瑞马唑仑用于重症监护病房俯卧位通气深镇静诱导的半数有效剂量

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

目的测定瑞马唑仑用于重症监护病房(ICU)患者俯卧位通气深镇静诱导的半数有效剂量(ED50)。方法选择2022年11月至2023年7月达州市中心医院收入ICU的早期中、重度急性呼吸窘迫综合征(ARDS)行俯卧位通气深镇静患者45例,给药舒芬太尼0.4μg/kg使重症监护疼痛观察工具(CPOT)评分达0~1分后,使用瑞马唑仑诱导镇静,镇静达标后开始俯卧位通气。瑞马唑仑诱导镇静的剂量由改良Dixon序贯试验法确定,根据预试验确定瑞马唑仑的起始剂量为0.2 mg/kg,剂量梯度为0.025 mg/kg。镇静达标定义为给药后3 min内Richmond躁动-镇静评分(RASS)≤-4分且光谱熵(SE)≤50。但如俯卧位通气3 min之内出现明显的体动、皱眉、流泪、呛咳和吞咽等反应且RASS>-4分或SE>50,仍表示镇静不理想。镇静达标且理想则下一例患者在上一例的给药剂量基础上降低一个梯度,若镇静未达标或不理想,下一例给药剂量升高一个梯度。连续出现10次交叉后终止研究。运用Probit回归分析法,计算出瑞马唑仑的ED50和95%有效剂量(ED95)。记录给药前后心率(HR)、呼吸频率(RR)、平均动脉压(MAP)、血氧饱和度(SpO_(2))及俯卧位通气中心动过缓和恶心呕吐等不良反应的发生情况。结果瑞马唑仑用于ICU患者俯卧位通气深镇静诱导的ED50为0.228 mg/kg(95%CI 0.208~0.248),ED95为0.365 mg/kg(95%CI 0.299-0.518)。与舒芬太尼镇痛达标后(T_(1))比较,瑞马唑仑诱导镇静后2 min(T_(2))和俯卧位通气后2 min(T_(3))各时间点的血氧饱和度(SpO_(2))差异无统计学意义(P>0.05);T_(3)时HR、MAP及RR较T_(1)和T_(2)时均有下降(P<0.05),但下降幅度在20%以内;T_(2)和T_(3)时镇静深度指标RASS及SE比T_(1)时显著下降(P<0.01)。诱导期间3例患者出现低血压,给予麻黄碱有效;2例患者出现心动过缓,给予阿托品有效,无其他不良反应。结论瑞马唑仑用于ICU患者俯卧位通气深镇静诱导的ED50为0.228 mg/kg,ED95为0.365 mg/kg,镇静效果确切,呼吸循环影响较小,不良反应少。

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 0.4μg/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 Richmond agitation-sedation scale(RASS)≤-4 and spectral entropy(SE)≤50 within 3 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(SpO_(2))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(T_(1)),SpO_(2) were not changed 2 min after remimazolam injection(T_(2))and 2 min after prone position ventilation(T_(3))(P>0.05).At T_(3),HR,MAP and RR were lower than those at T_(1) and T_(2)(P<0.05),but the decrease was within 20%.Sedation indexes such as RASS and SE at T_(2) and T_(3) decreased significantly compared with T_(1)(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.