Dexamethasone increases plasma amino acid concentrations in bronchopulmonary dysplasia.

Abstract

Nine ventilated low birthweight babies were treated with dexamethasone (0-6 mg/kg/day). Appreciable suppression of weight gain was accompanied by uraemia and significant increases in the concentration of ali amino acids except phenylalanine, tyrosine, threonine, and glutamate. Ornithine, citrulline, alanine, glutamine, and cystine concentrations increased threefold or more. The findings could not be explained by changes in dietary intake and presumably reflect pronounced catabolism, though the effects of dexamethasone on, intermediary metabolism and membrane transport could also play a part.Dexamethasone is used increasingly to treat infants with bronchopulmonary dysplasia, principally to facilitate the withdrawal of mechanical respiratory support. ' 2 The precise mode of action of this drug in bronchopulmonary dysplasia is not clear, but lung compliance is known to increase, possibly through clearance of interstitial oedema. Treatment, which may be given for six weeks or more,' is usually accompanied by suppression of weight gain and uraemia, indicating the presence of catabolism.3 The metabolic vulnerability of immature infants provided with protein in excess of growth requirements is well known,47 but there are no data about the metabolic effects of high dose corticosteroid treatment in this group of patients. In this study we have measured the effect of dexamethasone on plasma amino acid concentrations.

Whole Body Lean Mass Is Altered by Dexamethasone Treatment through Reductions in Protein and Energy Utilization in Piglets

“…Infants receiving dexamethasone also have elevated blood urea nitrogen and reduced nitrogen re tention associated with reduced growth and lean body mass [7], Recently, leucine kinetic studies in dexamethasone-treated infants [10] and piglets [11] have demonstrated that our observed reductions in lean body mass are likely due to elevations in protein catabolism rather than reductions in protein anabolism. In infants, protein turnover was elevated dur ing high doses (0.35 mg/kg/day) of dexameth asone [10] which were lower than those re ceived by the piglets and in other infant stud ies [6,7]. Administration of dexamethasone (5 mg/kg/day) to piglets at doses ten times in excess of those given to human infants in duces protein catabolism in parallel to that observed in infants [11].…”

“…The long-term benefits of steroids in reducing morbidity in this clinical population arc not as clearly defined [4,5]. While dexametha sone is now common therapy for premature infants with chronic lung disease [3], doses of this steroid which are used to improve lung function arc also capable of reducing neonatal growth [6][7][8][9], Furthermore, dexaméthasone therapy induces muscle protein catabolism [7,10] as indicated biochemically in infants re ceiving dexamethasone and by elevated leu cine turnover and oxidation in piglets using l3C-lcucine tracers [11]. However, the extent of protein catabolism and the effect on depo sition of whole body lean mass has not been investigated.…”

Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange

“…Developmental changes in the effect of dexamethasone on amino acid transport and metabolism have been previously noted. In newborn babies (15,20) and in newborn rats (8), dexamethasone infusion causes a marked increase in the plasma concentration of several amino acids, glutamine and alanine included, whereas in adult men (21), it causes no significant concentration changes, with the exception of a small increase in alanine. In contrast to hepatocytes isolated from adult rats, fetal rat hepatocytes do not respond to dexamethasone with an increase in system A-mediated transport (9).…”

Dexamethasone does not affect vasopressin release in bronchopulmonary dysplasia

“…All infants gained weight before and during the study period; however, the average weight gain before steroid initiation was greater than that observed during steroid therapy. This finding could be due not only to a dehydration effect, but to an increase in protein catabolism, resulting in the breakdown of structural protein [24][25][26].…”