依达拉奉对心脏手术患者术后认知功能的影响
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摘要
背景：
术后认知障碍(postoperative cognitive dysfunction, POCD)是指手术患者在手术后出现的一系列认知功能异常。POCD不但使患者术后康复延迟,增加医疗费用,而且常与其他术后并发症伴随发生,影响其他并发症的处理与恢复,所以研究和防治POCD具有重要的临床意义。
POCD的发生机制尚不清楚,目前也没有有效的防治措施。其发生受很多因素的影响,主要包括：老年、心脏手术、糖尿病、心脑血管疾病、术后感染以及患者受教育程度较低等。心脏手术患者POCD的发生率远高于非心脏手术患者,其中短期(术后两周)认知功能改变的发生率可高达26%-61%,长期(术后1个月以上)认知功能改变的发生率也可达到5%～31%。
目前临床上诊断和研究POCD的主要手段是神经心理学测评,客观检查特异性较差,不能单独用于POCD的诊断。然而,如何规范的进行POCD的神经心理学测评目前尚无一致意见。国内大多使用一些简单的认知测评量表,缺点是项目内容过于简单,不足以全面反映患者的认知状态,因此多用于可疑患者的筛查,如用于精确的诊断和研究其可靠性值得商榷。国外对POCD的诊断研究要求更加细致,往往选择多个量表进行测评。这种测评方法的优点是可以较为细致全面的评估患者的认知功能。缺点是测评量表过多,测评过程繁琐复杂,费时较长。患者,特别是术后1周的患者,因为术后身体虚弱,能否有效的完成整个测评过程令人怀疑。而且随着使用测评量表数量的增多,POCD检出的敏感性增加,但发生第一类错误的几率也明显增加。因此,这种测评方法的可靠性同样值得商榷。
最近国内引进以色列Loewenstein康复医院设计的洛文斯顿作业疗法认知评定成套测验(Loewenstein occupational therapy cognition assessment battery, LOTCA),不但可以从定向、知觉、视运动组织和思维运作4个方面较全面的评估患者的认知功能,而且设计简单,费时约30min,似乎是较理想的POCD测评量表。但国内目前尚无临床应用的先例,其有效性仍需进一步验证。
目的：
使用LOTCA(简体中文第二版)对心脏手术患者进行术后认知功能的评估,并与简易精神状态量表(Mini-mental state examination, MMSE)进行相关性分析与比较,从而判断LOTCA能否用于POCD的临床神经心理学测评,为POCD的临床诊断和研究找寻合适的测评工具。
方法：
择期行心脏瓣膜置换手术患者30例。所有患者于术前1天和术后7天使用MMSE及LOTCA行神经心理学测评,记录相应的结果。分别计算所有患者两次测试的MMSE总分、LOTCA,总分及LOTCA七个子项目(定向、视知觉、空间知觉、动作运用、视运动组织、思维操作、注意力及专注力)共九个指标的分值。计算所有患者术前1天LOTCA,总分及LOTCA七个子项目分值的标准差,各指标术后7天测验分值与术前1天测验分值相比较,降低超过或等于1个标准差时,则诊断该指标出现功能减退；术后有2个或2个以上的指标出现功能减退则诊断该患者发生了POCD。计算MMSE总分术前1天的标准差,术后7天较术前1天降低超过或等于1个标准差时,也诊断该患者发生了POCD。所得数据采用SPSS11.0统计学软件进行统计学分析。分析比较二者对POCD的诊断率、MMSE和LOTCA评分及检测时间的差异。组间比较采用成组t检验,计数资料比较采用卡方检验。九个指标采用Spearman相关性检验做相关性分析。P<0.05为差异有统计学意义。
结果：
1.患者采用MMSE测评诊断POCD13例(43.33%),采用LOTCA测评诊断POCD17例(56.67%)。诊断率比较差异无统计学意义(x2=1.067,P=0.302)。
2.患者MMSE总分与LOTCA总分呈正相关关系(γ=0.711,P=0.005)。
3.术后7天的MMSE总分和LOTCA,总分较术前1天明显降低,差异有统计学意义。LOTCA七个子项目中,动作运用、视运动组织、思维操作、注意力及专注力四个子项目得分亦有明显降低,差异有统计学意义。
4. MMSE测评时间术前1天为9.902±3.619min,术后7天为12.27±5.137min,两者差异有统计学意义(P<0.05)。LOTCA测评时间术前1天为28.25±8.778min,术后7天为36.27±11.26min。两者差异有统计学意义(P<0.01)。
结论：
1.本研究认为,LOTCA可用于POCD的诊断与评估,与国内外常用的神经心理学测评方法相比,LOTCA既保证了对患者认知功能的全面评估,又使整个测评过程简洁紧凑,是更为理想的神经心理学测评手段。
2. LOTCA七个子项目中,动作运用、视运动组织、思维操作、注意力及专注力四个子项目得分术后7天较术前1天明显降低,似乎表明越复杂的认知功能术后减退的程度越大。
3. LOTCA术后7天的测评时间较术前1天明显延长,而且术后7天患者注意力及专注力得分明显降低,这可能与患者术后身体虚弱有关。
4.与MMSE相比,LOTCA的测评时间仍然较长,部分患者术后因身体虚弱需分两次完成测评。但是,与国外使用多个量表进行测评相比,LOTCA的测评时间仍在患者可以接受的程度之内。
背景：
心脏手术患者是POCD发生的高危人群。然而,目前人们仍不清楚这一现象发生的原因是什么。既往人们认为体外循环过程可能在其中发挥了重要的作用。但是,进一步的研究却并不支持这样的看法。最近的研究认为POCD的发生可能与全身炎性反应以及体外循环期间复温过程中脑组织复温不均衡有关,但也有很多相反的观点,具体原因仍有待进一步的研究。
对心脏手术患者而言,POCD的发生无疑将严重影响患者术后的病情恢复。这不仅意味着患者康复时间延长,医疗费用增加,而且有资料显示,POCD可能与患者术后感染、心脑血管意外等多种并发症互为因果。因此,采取措施减少和预防POCD的发生具有重要的医学、社会和经济意义。
