Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia

Background: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting β₁-receptor antagonist, could reduce the propofol concentration required to prevent movement skin incision. Methods: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 μg · kg^-1 · min^-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 μg · kg_-1 min _-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp₅₀) was calculated by logistic regression. Results: The propofol Cp₅₀ with nitrous oxide was 3.85μg/ml. High-dose esmolol infusion was associated with a significant reduction in the Cp₅₀, to 2.80 μg/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive bias. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found. Conclusions: Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the CP₅₀ reduction. These results demonstrate an anesthetic-sparing effect of a μ-adrenergic antagonist in humans under clinically relevant conditions.