Effect-site concentrations of remifentanil causing bradycardia in hypnotic and non-hypnotic patients

Although the induction of anaesthesia with remifentanil often causes bradycardia, the relationship between the effect-site concentration (Ce) of remifentanil and instantaneous heart rate (HR) has remained unclear. The present study examined the relationship between instantaneous HR and remifentanil Ce at the induction of anaesthesia with and without propofol hypnosis, to facilitate safe management of anaesthesia induction with remifentanil. Instantaneous HR was calculated every 5 s using an electrocardiographic real-time analysis system (MemCalc/Makin2; GMS, Tokyo, Japan). At the beginning of anaesthesia induction, continuous infusion of remifentanil (1 μg min^-1 kg^-1) preceded hypnosis with propofol in 13 patients [non-hypnosis group; mean age, 67.8 (17.5) years], while propofol bolus (30-50 mg) was injected together with continuous remifentanil medication in 18 patients [hypnosis group; mean age, 62.9 (16.5) years]. Remifentanil Ce was estimated every 5 s using the three-compartment model proposed by Minto et al. and the relationship between estimated remifentanil Ce and instantaneous HR was examined. In the hypnosis group, HR was significantly lower than basal HR when remifentanil Ce was increased to 3.5 ng ml^-1 (p < 0.05), whereas no significant HR reduction was found in the non-hypnosis group until remifentanil Ce reached >5 ng ml^-1 (p < 0.05). The induction of anaesthesia using remifentanil with propofol hypnotics significantly reduces HR even in a low remifentanil Ce insufficient to suppress the cardiovascular response at tracheal intubation. Preparations to treat bradycardia are recommended for the safe management of anaesthesia induction when remifentanil is combined with hypnotics.