虽然有很多研究意图寻找预防和减少心脏手术患者POCD发生几率的办法,然而迄今为止我们仍没有找到有效的方法来解决这一问题。依达拉奉(edaravone)是一种氧自由基清除剂,主要用于神经系统疾病。有研究表明,依达拉奉可以明显改善脑血管疾病患者和脑外伤患者的认知功能。因此,本实验希望研究依达拉奉能否改善心脏手术患者术后的认知功能,能否预防和减少POCD的发生率。
目的：
研究依达拉奉对心脏手术患者术后认知功能的影响,探讨其能否改善心脏手术患者术后的认知功能。
方法：
选择济南军区总医院医院心外科自2011年3月至2011年8月行心脏瓣膜置换术患者60例,随机分为两组,即依达拉奉组(Edaravone Group,E组)和对照组(Control Group,C组),每组30例。分组过程按照双盲原则由专人负责,试验药物由分组人员配制。其中依达拉奉注射液1.0mg·kg-1稀释成100ml用于E组患者,生理盐水100ml用于C组患者。实验人员分别在麻醉诱导后30分钟内和体外循环开始后30分钟内使用微量泵各泵入试验药物50ml。所有患者分别于麻醉诱导前(T1)、手术结束时(T2)、术后1小时(T3)、术后6小时(T4)、术后24小时(T5)采集桡动脉血3ml,采集的血样保存于-20℃冰箱,择期采用免疫夹心双抗体酶联免疫吸附法(ELISA)定量检测患者血清中IL-6、TNF-α, Aβ1-40含量。
所有患者分别于术前1天、术后7天和术后3个月使用LOTCA行神经心理学测评,并记录相应的结果。分别计算所有患者在各时间段的LOTCA总分及LOTCA七个子项目(定向、视知觉、空间知觉、动作运用、视运动组织、思维操作、注意力及专注力)的分值。计算所有患者术前1天LOTCA,总分及LOTCA七个子项目分值的标准差,各指标术后7天或术后3个月测验分值与术前1天测验分值相比较,降低超过或等于1个标准差时,则诊断该指标在该时间段出现功能减退；术后7天或术后3个月有2个或2个以上的指标出现功能减退则诊断该患者发生了POCD。
应用统计软件SPSS11.0进行统计学处理。组间比较采用t检验,计数资料比较采用卡方检验(Fisher's exact test)以P<0.05为差异有统计学意义。
结果：
1.两组患者一般情况比较差异无统计学意义。
2. POCD诊断率的比较：术后7天,C组有1例患者死亡,E组有2例患者因病情危重失访(29例vs28例)；C组与E组之间POCD诊断率差异无统计学意义(13例vs11例,P=0.601)。术后3个月,C组再有2例患者失访(因某些原因拒绝测试),E组再有3例患者失访(其中1例患者死亡,2例患者因某些原因拒绝测试)(27例vs25例)；C组与E组之间POCD诊断率差异无统计学意义(6例vs5例,P=0.732)。
3.血清中IL-6、TNF-α、Aβ1-40含量的比较：血清中IL-6、TNF-α含量在Tl、T2时间点两组之间差异无统计学意义。但在T3、T4、T5三个时间点E组含量要低于C组含量,两组之间差异有统计学意义。A β1-40含量在T1、T2、T3、T4、T5时间点两组之间差异无统计学意义。
结论：
1.术中使用依达拉奉是不能改善心脏瓣膜手术患者术后认知功能的。
2.术中使用依达拉奉对患者血清Aβ1-40的含量没有明显影响,从而辅助说明了其对心脏瓣膜手术患者术后认知功能是没有明显的作用的。
3.术中使用依达拉奉可以减少患者血清中炎性因子的含量,可以减少患者术后全身炎性反应。但全身炎性反应的减轻并不能改善患者术后的认知功能。说明POCD的发生机制十分复杂,使用炎性因子作为能否改善患者术后认知状况的指标是不可取的。
Background
Postoperative cognitive dysfunction (POCD) refers to a functional decrease in cognition, personality and social activities after anesthesia and surgery with clinical manifestations of dysfunction in memory, attention, orientation, language, thinking as well as social behavior. POCD not only make the delay of postoperative rehabilitation and increase costs of health care, but also have other complications associated with treatment and recovery. So researches the prevention of POCD have important clinical benefit.
The mechanism of POCD is still unclear:there is no effective prevention measure too. It is affected by a lot of factors, mainly including:the elderly, heart surgery, diabetes, cerebrovascular disease, postoperative infection and the lower education degree. The incidence of POCD is far higher in cardiac surgery patients. At short-term (two weeks) after surgery, the rates of cognitive dysfunction as high as26%～61%, and long-term (one month) the incidence also has5%～31%.
