右美托咪定对老年患者肝叶切除术后谵妄和早期术后认知功能障碍的预防效果

Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy

目的:术后谵妄(postoperative delirium,POD)和术后认知功能障碍(postoperative cognitive dysfunction,POCD)是围手术期常见的神经认知障碍,给患者、家庭和社会带来了沉重的负担,因此寻找合适的预防药物非常关键。既往研究证实,围手术期使用右美托咪定可降低POD和早期POCD的发生率,但在肝叶切除术老年患者中的作用及其机制尚不明确。本研究旨在观察术中使用不同剂量右美托咪定对老年肝叶切除术患者POD和早期POCD的预防效果及对促炎与抗炎失衡的影响。方法:本研究为单中心、前瞻性、随机对照试验,纳入于2019年1月至2020年12月拟择期行肝叶切除术的患者120例,年龄60~80岁,美国麻醉医师协会(American Society of Anesthesiologists,ASA)II~III级。根据随机数字表将纳入的患者分为3组(n=40):对照组(C组)、右美托咪定1组(Dex1组)和右美托咪定2组(Dex2组)。Dex1组于麻醉诱导后以0.3μg/(kg·h)的速率泵注右美托咪定;Dex2组于麻醉诱导后以0.6μg/(kg·h)的速率泵注右美托咪定;C组则泵注等体积的生理盐水。比较3组低血压和心动过缓的发生情况。于麻醉诱导前(T0)、术后第1天(T1)、术后第3天(T2)、术后第5天(T3)和术后第7天(T4),根据意识模糊评估表(Confusion Assessment Method,CAM)和简易精神状态评价量表(Mini Mental Status Examination,MMSE)评估POD及POCD的发生情况;抽取静脉血,检测神经元特异性烯醇化酶(neuron-specific enolase,NSE)、TNF-α、IL-1β及IL-10的水平。结果:Dex1组和Dex2组心动过缓发生率均明显高于C组(均P<0.05),低血压发生率与C组差异无统计学意义(均P>0.05)。C组、Dex1组和Dex2组的POD发生率分别为22.5%、5.0%和7.5%。与C组相比,Dex1组和Dex2组的POD发生率均显著降低(P<0.05)。Dex1组与Dex2组的POD发生率差异无统计学意义(P>0.05)。C组、Dex1组和Dex2组的POCD发生率分别为30.0%、12.5%和10.0%。与C组相比,Dex1和Dex2的POCD发生率均显著降低(P<0.05)。Dex1组与Dex2组的POCD发生率差异无统计学意义(P>0.05)。与C组相比,在T1~T4时间点Dex1组和Dex2组TNF-α和IL-1β显著降低,IL-10水平显著升高(均P<0.05)。与Dex1组相比,Dex2组患者T2时间点IL-1β水平、T1~T3时间点IL-10水平升高(均P<0.05)。与T0相比,C组T1~T4时间点、Dex1组和Dex2组患者T1~T3时间点的NSE水平均升高(均P<0.05)。与C组相比,Dex1组和Dex2组患者的NSE水平在T1~T4时间点均显著降低(均P<0.05)。结论:术中使用右美托咪定能降低肝叶切除术老年患者POD和POCD的发生率,其机制可能与右美托咪定下调TNF-α、IL-1β和上调IL-10水平,从而调节促炎与抗炎平衡有关。

Objective: Postoperative delirium(POD) and postoperative cognitive dysfunction(POCD)are common operative neurocognitive disorders, which places a heavy burden on patients,families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation.Methods: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020,aged 60-80 years old with American Society of Anesthesiologists(ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups(n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction,saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method(CAM) for assessing POD and Mini Mental State Examination(MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase(NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia(T0), and the first day(T1), the third day(T2), the fifth day(T3), and the seventh day(T4) after operation.Results: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased(both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group(both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group(both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group(P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%,respectively. The incidences of POCD in the Dex1 group and the Dex2 group declinedsignificantly as compared to the C group(both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group(P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points(from T1 to T4) in the Dex1 group and the Dex2 group(all P<0.05).Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group(all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points(from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased(all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group(all P<0.05).Conclusion: Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.