Median effective dose of remimazolam for the induction of deep sedation in ICU patients during prone position ventilation

Zhao Jieyu; Zheng Xiangde; Liu Cheng; He Jiangshan; Zhou Wenlai

doi:10.3969/j.issn.1002-1949.2024.02.005

Abstract：Objective To determine the median effective dose(ED50)of remimazolam for the induction of deep sedation in ICU patients during prone position ventilation(PPV).Methods Forty-five patients with early moderate/severe ARDS in ICU of Dazhou Central Hospital from November 2022 to July 2023 underwent deep sedation during prone position ventilation were selected.First sufentanil was administered at dose of 0.4 μg/kg until the critical-care pain observation tool(CPOT)score reached 0-1,remimazolam was given to induce sedation until standard sedation,and the prone position ventilation was performed.The dose of remimazolam for the induction of deep sedation was determined by the modified Dixon sequential test method.The initial dose of remimazolam was determined to be 0.2 mg/kg according to the preliminary test,with a gradient of 0.025 mg/kg.Standard sedation was defined as Richmondagitation-sedation scale(RASS)≤-4 and spectral entropy(SE)≤50 within3 minutes after administration.However,if there were RASS>-4,SE>50 and the reactions such as body movement,frowning,tearing,coughing,swallowing within 3 minutes after the beginning of prone position ventilation,it was still defined as unsatisfactory sedation.When standard and satisfactory sedation was achieved,the next patient decreased a gradient from the dose of the previous patient.If the sedation was substandard or unsatisfactory,the dose of the next patient would increase by a gradient.The study was terminated after 10 consecutive up and down cycles.The ED50 and 95%effective dose(ED95)of remimazolam were calculated by Probit regression analysis.The changes of heart rate(HR),respiratory rate(RR),mean arterial pressure(MAP)and pulse oxygen saturation(SpO2)were recorded before and after administration,as well as the occurrence of nausea and vomiting,bradycardia and other adverse reactions were recorded.Results The ED50 and ED95 of remimazolam for the induction of deep sedation in ICU patients during prone position ventilation were 0.228 mg/kg(95%CI 0.208-0.248)and 0.365 mg/kg(95%CI 0.299-0.518).Compared with the standard sedation of sufentanil(T1),SpO2 were not changed 2 min after remimazolam injection(T2)and 2 min after prone position ventilation(T3)(P>0.05).At T3,HR,MAP and RR were lower than those at T1 and T2(P<0.05),but the decrease was within20%.Sedation indexes such as RASS and SE at T2 and T3 decreased significantly compared with T1(P<0.01).During the induction of deep sedation,three patients had hypotension and ephedrine was effective,two patients had bradycardia and atropine was effective,and there were no other adverse effects.Conclusions The ED50 and ED95 of remimazolam for the induction of deep sedation in ICU patients during prone position ventilation were 0.228 mg/kg and 0.365 mg/kg.Futhermore it can provide adequate sedation with few haemodynamic,respiratory and other side adverse reactions.