At present, the clinical diagnosis of POCD is mainly by neuropsychological test. Specificity of other examination is poor and can not be used for POCD diagnosis. However, how to carry out neuropsychological test is disagreement. In China, we mostly used some simple cognitive assessment scale; the disadvantage is the project contents are too simple, and not enough to reflect the cognitive status of patients. So the results are debatable. In foreign, the diagnosis of POCD is requiring more meticulous and often chooses many scales. This method is more meticulous and overall evaluation cognitive functions. But the defect is the process of assessment complex, and the time-consuming too long. Patients, especially one week after operation, whether can finish the whole assessment process is suspect due to the weak body. And. with the increase of assessment scale, sensitivity of checkout POCD is increasing, but the first kind of error is increasing obviously too. Therefore, the reliability of this method is also questionable.
Loewenstein occupational therapy cognition assessment battery (LOTCA) is not only for comprehensive evaluation of patients with cognitive function, but also design simple. Time consuming is about30minute. It seems to be the ideal assessment scale of POCD. But there is no clinical application at present:its validity will require further validation.
Objective
To investigate the clinical efficiency of LOTCA (Simplified Chinese Version, the2nd Edition) on the evaluation of POCD in patients went through cardiac valve replacement. In addition, a correlation analysis with LOTCA and MMSE was performed. So we judge whether LOTCA can use for clinical neuropsychological test for POCD. This study provides an appropriate assessment tools for the evaluation of POCD.
Methods
Thirty patients with no mental disorder and/or organ dysfunction went through cardiac valve replacement were included in this study. MMSE and LOTCA were performed1d before the surgery and7d after the surgery. The MMSE testing score, LOTCA testing score and its corresponding subprojects including orientation, visual and spatial perception, executive functions, visual motor organization, thinking and attention were determined, respectively. A comparative study was performed between the testing scores obtained on the7d after surgery and1d before the surgery. For the LOTCA analysis, hypofunction was designated in the presence of a decrease of one or more standard deviation. POCD was designated provided that≥2items showed decrease. For the MMSE analysis, patients were diagnosed with POCD provided that a decrease of standard deviation≤1. SPSS11.0Software was used for the statistical analysis. A Student's t test was used for the inter-group comparison. Chi square test was used for the numeration data. Spearman rank correlation analysis was performed for the correlation among all the indices. P<0.05demonstrated significant statistical difference.
Results
1. Among the30patients,13(43.3%) were diagnosed with POCD with MMSE while17(56.7%) were diagnosed with POCD with LOTCA. No statistical difference was noted (χ2=1.067, P=0.302).
2. A strong correlation was detected between the test scores of MMSE and LOTCA (y=0.711, P<0.01). In addition, the correlation among MMSE, LOTCA and its corresponding subprojects were also investigated.
3. Significant decrease of the test scores of MMSE, LOTCA. Four of its seven aspects including executive functions, visual motor organization, thinking and attention was noted on the7d after surgery compared with these obtained Id before the surgery (P<0.05).
4. Compared with the scores obtained1d before the surgery, significant difference was noted between the MMSE testing time on the7d after surgery (12.27±5.137min vs9.902±3.619min, P<0.05). For the LOTCA analysis, significant difference was noted between the testing time on the7d after surgery compared with those obtained1d before the surgery (36.27±11.26min vs28.25±8.778min, P<0.01).
Conclusion
1. This study suggested that LOTCA applicable for POCD diagnosis and evaluation. Compared with other methods, LOTCA not only effective assessed the cognitive function in patients, but also the assessment provided a concise process. LOTCA was a more ideal neuropsychological assessment method.
2. For the seven subjects during LOTCA. the major functional decrease was noted in Motor Praxis, Visuomotor Organization, Thinking Operations, Attention and Concentration on7d after surgery compared with those obtained on Id before surgery. It seemed to indicate the more complex abstracts of cognitive function maybe greater decline.
3. The testing time on the7d after surgery was significantly longer than1d before the surgery maybe related to the weak of patients.
4. The time of assessment with LOTCA is still longer than MMSE; some patients should complete assessment in twice because of weak. But compared with using multiple scale in foreign, the time of assessment with LOTCA is still acceptable.
Background
POCD in heart surgery patients was happening at higher risk. However, we still didn't know the reason of it. We always think that cardiopulmonary bypass (CPB) process was playing an important role. However, further research didn't support this view. Recent studies suggested that POCD maybe caused by systemic inflammatory response syndrome and unbalance of brain temperature in rewarming process during CPB. But there were many opposite views too. The reason of it remained to be further research.
POCD not only delayed postoperative rehabilitation and increased the costs of health care, but also had other complications associated with treatment and recovery. So the researches of prevented POCD have important clinical benefits.
While there were many researches tried to look for a way to decrease the risk of POCD in heart surgery patients, but we still didn't find effective ways to solve the problem. Edaravone is a kind of oxygen free radical scavenger, mainly used on the patients of nervous system disease. A large number of researches indicated that edaravone could significantly improve cognitive function in cerebrovascular disease and brain injury patients. Therefore, this study hopes to research whether edaravone can improve postoperative cognitive function and reduce the incidence of POCD in heart surgery patients.
Objective
Researched the influence of postoperative cognitive function by edaravone for heart surgery patients, and discussed whether it can improve postoperative cognitive function and reduce the incidence of POCD in heart surgery patients.
