右美托咪定对全身麻醉腹部手术后老年患者认知功能的影响

Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients with abdominal surgery

目的探讨右美托咪定对老年患者全身麻醉腹部手术后认知功能的影响,为临床预防和治疗老年患者术后认知功能障碍(POCD)提供一定的理论依据。方法选取2014年1—12月上海交通大学医学院附属仁济医院重症医学科收治的全身麻醉腹部手术后老年患者103例,随机分为右美托咪定组[52例,拔除气管导管后即予0.1μg/kg负荷量右美托咪定单次静脉给药,随后以0.3μg/(kg·h)持续静脉输注至术后48h]和对照组(51例,不使用右美托咪定)。记录两组患者术后24、48、72h的POCD发生率;分别于术前和术后2、24、48、72h各时间点,记录患者的收缩压(SBP)、心率和IL-6、皮质醇稳定蛋白(Cort)、巨噬细胞炎性蛋白-2(MIP-2)、S100钙结合蛋白(S-100β)水平;记录两组患者的术后镇痛效果和与治疗相关的不良事件发生情况。结果右美托咪定组术后24、48、72h的POCD发生率分别为5.8%(3/52)、9.6%(5/52)和1.9%(1/52),对照组分别为13.7%(7/51)、19.6%(10/51)、2.0%(1/51),右美托咪定组术后24、48h的POCD发生率均显著低于对照组同时间点(P值均<0.05),两组间术后72h的POCD发生率的差异无统计学意义(P>0.05)。右美托咪定组除了术后2h的Cort和术后72h的IL-6、Cort、MIP-2,其他术后各时间点的IL-6、Cort、MIP-2和S-100β水平均显著高于同组术前(P值均<0.05),术后72h的血清学指标基本恢复至术前水平;对照组术后各时间点的IL-6、Cort、MIP-2和S-100β水平均显著高于同组术前(P值均<0.05);除了术后2h的MIP-2,其他术后各时间点右美托咪定组的IL-6、Cort、MIP-2和S-100β水平均显著低于对照组同时间点(P值均<0.05)。右美托咪定组术后2、24、48h的SBP均显著低于同组术前和对照组同时间点(P值均<0.05),对照组组内各时间点间SBP的差异均无统计学意义(P值均>0.05);两组患者组内和组间各时间点间心率的差异均无统计学意义(P值均>0.05)。术后48h内,右美托咪定组的平均疼痛视觉模拟评分、镇痛泵按压次数和芬太尼用量均显著低于对照组(P值均<0.05)。右美托咪定组术后48h内发生低血压和窦性心动过缓各2例(3.8%),停药后恢复至术前水平;对照组术后48h内发生血压下降1例(2.0%),无窦性心动过缓发生。结论右美托咪定可以通过减轻术后应激反应和减少IL-6、Cort、MIP-2和S-100β血清释放降低老年患者全身麻醉腹部手术后的POCD发生率,且具有良好的镇痛作用,安全、有效、不良反应少,值得临床推广应用。

Objective To investigate the effect of dexmedetomidine on postoperative cognitive dysfunction （POCD） in elderly patients undergoing abdominal surgery under general anesthesia. Methods A total of 103 elderly patients undergoing abdominal surgery under general anesthesia between January and December 2014 were enrolled in this study. They were randomly divided into dexmedetomidine group （n = 52, 0. 1 μg/kg loading dose of dexmedetomidine was given and then 0.5 μg/（kg · h） of dexmedetomidine was continuously used until 48 h after operation） and control group （n = 51, no dexmedetomidine was given）. Incidences of POOD were recorded 24, 48 and 72 hours after surgery. The systolic blood pressure （SBP）, heart rate, levels of interleukin-6 （IL-6）, cortistatin （Oort）, macrophage inflammatory protein-2 （MIP-2） and S100 calcium-binding protein beta （S-10013） in serum were detected before surgery, and 2, 24, 48 and 72 hours after surgery. Postoperative analgestic effect and adverse events related to dexmedetomidine treatment were documented. Results The incidences of POOD were significantly lower 24 hours and 48 hours after surgery in dexmedetomidine group than those in control group （5.8%vs. 13.7%, 9.6% vs. 19.6%, both P《0.05）. However, there was no statistical difference in the POOD incidence in 72 hours after operation between the two groups （1.9% vs. 2.0%, P〉 0.05）. Postoperative levels of IL-6, C, ort, MIP-2 and S-100β levels were significantly higher than preoperative ones in dexmedetomidine group except for Cort at 2 hours after surgery and IL-6, Cort and MIP-2 at 72 hours after surgery （all P〈0.05）. Postoperative IL-6, Oort, MIP-2 and S-100[B levels at each time point were significantly higher than preoperative ones in control group （all P〈0.05）. The levels of IL-6, Cort, MIP-2 and S-100β in dexmedetomidine group were significantly lower than those in control group after surgery except for 2-hour postoperative MIP-2 （all P〈0. 05）. SBP in dexmedetomidine group at 2, 24, 48 hours after surgery were significantly lower than the baseline and they were also significantly lower than the those in control group （all P〈 0.05）. There were no significant differences in SBP at any time points in control group （all P〉0.05）, and no differences in heart rates at any time points were detected between the two groups （all P〉0.05）. There were lower VAS score, less demand of patient-corltrolled epidural analgesia and lower dose of fentanyl used in dexmedetomidine group than in control group 48 hours after surgery （all P〈0.05）. Two patients （3.8%） suffered from hypotension and another two with sinus bradycardia within 48 hours after operation in dexmedetomidine group, and they returned to preoperative level 48 hours after drug withdrawal. Blood pressure decreased in one patient （2.0%） within 48 hours after surgery in control group, and no sinus bradycardia occurred. Conclusion Dexmedetomidine may decrease the incidence of POCD through reducing stress response and IL-6, Cort, MIP-2, S-1001β concentrations in the elderly patients. It also has abirritation effect with less side effects. （Shanghai Med J, 2018, 41： 115-120）