HEMODYNAMIC, CARDIAC AND NEUROHORMONAL INTERACTIONS OF ESMOLOL AND DEXMEDETOMIDINE IN 36 HEALTHY VOLUNTEERS

Abstract

Introduction. In this randomized, double-blind, placebo-controlled study we evaluated the hemodynamic, cardiac, and neurohumoral interactions of esmolol and dexmedetomidine in normal healthy volunteers. Methods. With IRB approval and written informed consent, thirty-six healthy male or female subjects were randomized into three groups. Dexmedetomidine or placebo was administered in a two-stage infusion that targeted steady-state plasma dexmedetomidine concentrations of 0.0 ng/ml (n=13), 0.3 ng/ml (n=12) and 0.6 ng/ml (n=11). Thirty minutes after study drug administration, subjects were challenged with esmolol (two X 1 mg/kg boluses Q 10 min followed by a continuous infusion of 100 [micro sign]g/kg/min). Hemodynamic and cardiac indices were measured at 0, 30, 40, and 60 minutes. Results. Prior to study drug administration the only significant difference between groups was a lower heart rate in the placebo group. The sympatholytic effects of dexmedetomidine at 0.3 ng/ml and 0.6 ng/ml were evident in the first 30 minutes, lowering heart rate, systemic and pulmonary blood pressures, cardiac output, and plasma catecholamines. Esmolol administration caused a significant decrease in heart rate, systolic pressures and cardiac output only in the placebo group. Esmolol had no significant clinical effects on either of the dexmedetomidine groups. All dexmedetomidine subjects experienced sedation. The sedation was greater in the 0.6 ng/ml than in the 0.3 ng/ml group. Table 1Table 1Discussion. The combination of esmolol and dexmedetomidine was tolerated with no serious drugrelated adverse events. Esmolol significantly reduced cardiac output in the dexmedetomidine placebo group. The effect of esmolol on the hemodynamic and cardiac function of healthy volunteers pre-treated with dexmedetomidine was minimal. We conclude that in healthy volunteers, the interactions between dexmedetomidine and esmolol are clinically insignificant for heart rate and for hemodynamics in both the systemic and pulmonary circulation.