Methods
Sixty patients scheduled for elective heart valve replacement were recruited to participate in this clinical trial from March2011to Augest2011,randomly divided into two groups, namely Edaravone Group(E Group) and Control Group (C Group), each group had30patients. According to the principle of double blind, the grouping process was by a specially-assigned person, the test drugs prepared by the specially-assigned person too. In E Group, edaravone (1.0mg·kg-1) diluted into100ml with normal saline, and otherwise normal saline100ml used for patients in C Group. Researcher pumped50ml test drug in30minutes after the induction of anaesthesia and the begining of CPB respectively. All of patients were collected3ml radial artery blood at Before induction (T1). End of surgery (T2),1hour after surgery (T3),6hours after surgery (T4) and24hours after surgery (T5). The blood samples stored in the refrigerator at-20℃. the serum content of1L-6, TNF-α, Aβ1-40was detected by immune sandwich double antibody elisa method.
All of patients were tested with LOTCA in1day preoperation.7days postoperation and3months postoperation. and record the corresponding results. Recorded total score of LOTCA and scores of seven subprojects (Orientation, Visual Perception, Spatial Perception, Motor Praxis, Visuomotor Organization, Thinking Operations and attention and concentration) of all patients in every times. Calculated standard deviation of the1day preoperation of LOTCA total score and seven subprojects scores, the scores of7days or3months postoperation reduced equal or than one standard deviation were diagnosed impairment in this time period, and two or more impairment were diagnosed POCD.
SPSS11.0was use to statistical analysis. Measurement date compared with t-test and count date compared with chi-square test (Fisher's exact test). Statistical significance was set at P<0.05.
Results
1. No significant difference was noted of the patients' general situation between two groups.
2. Compare with diagnostic rate of POCD:At7days postoperation, one patient died in C group and two patients were lost in E group (29vs28), the diagnostic rate of POCD was no significant difference between two groups (13vs11, P=0.601). At3months postoperation,2patients lost once more(refused testing) in C group and3patients lost once more (one died and two refused testing) in E group (27vs25), the diagnostic rate of POCD was no significant difference between two groups (6vs5, P=0.732)
3. Compared the contents of IL-6, TNF-α, Aβ1-40in serum:The contents of IL-6and TNF-a were no significant differences at T1and T2between two groups. But at T3. T4and T5, E group were lower than C group, the differences between two groups had statistically significant. The contents of Aβ1-40were no significant differences between two groups at T1, T2, T3,T4and T5.
Conclusion
1. Edaravone used intraoperative can not improve the postoperation cognitive function in cardiac valvular surgery patients.
2. The contents of Aβ1-40were no significant differences between two groups also showed that edaravone was no obvious effect in improving the postoperation cognitive function in cardiac valvular surgery patients.
3. Edaravone used intraoperative can reduce the serum levels of inflammatory factors. it can reduce the postoperative systemic inflammatory response syndrome. But the reduction of systemic inflammatory response syndrome did not improve the cognitive function after surgery. It showed that mechanism of POCD was very complex. Inflammatory factors were not indicators to assess cognitive status of patients.
术后认知障碍(postoperative cognitive dysfunction, POCD)是指手术患者在手术后出现的一系列认知功能异常。POCD不但使患者术后康复延迟,增加医疗费用,而且常与其他术后并发症伴随发生,影响其他并发症的处理与恢复,所以研究和防治POCD具有重要的临床意义。
POCD的发生机制尚不清楚,目前也没有有效的防治措施。其发生受很多因素的影响,主要包括：老年、心脏手术、糖尿病、心脑血管疾病、术后感染以及患者受教育程度较低等。心脏手术患者POCD的发生率远高于非心脏手术患者,其中短期(术后两周)认知功能改变的发生率可高达26%-61%,长期(术后1个月以上)认知功能改变的发生率也可达到5%～31%。
