METABOLIC STRESS MODIFIES THE THERMOGENIC EFFECT OF DOBUTAMINE IN MAN

Objective: To study if metabolic stress modifies the thermogenic effect of dobutamine. Design: Prospective, increasing dose, pharmacologic study. Setting: Laboratory of the Department of Intensive Care Unit at a university hospital. Subjects: Twelve normal volunteers. Interventions: Dobutamine hydrochloride was infused to 12 healthy male volunteers starting at a dose of 2 mu g/min/kg and gradually increased to 4 and 6 mu g/min/kg. Each dose of dobutamine was infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers using a triple hormone infusion (epinephrine, cortisol, and glucagon) before dobutamine, and was continued at a constant rate during the dobutamine infusion. The remaining six volunteers served as the control group and received only dobutamine. Measurements and Main Results: Oxygen consumption (VO2) was measured using a metabolic monitor. Arterial blood pressure was measured noninvasively, and cardiac output was monitored by Doppler echocardiography. Plasma concentrations of dopamine, norepinephrine, and epinephrine were measured in both groups. In the triple hormone group, blood was sampled to measure concentrations of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the presence of a metabolic stress reaction. At the maximum dose, dobutamine induced a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m(2)) in VO2 in the control group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m(2)) in the triple hormone group (p < .05 between the two groups) compared with baseline. No change in the respiratory exchange ratio was seen. The triple hormone infusion alone induced hypermetabolism, a marked hemodynamic response, and increased lipolysis. Conclusions: Stress, induced by a triple hormone infusion, diminishes the thermogenic effect of dobutamine. In the clinical setting, a >10% to 15% increase in VO2 in response to dobutamine may not be explained just by the thermogenic effect of the drug.