Effective dose of remimazolam combined with etomidate for general anesthesia induction by BCD method
Objective To determine the median and 95 percent effective doses(ED50 and ED95)of remimazolam combined with etomidate for general anesthesia induction by the biased coin design(BCD)method in two stages.Methods One hundred and four patients taking general anesthesia by tracheal intubation at Affiliated Hospital of Guangdong Medical University from September 1,2022 to October 31,2023 were selected,and were divided in two stages(group S1 and group S2)for the BCD experiment;they were 18-64 years old.In group S1,the fixed dose of etomidate was set as 0.15 mg/kg;the first patient was given remimazolam 0.25 mg/kg;when the patient was not conscious,the score of alertness/sedation(OAA/S)≤1,and bispectral index(BIS)60,the patient was given sufentanil 0.4 μg/kg and atracurium 0.2 mg/kg;the ED50 and ED95 of remimazolam for the next patient were determined by the BCD method based on the situation of tracheal tube insertion in the previous patient.Similarly,the ED50 of remimazolam was fixed in group S2,and the ED50 and ED95 of etomidate were measured.The cardiovascular response to tracheal intubation before induction(T0)and before(T1)and 1(T2)and 3 min(T3)after intubation and the incidences of hypotension,bradycardia,muscle tremors,hiccup,injection pain,etc.were recorded.The repeated measurement analysis of variance,x2 test,and Fisher exact probability were applied.According to the dosage of medication,the effective dose and 95％confidence interval(CI)were calculated by the Probit probability unit method.Results There were 52 cases in group S1,including 21 males and 31 females;they were(40.7±12.2)years old;their body mass index(BMI)was(22.8±3.1)kg/m2;there were 11 cases of grade Ⅰ and 41 cases of grade Ⅱ of American Society of Anesthesiologists(ASA).There were 52 cases in group S2,including 27 cases and 25 cases;they were(39.7±12.7)years old;their BMI was(22.4±2.8)kg/m2;there were 3 cases of grade Ⅰ and 49 cases of grade Ⅱ of ASA.When 0.15 mg/kg etomidate was used for the general anesthesia induction,the ED50 and ED95 of remimazolam required to prevent cardiovascular response to tracheal intubation were 0.253 mg/kg(95％CI 0.130-0.265 mg/kg)and 0.285 mg/kg(95％CI 0.276-0.352 mg/kg),respectively.The ED50 and ED95 of etomidate combined with remimazolam(0.25 mg/kg)required to prevent cardiovascular response to tracheal intubation were 0.191 mg/kg(95％CI 0.084-0.212 mg/kg)and 0.254 mg/kg(95％CI 0.234-0.413 mg/kg),respectively.There were no statistical differences in HR at T0,T1,T3 between the two groups(all P＞0.05).The HR at T2 was higher than that at T0(all P＜0.05).The MAP's at T0 and T2 were higher than those at T1 and T3,with statistical differences(all P＜0.05).The was no statistical difference in MAP between at T0 and T2(all P＞0.05).No bradycardia occurred in both groups.All the patients had successful intubation at one time.There were statistical differences in the incidences of injection pain and hiccup between group S1 and group S2[17.3％(9/52)vs.0 and 11.5％(6/52)vs.0;both P＜0.05).There was no statistical difference in the incidences of muscle tremors and hypotension between the two groups(both P＞0.05).Conclusion Remimazolam combined with etomidate is safely and effective for endotracheal intubation in the 18 to 64 years old.The ED50 and ED95 of remimazolam can provide references for precision medication in clinic when it is combined with etomidate.
万方数据
维普