目前临床上诊断和研究POCD的主要手段是神经心理学测评,客观检查特异性较差,不能单独用于POCD的诊断。然而,如何规范的进行POCD的神经心理学测评目前尚无一致意见。国内大多使用一些简单的认知测评量表,缺点是项目内容过于简单,不足以全面反映患者的认知状态,因此多用于可疑患者的筛查,如用于精确的诊断和研究其可靠性值得商榷。国外对POCD的诊断研究要求更加细致,往往选择多个量表进行测评。这种测评方法的优点是可以较为细致全面的评估患者的认知功能。缺点是测评量表过多,测评过程繁琐复杂,费时较长。患者,特别是术后1周的患者,因为术后身体虚弱,能否有效的完成整个测评过程令人怀疑。而且随着使用测评量表数量的增多,POCD检出的敏感性增加,但发生第一类错误的几率也明显增加。因此,这种测评方法的可靠性同样值得商榷。
最近国内引进以色列Loewenstein康复医院设计的洛文斯顿作业疗法认知评定成套测验(Loewenstein occupational therapy cognition assessment battery, LOTCA),不但可以从定向、知觉、视运动组织和思维运作4个方面较全面的评估患者的认知功能,而且设计简单,费时约30min,似乎是较理想的POCD测评量表。但国内目前尚无临床应用的先例,其有效性仍需进一步验证。
目的：
使用LOTCA(简体中文第二版)对心脏手术患者进行术后认知功能的评估,并与简易精神状态量表(Mini-mental state examination, MMSE)进行相关性分析与比较,从而判断LOTCA能否用于POCD的临床神经心理学测评,为POCD的临床诊断和研究找寻合适的测评工具。
方法：
择期行心脏瓣膜置换手术患者30例。所有患者于术前1天和术后7天使用MMSE及LOTCA行神经心理学测评,记录相应的结果。分别计算所有患者两次测试的MMSE总分、LOTCA,总分及LOTCA七个子项目(定向、视知觉、空间知觉、动作运用、视运动组织、思维操作、注意力及专注力)共九个指标的分值。计算所有患者术前1天LOTCA,总分及LOTCA七个子项目分值的标准差,各指标术后7天测验分值与术前1天测验分值相比较,降低超过或等于1个标准差时,则诊断该指标出现功能减退；术后有2个或2个以上的指标出现功能减退则诊断该患者发生了POCD。计算MMSE总分术前1天的标准差,术后7天较术前1天降低超过或等于1个标准差时,也诊断该患者发生了POCD。所得数据采用SPSS11.0统计学软件进行统计学分析。分析比较二者对POCD的诊断率、MMSE和LOTCA评分及检测时间的差异。组间比较采用成组t检验,计数资料比较采用卡方检验。九个指标采用Spearman相关性检验做相关性分析。P<0.05为差异有统计学意义。
结果：
1.患者采用MMSE测评诊断POCD13例(43.33%),采用LOTCA测评诊断POCD17例(56.67%)。诊断率比较差异无统计学意义(x2=1.067,P=0.302)。
2.患者MMSE总分与LOTCA总分呈正相关关系(γ=0.711,P=0.005)。
3.术后7天的MMSE总分和LOTCA,总分较术前1天明显降低,差异有统计学意义。LOTCA七个子项目中,动作运用、视运动组织、思维操作、注意力及专注力四个子项目得分亦有明显降低,差异有统计学意义。
4. MMSE测评时间术前1天为9.902±3.619min,术后7天为12.27±5.137min,两者差异有统计学意义(P<0.05)。LOTCA测评时间术前1天为28.25±8.778min,术后7天为36.27±11.26min。两者差异有统计学意义(P<0.01)。
结论：
1.本研究认为,LOTCA可用于POCD的诊断与评估,与国内外常用的神经心理学测评方法相比,LOTCA既保证了对患者认知功能的全面评估,又使整个测评过程简洁紧凑,是更为理想的神经心理学测评手段。
2. LOTCA七个子项目中,动作运用、视运动组织、思维操作、注意力及专注力四个子项目得分术后7天较术前1天明显降低,似乎表明越复杂的认知功能术后减退的程度越大。
3. LOTCA术后7天的测评时间较术前1天明显延长,而且术后7天患者注意力及专注力得分明显降低,这可能与患者术后身体虚弱有关。
4.与MMSE相比,LOTCA的测评时间仍然较长,部分患者术后因身体虚弱需分两次完成测评。但是,与国外使用多个量表进行测评相比,LOTCA的测评时间仍在患者可以接受的程度之内。
背景：
心脏手术患者是POCD发生的高危人群。然而,目前人们仍不清楚这一现象发生的原因是什么。既往人们认为体外循环过程可能在其中发挥了重要的作用。但是,进一步的研究却并不支持这样的看法。最近的研究认为POCD的发生可能与全身炎性反应以及体外循环期间复温过程中脑组织复温不均衡有关,但也有很多相反的观点,具体原因仍有待进一步的研究。
对心脏手术患者而言,POCD的发生无疑将严重影响患者术后的病情恢复。这不仅意味着患者康复时间延长,医疗费用增加,而且有资料显示,POCD可能与患者术后感染、心脑血管意外等多种并发症互为因果。因此,采取措施减少和预防POCD的发生具有重要的医学、社会和经济意义。
虽然有很多研究意图寻找预防和减少心脏手术患者POCD发生几率的办法,然而迄今为止我们仍没有找到有效的方法来解决这一问题。依达拉奉(edaravone)是一种氧自由基清除剂,主要用于神经系统疾病。有研究表明,依达拉奉可以明显改善脑血管疾病患者和脑外伤患者的认知功能。因此,本实验希望研究依达拉奉能否改善心脏手术患者术后的认知功能,能否预防和减少POCD的发生率。
目的：
研究依达拉奉对心脏手术患者术后认知功能的影响,探讨其能否改善心脏手术患者术后的认知功能。
方法：
选择济南军区总医院医院心外科自2011年3月至2011年8月行心脏瓣膜置换术患者60例,随机分为两组,即依达拉奉组(Edaravone Group,E组)和对照组(Control Group,C组),每组30例。分组过程按照双盲原则由专人负责,试验药物由分组人员配制。其中依达拉奉注射液1.0mg·kg-1稀释成100ml用于E组患者,生理盐水100ml用于C组患者。实验人员分别在麻醉诱导后30分钟内和体外循环开始后30分钟内使用微量泵各泵入试验药物50ml。所有患者分别于麻醉诱导前(T1)、手术结束时(T2)、术后1小时(T3)、术后6小时(T4)、术后24小时(T5)采集桡动脉血3ml,采集的血样保存于-20℃冰箱,择期采用免疫夹心双抗体酶联免疫吸附法(ELISA)定量检测患者血清中IL-6、TNF-α, Aβ1-40含量。
所有患者分别于术前1天、术后7天和术后3个月使用LOTCA行神经心理学测评,并记录相应的结果。分别计算所有患者在各时间段的LOTCA总分及LOTCA七个子项目(定向、视知觉、空间知觉、动作运用、视运动组织、思维操作、注意力及专注力)的分值。计算所有患者术前1天LOTCA,总分及LOTCA七个子项目分值的标准差,各指标术后7天或术后3个月测验分值与术前1天测验分值相比较,降低超过或等于1个标准差时,则诊断该指标在该时间段出现功能减退；术后7天或术后3个月有2个或2个以上的指标出现功能减退则诊断该患者发生了POCD。
应用统计软件SPSS11.0进行统计学处理。组间比较采用t检验,计数资料比较采用卡方检验(Fisher's exact test)以P<0.05为差异有统计学意义。
结果：
1.两组患者一般情况比较差异无统计学意义。
2. POCD诊断率的比较：术后7天,C组有1例患者死亡,E组有2例患者因病情危重失访(29例vs28例)；C组与E组之间POCD诊断率差异无统计学意义(13例vs11例,P=0.601)。术后3个月,C组再有2例患者失访(因某些原因拒绝测试),E组再有3例患者失访(其中1例患者死亡,2例患者因某些原因拒绝测试)(27例vs25例)；C组与E组之间POCD诊断率差异无统计学意义(6例vs5例,P=0.732)。
3.血清中IL-6、TNF-α、Aβ1-40含量的比较：血清中IL-6、TNF-α含量在Tl、T2时间点两组之间差异无统计学意义。但在T3、T4、T5三个时间点E组含量要低于C组含量,两组之间差异有统计学意义。A β1-40含量在T1、T2、T3、T4、T5时间点两组之间差异无统计学意义。
结论：
1.术中使用依达拉奉是不能改善心脏瓣膜手术患者术后认知功能的。
2.术中使用依达拉奉对患者血清Aβ1-40的含量没有明显影响,从而辅助说明了其对心脏瓣膜手术患者术后认知功能是没有明显的作用的。
3.术中使用依达拉奉可以减少患者血清中炎性因子的含量,可以减少患者术后全身炎性反应。但全身炎性反应的减轻并不能改善患者术后的认知功能。说明POCD的发生机制十分复杂,使用炎性因子作为能否改善患者术后认知状况的指标是不可取的。
Background
Postoperative cognitive dysfunction (POCD) refers to a functional decrease in cognition, personality and social activities after anesthesia and surgery with clinical manifestations of dysfunction in memory, attention, orientation, language, thinking as well as social behavior. POCD not only make the delay of postoperative rehabilitation and increase costs of health care, but also have other complications associated with treatment and recovery. So researches the prevention of POCD have important clinical benefit.
