Relationship between infusion rates, plasma concentrations, and cardiovascular and metabolic effects during the infusion of norepinephrine in healthy volunteers

OBJECTIVETo determine the relationship between iv infusion rate, plasma concentrations, and hemodynamic and metabolic actions of norepinephrine. DESIGNNorepinephrine was administered by using five iv infusion rates (0.01 to 0.2 μg/kg/min) for 30 mins each to eight volunteers, for the purpose of constructing cumulative plasma concentration-response curves. SETTINGLaboratory of the Department of Anesthesiology at a university hospital. MEASUREMENTS AND MAIN RESULTSSystolic and diastolic BP, heart rate, and the plasma concentrations of norepinephrine, glucose, non-esterified 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 μg/kg/min infusion rate (p