A Pharmacodynamic Study Of Target-controlled Infusion Of Dexmedetomidine And Propofol During Anesthesia Induction

ObjectiveTo investigate the effects of target-controlled infusion(TCI)of dexmedetomidine on the effect-site median effective concentration(EC50)of propofol at loss of consciousness(LOC)in patients,and the hypnotic interaction between dexmedetomidine and propofol.Methods(1)Sixty-four patients,20~60 years,scheduled for elective surgery were randomly allocated to receive dexmedetomidine of 0.0 ng/ml(group A),dexmedetomidine of 0.4 ng/ml(group B),dexmedetomidine of 0.6 ng/ml(group C)and dexmedetomidine of 0.8 ng/ml(group D)for 15 min before propofol infusion by TCI.The propofol infusion was started to provide an effect-site concentration of 1.0 ?g/ml,and increased by 0.2 ?g/ml when propofol effect-site concentration and target concentration were in equilibrium until LOC.The effect-site concentration of propofol,BIS and adverse events were recorded in four groups,and the effect-site EC50(95%CI)at LOC was calculated by probit regression method.(2)Sixty male patients,20~50 years,scheduled for elective surgery were randomly allocated to receive dexmedetomidine at a dose of 0.0 ng/ml(group A),dexmedetomidine at a dose of 0.4 ng/ml(group B),dexmedetomidine at a dose of 0.6 ng/ml(group C),and dexmedetomidine at a dose of 0.8 ng/ml(group D).Sixty female patients,20~50 years,scheduled for elective surgery were also randomly assigned to groups A,B,C,and D.Propofol was administered after dexmedetomidine had been infused intravenously for 15 minutes.The propofol infusion was started to provide an effect-site concentration of 1.0 ?g/ml,and increased by 0.2 ?g/ml when propofol effect-site concentration and target concentration were in equilibrium until LOC.The hypnotic interaction between dexmedetomidine and propofol was determined by using the model of pharmacodynamic interaction.Results(1)The effect-site EC50(95%CI)at LOC in groups A,B,C and D were 2.30(2.24~2.36)?g/ml,1.92(1.87~1.96)?g/ml,1.60(1.55~1.65)?g/ml and 1.41(1.35~1.45)?g/ml,respectively.There was a negative correlation between the effect-site concentration of propofol-induced LOC and target concentration of dexmedetomidine(r =-0.84,P < 0.01).Compared with groups A,B and C,the incidence of bradycardia was higher in group D(P < 0.05).Compared with groups A and B,the incidences of propofol injection pain were lower in groups C and D(P < 0.05).(2)No significant differences were found between the residual sum of squares(RSS)of the models exploring the possibility of a nonadditive or additive interaction between dexmedetomidine and propofol for male patients(P>0.05).The RSS of the model exploring the possibility of an additive interaction between dexmedetomidine and propofol for female patients was similar to that of the model exploring the possibility of a nonadditive interaction(P>0.05).Conclusion1.The effect-site EC50 of propofol-induced LOC gradually decreases with increasing target concentration of dexmedetomidine.2.Combining propofol and dexmedetomidine of 0.4 or 0.6 ng/ml can reduce the effect-site EC50 of propofol-induced LOC with a lower incidence of bradycardia.3.Dexmedetomidine of 0.6 or 0.8 ng/ml can reduce the incidence of propofol injection pain.4.Combining propofol with 0.6 ng/ml dexmedetomidine brings about less adverse events and stable hemodynamics during anesthesia induction.5.The hypnotic interaction between dexmedetomidine and propofol shows additive effect,regardless of gender.