The mechanism of POCD is still unclear:there is no effective prevention measure too. It is affected by a lot of factors, mainly including:the elderly, heart surgery, diabetes, cerebrovascular disease, postoperative infection and the lower education degree. The incidence of POCD is far higher in cardiac surgery patients. At short-term (two weeks) after surgery, the rates of cognitive dysfunction as high as26%～61%, and long-term (one month) the incidence also has5%～31%.
At present, the clinical diagnosis of POCD is mainly by neuropsychological test. Specificity of other examination is poor and can not be used for POCD diagnosis. However, how to carry out neuropsychological test is disagreement. In China, we mostly used some simple cognitive assessment scale; the disadvantage is the project contents are too simple, and not enough to reflect the cognitive status of patients. So the results are debatable. In foreign, the diagnosis of POCD is requiring more meticulous and often chooses many scales. This method is more meticulous and overall evaluation cognitive functions. But the defect is the process of assessment complex, and the time-consuming too long. Patients, especially one week after operation, whether can finish the whole assessment process is suspect due to the weak body. And. with the increase of assessment scale, sensitivity of checkout POCD is increasing, but the first kind of error is increasing obviously too. Therefore, the reliability of this method is also questionable.
Loewenstein occupational therapy cognition assessment battery (LOTCA) is not only for comprehensive evaluation of patients with cognitive function, but also design simple. Time consuming is about30minute. It seems to be the ideal assessment scale of POCD. But there is no clinical application at present:its validity will require further validation.
Objective
To investigate the clinical efficiency of LOTCA (Simplified Chinese Version, the2nd Edition) on the evaluation of POCD in patients went through cardiac valve replacement. In addition, a correlation analysis with LOTCA and MMSE was performed. So we judge whether LOTCA can use for clinical neuropsychological test for POCD. This study provides an appropriate assessment tools for the evaluation of POCD.
Methods
Thirty patients with no mental disorder and/or organ dysfunction went through cardiac valve replacement were included in this study. MMSE and LOTCA were performed1d before the surgery and7d after the surgery. The MMSE testing score, LOTCA testing score and its corresponding subprojects including orientation, visual and spatial perception, executive functions, visual motor organization, thinking and attention were determined, respectively. A comparative study was performed between the testing scores obtained on the7d after surgery and1d before the surgery. For the LOTCA analysis, hypofunction was designated in the presence of a decrease of one or more standard deviation. POCD was designated provided that≥2items showed decrease. For the MMSE analysis, patients were diagnosed with POCD provided that a decrease of standard deviation≤1. SPSS11.0Software was used for the statistical analysis. A Student's t test was used for the inter-group comparison. Chi square test was used for the numeration data. Spearman rank correlation analysis was performed for the correlation among all the indices. P<0.05demonstrated significant statistical difference.
Results
1. Among the30patients,13(43.3%) were diagnosed with POCD with MMSE while17(56.7%) were diagnosed with POCD with LOTCA. No statistical difference was noted (χ2=1.067, P=0.302).
2. A strong correlation was detected between the test scores of MMSE and LOTCA (y=0.711, P<0.01). In addition, the correlation among MMSE, LOTCA and its corresponding subprojects were also investigated.
3. Significant decrease of the test scores of MMSE, LOTCA. Four of its seven aspects including executive functions, visual motor organization, thinking and attention was noted on the7d after surgery compared with these obtained Id before the surgery (P<0.05).
