目的 观察诱导前静注亚剂量艾司氯胺酮（esketamine，ESKE）复合咪达唑仑（midazolam， MI）对老年髋关节置换术后谵妄（post operative delirium，POD）的影响，探讨 ESKE 复合 MI 对谷氨酸（gluta⁃ mate，G）诱导 HT22 细胞损伤的作用。方法 髋关节置换术 65 岁以上患者 120 例，随机均分为 C 组、MI 组、ESKE 组和 ESKE+MI 组。诱导前 10 min MI 组静注 0.02 mg/kg MI、ESKE 组给 0.2 mg/kg ESKE、ESKE+MI 组给 0.2 mg/kg ESKE 和 0.02 mg/kg MI 混合液、C 组给等量生理盐水，观察术后 72 h 内 POD 发生率；将 HT22 细胞分为NC、G、MIC、ESKEC和ESKEC+MIC组，各组按相应设计处理后行CCK⁃8检测，流式法测凋亡率和坏 死率。结果 4组一般资料及血流动力学比较差异无统计学意义（P < 0.05），ESKE+MI组POD发生率低于C 组，POD 组血清 G 高于 NPOD 组（P < 0.05）；NC 与 G 组比较 OD 值、坏死率和凋亡率比较差异有统计学意义 （P < 0.05）；ESKEC和ESKEC+MIC组OD值高于G组（P < 0.05）；ESKEC和ESKEC+MIC组坏死率和凋亡率低于 G 组（P < 0.05）。结论 亚剂量 ESKE 复合 MI 麻醉前给药可降低髋关节置换老年患者 POD 发生率；ESKE 复合MI 可减轻G 引起的HT22细胞凋亡和坏死，ESKE 复合MI 降低患者POD 发生率可能与此机制相关。

Objective To observe the effect of intravenous injections of sub ⁃ dose esketamine combined with midazolam before anesthesia induction on postoperative delirium （POD）in elderly patients receiving hip replacement. To explore the role of ESKE combined with MI in glutamate ⁃ induced HT22 cell injury. Methods 120 patients older than 65 who had undergone hip replacement were randomly assigned to group C，MI，ESKE or ESKE plus MI，30 for each group. 10 minutes before anesthesia，group MI received intravenous midazolam of 0.02 mg/kg，group ESKE received esketamine of 0.2 mg/kg，group ESKE plus MI received esketamine combined with midazolam，while group C received saline. The incidence of POD within 72 hours was observed. HT22 cells were divided into groups NC，G，MIC，ESKEC and ESKEC plus MIC. CCK8 was detected in each group following treatments based on relevant design. Rates of apoptosis and necrosis were measured by flow cytometry. Results The general data and hemodynamic index in the patients were not statistically significant（P > 0.05）. The inci⁃ dence of POD was lower in group ESKE plus MI than in group C，while glutamate level was higher in group POD than in group NPOD（P < 0.05）. The OD value and rates of necrosis and apoptosis in group NC，as compared with group C，were statistically significant（P < 0.05）. The OD value was greater in groups ESKEC and ESKEC plus MIC than in group G（P < 0.05）. The rates of apoptosis and necrosis were higher in group G than in groups ESKEC and ESKEC plus MIC（P < 0.05）. Conclusions Uses of sub ⁃dose esketamine combined with midazolam before anesthesia can reduce the incidence of POD in elderly patients undergoing hip replacement. ESKE combined with MI can relieve the apoptosis and necrosis of HT22 cells induced by glutamate，whose mechanism may be related to the decline in the incidence of POD.