Effect of dexmedetomidine on postoperative cognitive dysfunction in patients after cardiac surgery with cardiopulmonary bypass

目的 观察右美托咪定(DEX)对体外循环(CPB)心脏手术患者围手术期中枢炎症反应的影响,进而探讨其对该类患者术后认知功能障碍(POCD)发生的影响. 方法 将自2013年7月至2014年6月在浙江省人民医院心胸外科行择期CPB心脏手术患者80例,采用随机数字表法均分为对照组和DEX组,每组40例.DEX组患者麻醉诱导前给予DEX 1 μg/kg,然后以0.5 μg/(kg,h)速度持续输注至手术结束;对照组患者在同时段给予等量生理盐水.分别于麻醉诱导后切皮前(T0)、CPB开始后30 min(T1)、CPB停止后30 min(T2)、手术结束时(T3)、手术结束后24 h(T4)及手术结束后72 h(TS)等6个时间点从颈静脉球部采集血液标本检测肿瘤坏死因子α(TNF-α)、白介素-6(IL-6)及白介素-10(IL-10)水平;分别于术前1d及术后3、7、90、180d采用简易智能精神状态检测量表(MMSE)及数字广度(DSpan,顺向和逆向)、数字符号(DSy)、循环连线(TMT)测试量表评估患者的认知功能. 结果 (1)在T1、T2、T3时间点,2组患者血浆TNF-α、IL-6及IL-10水平均明显高于组内T0时间点,差异均有统计学意义(P＜0.05);DEX组TNF-α及IL-6水平均明显低于同时间点对照组,差异均有统计学意义(P＜0.05);DEX组IL-10水平均明显高于同时间点对照组,差异均有统计学意义(P＜0.05).(2)对照组术后3d除TMT外的所有量表结果,及术后7 d MMSE、DSpan-逆向评分,以及术后90 d DSpan-逆向评分均明显低于术前1d,差异均有统计学意义(P＜0.05);DEX组术后3 d MMSE、DSpan-逆向评分均明显低于术前1d,差异均有统计学意义(P＜0.05).DEX组术后3d及7 d MMSE、DSpan-逆向评分,以及术后90 d DSpan-逆向评分均明显高于对照组,差异均有统计学意义(P＜0.05);DEX组术后3 dTMT时间明显低于对照组,差异有统计学意义(氏0.05).(3)DEX组术后3、7dPOCD发生率(23.5％、14.7％)均明显低于对照组(46.9％、37.5％),差异均有统计学意义(P＜0.05). 结论 在麻醉诱导前给予DEX 1 μg/kg负荷及术中0.5 μg/(kg·h)维持,可在一定程度上抑制CPB心脏手术患者中枢炎症反应,从而改善术后认知功能,进而减少早期POCD的发生,但不能减少长期POCD的发生.Objective To evaluate the effect of dexmedetomidine (DEX) on inflammatory responses in patients performed cardiac surgery with cardiopulmonary bypass (CPB) at perioperative period,and explore the influencing factors of postoperative cognitive dysfunction (POCD) in these patients.Methods Eighty patients scheduled for cardiac surgery with CPB at hospital from July 2013 to June 2014 were randomized into control group and DEX group (n=40).Before induction of anesthesia,DEX was administered to the patients from DEX group with a loading dose of 1 μg/kg followed by maintenance dose of 0.5 μg/ (kg·h),while the same dose of normal saline was administered to patients from control group.Before incision (T0),30 min after beginning of CBP (T1),30 min after end of CBP (T2),end of surgery (T3),24 h after end of surgery (T4) and 72 h after end of surgery (T5),venous blood samples from jugular bulb catheters were drawn,and serum concentrations of tumor necrosis factor α (TNF-αt),interleukin (IL)-6 and IL-10 were determined.One d before operation,3nd,7th,90th and 180th day after operation,the cognitive functions of patients were tested with mini-mental state examination (MMSE),digit span subtest (DSpan),digit symbol subtest (DSy) and trail making test (TMT).The DSpan contained digit span forward subtest (DSpan-F) and digit span reverse subtest (DSpan-R).Results The serum concentrations of TNF-α,IL-6 and IL-10 in two groups at T1,T2 and T3 were significantly higher than those at T0 (P＜0.05);the serum concentrations of TNF-α and IL-6 in DEX group were significantly lower than those in control group (P＜0.05),while that of IL-10 in DEX group was significantly higher than that in control group (P＜0.05).In the control group,all results excepted for TMT on the 3nd d after operation,MMSE and DSpan-R results on the 7th d after operation,and DSpan-R results on the 90th d after operation were significantly lower than those results one d before operation (P＜0.05);in the DEX group,MMSE and DSpan-R results on the 3nd d after operation were significantly lower than those results one d before operation (P＜0.05);MMSE and DSpan-R results on the 3nd and 7th d after operation,and DSpan-R results on the 90th d after operation in the DEX group were significantly higher than those in the control group (P＜0.05);TMT on the 3nd after operation in the DEX group was significantly lower than that in the control group (P＜0.05).The incidence rate of POCD in the DEX group on the 3nd and 7th d after operation (23.5％ and 14.7％) was significantly lower than that in the control group (46.9％ and 37.5％,P＜0.05).Conclusion DEX with a loading dose of 1 iμg/kg followed by maintenance dose of 0.5 μg/ (kg· h) can reduce the early incidence of POCD in cardiac surgery with cardiopulmonary bypass,but can not reduce the late incidence.浙江省自然科学基金; 浙江省医学会临床科研基金; Natural Science Foundation of Zhejiang Province; Clinical Scientific Research Foundation of Zhejiang Province Medical Association中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)4391-3961