4. Compared with the scores obtained1d before the surgery, significant difference was noted between the MMSE testing time on the7d after surgery (12.27±5.137min vs9.902±3.619min, P<0.05). For the LOTCA analysis, significant difference was noted between the testing time on the7d after surgery compared with those obtained1d before the surgery (36.27±11.26min vs28.25±8.778min, P<0.01).
Conclusion
1. This study suggested that LOTCA applicable for POCD diagnosis and evaluation. Compared with other methods, LOTCA not only effective assessed the cognitive function in patients, but also the assessment provided a concise process. LOTCA was a more ideal neuropsychological assessment method.
2. For the seven subjects during LOTCA. the major functional decrease was noted in Motor Praxis, Visuomotor Organization, Thinking Operations, Attention and Concentration on7d after surgery compared with those obtained on Id before surgery. It seemed to indicate the more complex abstracts of cognitive function maybe greater decline.
3. The testing time on the7d after surgery was significantly longer than1d before the surgery maybe related to the weak of patients.
4. The time of assessment with LOTCA is still longer than MMSE; some patients should complete assessment in twice because of weak. But compared with using multiple scale in foreign, the time of assessment with LOTCA is still acceptable.
Background
POCD in heart surgery patients was happening at higher risk. However, we still didn't know the reason of it. We always think that cardiopulmonary bypass (CPB) process was playing an important role. However, further research didn't support this view. Recent studies suggested that POCD maybe caused by systemic inflammatory response syndrome and unbalance of brain temperature in rewarming process during CPB. But there were many opposite views too. The reason of it remained to be further research.
POCD not only delayed postoperative rehabilitation and increased the costs of health care, but also had other complications associated with treatment and recovery. So the researches of prevented POCD have important clinical benefits.
While there were many researches tried to look for a way to decrease the risk of POCD in heart surgery patients, but we still didn't find effective ways to solve the problem. Edaravone is a kind of oxygen free radical scavenger, mainly used on the patients of nervous system disease. A large number of researches indicated that edaravone could significantly improve cognitive function in cerebrovascular disease and brain injury patients. Therefore, this study hopes to research whether edaravone can improve postoperative cognitive function and reduce the incidence of POCD in heart surgery patients.
Objective
Researched the influence of postoperative cognitive function by edaravone for heart surgery patients, and discussed whether it can improve postoperative cognitive function and reduce the incidence of POCD in heart surgery patients.
Methods
Sixty patients scheduled for elective heart valve replacement were recruited to participate in this clinical trial from March2011to Augest2011,randomly divided into two groups, namely Edaravone Group(E Group) and Control Group (C Group), each group had30patients. According to the principle of double blind, the grouping process was by a specially-assigned person, the test drugs prepared by the specially-assigned person too. In E Group, edaravone (1.0mg·kg-1) diluted into100ml with normal saline, and otherwise normal saline100ml used for patients in C Group. Researcher pumped50ml test drug in30minutes after the induction of anaesthesia and the begining of CPB respectively. All of patients were collected3ml radial artery blood at Before induction (T1). End of surgery (T2),1hour after surgery (T3),6hours after surgery (T4) and24hours after surgery (T5). The blood samples stored in the refrigerator at-20℃. the serum content of1L-6, TNF-α, Aβ1-40was detected by immune sandwich double antibody elisa method.
All of patients were tested with LOTCA in1day preoperation.7days postoperation and3months postoperation. and record the corresponding results. Recorded total score of LOTCA and scores of seven subprojects (Orientation, Visual Perception, Spatial Perception, Motor Praxis, Visuomotor Organization, Thinking Operations and attention and concentration) of all patients in every times. Calculated standard deviation of the1day preoperation of LOTCA total score and seven subprojects scores, the scores of7days or3months postoperation reduced equal or than one standard deviation were diagnosed impairment in this time period, and two or more impairment were diagnosed POCD.
SPSS11.0was use to statistical analysis. Measurement date compared with t-test and count date compared with chi-square test (Fisher's exact test). Statistical significance was set at P<0.05.
Results
1. No significant difference was noted of the patients' general situation between two groups.
2. Compare with diagnostic rate of POCD:At7days postoperation, one patient died in C group and two patients were lost in E group (29vs28), the diagnostic rate of POCD was no significant difference between two groups (13vs11, P=0.601). At3months postoperation,2patients lost once more(refused testing) in C group and3patients lost once more (one died and two refused testing) in E group (27vs25), the diagnostic rate of POCD was no significant difference between two groups (6vs5, P=0.732)
3. Compared the contents of IL-6, TNF-α, Aβ1-40in serum:The contents of IL-6and TNF-a were no significant differences at T1and T2between two groups. But at T3. T4and T5, E group were lower than C group, the differences between two groups had statistically significant. The contents of Aβ1-40were no significant differences between two groups at T1, T2, T3,T4and T5.
Conclusion
1. Edaravone used intraoperative can not improve the postoperation cognitive function in cardiac valvular surgery patients.
2. The contents of Aβ1-40were no significant differences between two groups also showed that edaravone was no obvious effect in improving the postoperation cognitive function in cardiac valvular surgery patients.
3. Edaravone used intraoperative can reduce the serum levels of inflammatory factors. it can reduce the postoperative systemic inflammatory response syndrome. But the reduction of systemic inflammatory response syndrome did not improve the cognitive function after surgery. It showed that mechanism of POCD was very complex. Inflammatory factors were not indicators to assess cognitive status of patients.
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19. Moiler JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCDI study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction[J]. Lancet,1998,351(9106):857-61.
