Lipophilic β-adrenoceptor antagonist propranolol increases the hypnotic and anti-nociceptive effects of isoflurane in a swine model

Abstract

BackgroundWe have previously reported that landiolol, an ultra-short-acting β1-adrenoceptor antagonist, does not alter the anaesthetic effects of isoflurane. Here, we investigated the influence of propranolol on the electroencephalographic (EEG) effects and minimum alveolar concentration (MAC) of isoflurane. MethodsFourteen swine [25.0 (sd 4.0) kg] were anaesthetized by isoflurane inhalation. The inhalation concentration was decreased to 0.5% and maintained for 25 min, before being returned to 2%, and maintained for a further 25 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Pharmacodynamic analysis was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequency vs effect-site concentration. After measurement of the EEG effect, MAC was determined using the dew-claw clamp technique, in which movement in response to clamping is recorded. After completion of control measurements, a propranolol 4 mg bolus followed by an infusion (2 mg h−1) was started. After a 30 min stabilization period, the inhalation concentration of isoflurane was varied as in the control period and MAC was re-assessed. ResultsPropranolol shifted the concentration–effect relationship to the left and decreased the effect–site concentration that produced 50% of the maximal effect from 1.30 (0.18) to 1.13 (0.17)%. Propranolol also decreased isoflurane MAC from 1.91 (0.35) to 1.54 (0.32)%. ConclusionsPropranolol alters both the hypnotic and anti-nociceptive effects of isoflurane. In contrast to landiolol, lipophilic β-adrenoceptor antagonists may increase the potency of inhalational anaesthetics.