利多卡因联用对行包皮环切术患儿所需艾司氯胺酮半数有效量的影响

Effect of lidocaine on median effective dose of esketamine for children undergoing circumcision

目的·探索利多卡因联用对行包皮环切术所需艾司氯胺酮半数有效量(median effective dose,ED_(50))的影响,评估其对儿童心血管的稳定性。方法·采用序贯法纳入上海交通大学医学院附属上海儿童医学中心2021年4月—6月在艾司氯胺酮静脉麻醉下行包皮环切术的3~7岁患儿,艾司氯胺酮给药后静脉注射0.5%利多卡因1.5 mg/kg再行手术,计算与利多卡因联用时行儿童包皮环切术所需的艾司氯胺酮ED_(50),并观察患儿用药后的起效时间、苏醒时间、生命体征[心率、脉氧饱和度(Sp O_(2))、平均动脉压]变化以及不良反应。使用Dixon法取交叉点数据计算艾司氯胺酮ED_(50),使用概率回归法计算艾司氯胺酮ED_(50)、95%有效剂量(ED95)及其95%可信区间。组间一般资料的比较使用单因素ANOVA,组间起效时间、苏醒时间、各时间节点(静脉注射咪达唑仑后3 min、静脉注射艾司氯胺酮后3 min、手术切皮、手术结束)的生命体征(心率、Sp O_(2)、平均动脉压)的比较使用独立样本t检验;各组所需的艾司氯胺酮ED_(50)的比较使用Mann-Whitney U检验。结果·艾司氯胺酮与利多卡因联用时,行包皮环切术所需ED_(50)为1.55 mg/kg (95%CI 1.47~1.63)。与前期开展的艾司氯胺酮单药用于儿童包皮环切术的研究数据[ED_(50)=1.90 mg/kg (95%CI 1.75~2.05)]相比,两者联用时行包皮环切术所需的艾司氯胺酮ED_(50)显著降低(P=0.001),术中的平均动脉压均显著低于艾司氯胺酮单药组(P=0.000,P=0.004,P=0.010)。两药联用时对心率无明显影响,部分患儿的Sp O_(2)有一过性降低。结论·艾司氯胺酮与利多卡因联用能够显著降低儿童包皮环切术所需的艾司氯胺酮ED_(50),术中血压更平稳,但对呼吸可能存在一过性抑制。

Objective·To evaluate the median effective dose(ED_(50)) and cardiovascular stability of esketamine in combination with lidocaine for pediatric patients undergoing circumcision.Methods·Children aged 3-7 years selected for circumcision between April and June 2021 in Shanghai Children’s Medical Center,Shanghai Jiao Tong University School of Medicine were enrolled in this study.All children enrolled were administrated 0.5% lidocaine 1.5 mg/kg intravenously after anesthesia was induced by esketamine.The ED_(50)of esketamine required for children undergoing circumcision was determined by Dixon’s up-and-down method,which calculated the mean of the crossover midpoints.Additionally,ED_(50)and ED95of esketamine were estimated by probit regression.Onset time,wake-up time,vital signs including heart rate,pulse oxygen saturation and mean artery pressure,and adverse events were recorded.Differences in age,weight of the patients between the two groups were compared by one-way ANOVA.Differences in onset time,wake-up time,and vital signs including heart rate,pulse oxygen saturation(SpO_(2)) and mean arterial pressure in each time point between the two groups were compared by using the independent samples t-test.The ED_(50)values of esketamine was compared between the two groups by Mann-Whitney U test.Results·When administrated in combination with lidocaine,the ED_(50)of esketamine for children undergoing circumcision was 1.55 mg/kg(95% CI 1.47-1.63).Compared to the data of our previous study,the ED_(50)of esketamine required for children undergoing circumcision in combination with lidocaine was significantly lower than that of esketamine solo agent [ED_(50)=1.90 mg/kg(95% CI 1.75-2.05)](P=0.001).The mean arterial pressure of children pretreated with lidocaine was significantly lower than that of esketamine solo agent at each time point during the surgery(P=0.000,P=0.004,P=0.010),and no significant effect on heart rate was observed.A transient decrease in SpO_(2)was observed when esketamine was used in combination with lidocaine.Conclusion·Anesthesia induced by esketamine combined with lidocaine can significantly reduce the ED_(50)of esketamine required for pediatric patients undergoing circumcision,and better stability of blood pressure is achieved.However,transient respiratory depression should be noted.