Interaction Of Sedative Effects Of Esketamine And Propofol

Objective:The interaction of sedative effect of esketamine combined with propofol was studied by isobolographic analysis.Methods:A total of 150 patients,aged 18-65 years,BMI 18.5-30kg/m²,ASA I orⅡ,underwent general anesthesia for elective surgery.Patients were randomly divided into three groups by random number table method:propofol group（group P）,esketamine group（group S）and propofol combined with esketamine group（group C）,with 50 cases in each group.Each group was randomly divided into five subgroups with 10 patients in each group.Before formal anesthesia induction,5 subgroups in group P were given propofol 0.80,1.00,1.25,1.56,1.95mg/kg,and 5 subgroups in group S were given esketamine 0.11,0.18,0.30,0.50,0.84mg/kg,respectively.Five subgroups in group C were given propofol and esketamine 0.38/0.10,0.48/0.12,0.60/0.15,0.75/0.19 and0.94/0.24mg/kg,respectively.Ramsay sedation score was evaluated 2 min after administration,and level 6 was considered to have achieved sedation effect.HR,SBP,DBP and Sp O₂before（T₀）and 1（T₁）,2（T₂）and 5（T₃）min after administration were monitored and recorded.Adverse reactions such as respiratory depression,hypertension and hypotension were recorded within 5 min of administration.Half effective dose(ED₅₀)and 95%confidence interval（CI）were determined by point-slope method（comprehensive method）,and the interaction of sedation effect was analyzed by isoradiometric analysis.Results:When the sedative effect was achieved,propofol ED₅₀was 1.2 mg/kg（95%CI1.12-1.29）,esketamine ED₅₀was 0.3 mg/kg（95%CI 0.25-0.37）.In combination group,propofol and esketamine ED₅₀were 0.62/0.16mg/kg（95%CI 0.6/0.14-0.64/0.18）.Compared with the basic value before administration,SBP and DBP in group P were significantly decreased（P<0.05）,HR in group S was significantly increased（P<0.05）,and SBP and DBP were significantly increased（P<0.05）at 1,2 and 5 min after administration.Compared with the basic value before administration,Sp O₂in group P was significantly decreased 2min after administration（P<0.05）,and there was no statistical significance in Sp O₂between groups S and C.Compared with P and S groups,the incidence of adverse reactions in group C was lower（P<0.05）.Isoradiation analysis determined that the combined use of propofol and esketamine at 4∶1 dose ratio was additive.Conclusion:The combination of propofol and esketamine at a dose ratio of 4∶1 is additive after isobolographic analysis.The hemodynamics was more stable and the incidence of adverse reactions was lower in the combination of drugs.