Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man.

TLDR

The study aimed to determine the plasma epinephrine thresholds for its metabolic and hemodynamic actions and its metabolic clearance rates. This was achieved by administering 60‑minute intravenous epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 µg min⁻¹ to six normal human subjects. Thirty infusions produced steady‑state plasma epinephrine concentrations of 24–1,020 pg ml⁻¹, with thresholds of 50–100 pg ml⁻¹ for heart rate, 75–125 pg ml⁻¹ for blood glycerol and systolic blood pressure, 150–200 pg ml⁻¹ for glucose, lactate, beta‑hydroxybutyrate, and diastolic blood pressure, and >400 pg ml⁻¹ for early insulin decrements; no changes in alanine, glucagon, growth hormone, or cortisol were detected, the metabolic clearance rate rose from 52 ± 4 to 89 ± 6 ml min⁻¹ kg⁻¹ as concentrations increased, and epinephrine proved ten times more potent than norepinephrine.

Abstract

To determine the plasma epinephrine thresholds for its metabolic and hemodynamic actions and plasma epinephrine metabolic clearance rates, 60-min intravenous epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min were performed in each of six normal human subjects. These 30 infusions resulted in steady-state plasma epinephrine concentrations ranging from 24 to 1,020 pg/ml. Plasma epinephrine thresholds were 50-100 pg/ml for increments in heart rate, 75-125 pg/ml for increments in blood glycerol and systolic blood pressure, 150-200 pg/ml for increments in plasma glucose (the resultant of increments in glucose production and decrements in glucose clearance), blood lactate, blood beta-hydroxybutyrate, and diastolic blood pressure, and greater than 400 pg/ml for early decrements in plasma insulin. Changes in blood alanine, plasma glucagon, plasma growth hormone, and plasma cortisol were not detected. At steady-state plasma epinephrine concentrations of 24-74 pg/ml, values overlapping the basal normal range, the mean (+/-SE) plasma metabolic clearance rate of epinephrine was 52 +/- 4 ml x min-1 x kg-1; this value rose to 89 +/- 6 ml x min-1 x kg-1 (P less than 0.01) at steady-state epinephrine concentrations of 90-1,020 pg/ml. We conclude that in human subjects: (a) the plasma epinephrine thresholds for its hemodynamic and metabolic actions lie within the physiologic range, (b) epinephrine and norepinephrine accelerate their own metabolic clearance, and (c) epinephrine is 10 times more potent than norepinephrine.