RELATIONSHIP BETWEEN INFUSION RATES, PLASMA-CONCENTRATIONS, AND CARDIOVASCULAR AND METABOLIC EFFECTS DURING THE INFUSION OF NOREPINEPHRINE IN HEALTHY-VOLUNTEERS

Objective: To determine the relationship between iv infusion rate, plasma concentrations, and hemodynamic and metabolic actions of norepinephrine. Design: Norepinephrine was administered by using five iv infusion rates (0.01 to 0.2-mu-g/kg/min) for 30 mins each to eight volunteers, for the purpose of constructing cumulative plasma concentration-response curves. Setting: Laboratory of the Department of Anesthesiology at a university hospital. Measurements and Main Results: Systolic and diastolic BP, heart rate, and the plasma concentrations of norepinephrine, glucose, nonesterified fatty acids, and insulin were measured at the end of each infusion rate. During the highest infusion rate, plasma norepinephrine concentrations increased from 199 +/- 75 to 7475 +/-1071 pg/mL (1.18 +/- 0.44 to 44.18 +/- 6.33 nmol/L). Typical hemodynamic responses, such as increases in BP and decreases in heart rate, were seen, while the plasma concentrations of glucose and nonesterified fatty acids increased from 92 +/-10 to 132 +/- 17 mg/dL (5.1 +/- 0.6 to 7.3 +/- 0.9 mmol/L) and 11 +/- 4 to 34 +/- 6 mg/dL (0.11 +/- 0.04 to 0.34 +/- 0.06 g(L), respectively, during the 0.2-mu-g/kg/min infusion rate (p<.05). Despite the increase in glucose concentration, insulin remained at baseline values. Metabolic and hemodynamic effects occurred at similar plasma concentrations throughout the study. Conclusions: Administration of norepinephrine showed no selective hemodynamic actions. The metabolic responses observed in this investigation were similar to those responses seen during increased endogenous sympathetic nervous system activity, such as stress, exercise, or trauma.