQ) in fifteen dogs with osteosarcoma (OSA) and 11 healthy female beagle dogs using stable isotope tracer (15N -glycine, 6.6-deuterium-glucose) and indirect calorimetry techniques. Indirect calorimetry was performed before and after limb amputation surgery. Twenty-four hours after surgery, infusions of stable isotope tracers (4.5 mg/kg 15N-gIycine intravenous bolus, and 6.6-deuterium-glucose 4.5 mg/kg IV bolus, followed by 1.5 mg/kg hour as a constant rate infusion for 3 hours) was performed. Blood samples were obtained before the start of stable isotope infusion, and at 3 and 10 hours after infusion. Urine was collected for ten hours after infusion of tracers, and a pooled urine sample was used for sample analysis. Mass spectroscopy was utilized to measure the isotope or its metabolites in the serum and urine, then endogenous protein synthesis, urinary loss of nitrogen, and glucose flux were calculated using lean body mass values obtained from a dual energy x-ray absorptiometry examination performed on each patient while under general anesthesia. Dogs with OSA had statistically higher REE in the pre, but not post-operative time periods. There was no significant difference in RQ from dogs with OSA before or after surgery, and the healthy beagle controls. Post-operatively. dogs with OSA had significantly lower rates of endogenous protein synthesis, higher urinary loss of nitrogen, and greater glucose flux than the healthy beagle controls, indicating alterations in nitrogen balance and carbohydrate flux.

The second part of the study was performed on 36 dogs with a variety of critical illnesses and neoplasia (6 sepsis, 5 trauma, 12 surgery, 13 neoplasia) before and after 48 hours of supplemental enteral feeding with or without additional supplemental L-glutamine powder. The hypothalamic-pituitary-thyroid and -adrenal axes were examined in the pre- and post-feeding time periods by measuring endogenous thyroid stimulating hormone (eTSH), total thyroxine (T4) and ACTH stimulation tests using 0.25 mg patient IV Cosyntropin. Basal energy requirements (BER) were calculated using the formula (30 x body weight m kg) - 70 = kcaL/day BER. Stable isotope tracer analyses were performed in an identical manner as that performed on the dogs with OSA before and after 48 hours of supplemental enteral feeding. Patients were also randomly assigned to receive L-glutamine powder (0.24 g/kg day) supplementation in excess of that found in the liquid enteral diet. A p-value of p < 0.05 was set as a level of significance. A Kolmogorov-Smirnov test was performed to assess normality of distribution of data. The data were normally distributed. Bartlett’s test of homogeneity was performed to assess normality of variances of data. The variances were not homogeneous, and were log transformed for further statistical comparison. After log transformation of the data, an analysis of variance, with Fisher's Least Significant Difference Test were performed for treatment effects and individual means comparisons. There was no significant difference in eTSH or T4 values across disease categories, before or after supplemental feeding. Glutamine had no effect on thyroid axis function in any disease category. Euthyroid sick syndrome, characterized by low or normal eTSH and low T4, was observed in 41.6% of patients before feeding, and 60% of patients after feeding. No significant difference in adrenocortical function was observed in any disease category. Glutamine supplem entation had no effect on adrenocortical axis function. Endogenous protein synthesis was not statistically lower in any disease category before or after supplemental nutrition. Patients with sepsis had higher PSR after supplemental feeding. Overall urinary nitrogen loss statistically decreased in the post-feeding time period. Glutamine supplementation had no significant effect on PSR or urinary loss of nitrogen in any disease category. Glucose flux was not significantly lower in any disease category before or after supplemental feeding. Glutamine had no effect on glucose flux. The second part of the study demonstrated that euthyroid sick syndrome is a common occurrence in canine patients with critical illness and neoplasia, and that supplemental nutrition may prevent negative nitrogen balance during the course of illness and treatment.