Abstract
Objective
To determine the magnitude and time course of adrenergic effects on metabolism in volunteers and possible implications for the use of sympathomimetics in the critically ill.
Design
Descriptive laboratory investigation.
Subjects
7 volunteers.
Intervention
Primed continuous infusions of stable isotope tracers ([15N2]-urea, [6,6-D2]-glucose, [methyl-D3]-L-leucine, [15N]-L-alanine) were used. After isotopic steady state had been reached an infusion of adrenaline (0.1 μg/kg/min) was administered (4 h). Isotopic enrichment was measured using gas chromatography-mass spectrometry and the corresponding rates of appearance were calculated.
Measurements and main results
Glucose production increased from 14.1±1.2 to 21.5±2.0 μmol/kg/min (p<0.05) after 80 min of adrenergic stimulation and then decreased again to 17.9±1.2 μmol/kg/min after 240 min. Leucine and ketoisocaproate (KIC) fluxes were 2.3±0.2 and 2.6±0.2 μmol/kg/min, respectively, at baseline and gradually decreased to 1.8±0.2 and 2.2±0.1 μmol/kg/min, respectively, after 240 min of adrenaline infusion (bothp<0.05). Alanine flux increased from 3.7±0.5 to 6.9±0.9 μmol/kg/min (p<0.05) after 80 min of adrenergic stimulation. Urea production slightly decreased from 4.8±0.9 to 4.3±0.8 μmol/kg/min during adrenaline (p<0.05).
Conclusions
Adrenaline induced an increase in glucose production lasting for longer than 240 min. The decrease in leucine and KIC flux suggests a reduction in proteolysis, which was supported by the decrease in urea production. The increase in alanine flux is therefore most likely due to an increase in de-novo synthesis. The ammonia donor for alanine synthesis in peripheral tissues and the target for ammonia after alanine deamination in the liver remain to be investigated. These results indicate that adrenaline infusion most probably will not promote already enhanced proteolysis in critically ill patients. Gluconeogenesis is an energy consuming process and an increase may deteriorate hepatic oxygen balance in patients.
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Ensinger, H., Träger, K., Geisser, W. et al. Glucose and urea production and leucine, ketoisocaproate and alanine fluxes at supraphysiological plasma adrenaline concentrations in volunteers. Intensive Care Med 20, 113–118 (1994). https://doi.org/10.1007/BF01707665
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DOI: https://doi.org/10.1007/BF01707665