Effects of different doses of dexmedetomidine on EC50 of propofol given by target-controlled infusion at loss of consciousness

Abstract

Objective To evaluate the effects of different doses of dexmedetomidine on the median effective concentration (EC50) of propofol given by target-controlled infusion (TCI) at loss of consciousness (LOC).Methods Eighty ASA Ⅰ or Ⅱ patients of both sexes,aged 18-64 yr,with body mass index ≤25 kg/m2,scheduled for operations under general anesthesia,were randomly allocated to one of four groups(n=20 each): control group (group C) and dexmedetomidine 0.4 μg/kg group (group D1),dexmedetomidine 0.5 μg/kg group (group D2) and dexmedetomidine 0.6 μg/kg group (group D3).Dexmedetomidine 0.4,0.5 and 0.6 μg/kg were infused intravenously over 10 min in groups D1-3,while the equal volume of normal saline was given instead of dexmedetomidine in group C.Propofol was then given by TCI and the EC50 was determined by up-and-down sequential trial.The target plasma concentration was set at 2.0μg/ml in the first patient in each group.The ratio of the target plasma concentration between the two consecutive patients was 1.1.Loss of response to eyelash stimulation and verbal command (2 times) was considered to be signs of LOC.The EC50 and 95％ confidence interval (CI) of propofol causing LOC were calculated.Complications such as bradycardia,hypotension and respiratory depression were recorded.Results The EC50 (95％ CI) of propofol causing LOC was 2.59 (2.51-2.67),2.09 (2.02-2.16),1.82 (1.70-1.95) and 1.60 (1.49-1.72) μg/ml in groups C and D1.3 respectively.The EC50 of propofol causing LOC was significantly lower in groups D1-3 than in group C.Dexmedetomidine significantly decreased the EC50 of propofol required for causing LOC in a dose-dependent manner in groups D1-3 (P ＜ 0.05).The incidences of bradycardia and hypotension were significantly lower in groups D1.3 than in group C (P ＜ 0.05).Compared with group D1,the incidence of bradycardia was increased in groups D2,3 and the incidence of hypotension was increased in group D3 (P ＜ 0.05),There was no significant difference in the incidences of bradycardia and hypotension between groups D2 and D3 (P ＞ 0.05).No patients developed respiratory depression.Conclusion The optimum dose for dexmedetomidine infused intravenously when combined with propofol given by TCI is 0.4 μg/kg and it can decrease the EC50 of propofol administered by TCI at LOC with no adverse reactions. Key words: Dexmedetomidine; Propofol; Drug delivery systems; Dose-response relationship,drug