20. Steinmetz J, Christensen KB, Lund T, et al. Long-term Consequences of Postoperative Cognitive Dysfunction [J]. Anesthesiology,2009,110: 548-55.
21. Annes G, Katz N, Cermak SA. Comparison of younger and older healthy adults on the Loewenstein Occupational Therapy. Cognitive Assessment Occupational Therapy International,1996,3:57—173.
22.燕铁斌,伍少玲,郭友华,等Loewenstein认知评定量表与简易精神状态检查评定脑损伤患者认知功能的比较[J].中华物理医学与康复杂志,2004,26(7)：400-403.
1、Newman MF, Kirchner JL, Phillips-Bute B, etal. Longitudinal assessment of neurocognitive after coronary artery bypass surgery[J]. N Engl J Med,2001,344:395—402.
2、Kadoi Y, Goto F. Factors associated with postoperative cognitive dysfunction in patients undergoing cardiac surgery[J]. Surg Tody, 2006,36:1053—1057.
3、Rolfson DB, McElhaney JE, Rockwood K, et al. Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery[J]. Can J Cardiol,1999, 15:771-776.
4、Hornick P, Smith PL, Taylor KM, et al. Cerebral complications after coronary bypass grafting. Curr Opin Cardiol,1994,9:670-679.
5、Ying-Hua Liu, Dong-Xin Wang, Li-Huan Li, et al. The effects of cardiopulmonary bypass on the number of cerebral microemboli and the incidence of cognitive dysfunction after coronary artery bypass graft surgery [J]. Anesth Analg,2009,109:1013-22.
6、Hanne A, Peter H, Bjorn S,et al. Cerebral blood flow and cognitive dysfunction after coronary surgery[J]. Ann Thorac Surg,2002,73: 1174-78.
7、Wan Y, Xu J, Ma D, et al. Postoperative impairment of cognitive function in rats:a possible role for cytokine-mediated inflammation in the hippocampus[J]. Anesthesiology,2007; 106(3):43643.
8、Gunstad J,Bausserman L, Paul RH, et al. C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease [J]. J Clin Neurosei,2006,13(5):317-26.
9、Howard JN, George AW, Janet LM, et al. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass:a randomized trial[J]. circulation,2001, 104:85-91.
10、Westaby S, Saatvedt K, White S, et al. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass[J]?Ann Thorac Surg,2001; 71(2):667-72.
11、Bettina J, Barbara E, Manfred B, et al. The impact of cardiopulmonary bypass on systemic interleukin-6 release, cerebral nuclear factor-kappa B expression, and neurocognitive outcome in rats [J]. Anesth Analg,2010,110:312-20.
12、Mitchell SJ, Merry AF, Frampton C, et al. Cerebral protection by lidocaine during cardiac operations:a follow-up study. Ann Thorac Surg 2009; 87:820-825.
13、蔡志友,晏勇,张骏,等.依达拉奉对血管性认知功能损害大鼠IL-1β、 TNF-α与VEGF表达的影响.重庆医科大学学报2009,34(1)：66-70.
14、Kreuer S, Biedler A, Larsen R, et al. The NarcotrendTM-a new EEG monitor designed to measure the depth of anaesthesia[J]. Anaesthesist,2001,50(12):921-925.
15、Ray PG, Meador KJ, Loring DW, et al. Central anticholinergic hypersensitivity in aging [J]. J Geriatr Psychiatry Neurol,1992, 5(2):72-77.
16、Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Peri operative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996,335:1857-1863.
17、Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid β42 and amyloid β40 levels are associated with early cognitive dysfunction after cardiac surgery[J]. Ann Thorac Surg,2009,88:1426-32.
18、Vannini P, Almkvist 0, Dierks T, et al. Reduced neuronal efficacy in progressive mild cognitive impairment:a prospective fMRI study on visuospatial processing[J]. Psychiatry Res,2007,156(1):43-57.
19、Engelhardt W, Dierks T, Pause M, et al. P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass graft ing[J]. Eur J Cardiothorac Surg,1995,9: 12-17.
20、Planel E, Richter KE, Nolan CE, et al. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia[J]. J Neurosci,2007,27(12):3090-7.
21、Traykov L, Rigaud AS, Baudic S, et al. Apolipoprotein E epsilon 4 allele frequency in demented and cognitively impaired patients with and without cerebrovascular disease [J]. J Neurol Sci 2002,203: 177-81.
22、Silbert BS, Evered LA, Scott DA, et al. The apolipoprotein Eε 4 allele is not associated with cognitive dysfunction in cardiac surgery[J]. Ann Thorac Surg 2008,86:841-8.
1. Ronald C, Rachelle Doody, Alexander Kurz, et al. Current concepts in mild cognitive impairment[J]. Arch Neurol,2001,58:1985-1992.
2. Moiler JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCDI study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction[J]. Lancet,1998,351(9106):857-61.
3.曹建国,洪涛,闻大翔,等.老年患者术后精神和认知障碍的发病率及相关因素分析[J].上海医学,2005；28(11)：93941.
4.倪东妹,时听,吴新民.老年病人全麻术后认知功能障碍的发病率[J].中国麻醉与镇痛,2004；6(3)：164-6.
5. Selnes OA, Grega MA, Borowicz LM Jr, et al. Cognitive changes with coronary artery disease:a prospective study of coronary artery bypass graft patients and nonsurgical controls[J]. Ann Thorac Surg,2003,75:1377-1384; discussion 1384-1386.
6.疏树华,潘建辉,方才,等.老年非心脏手术患者全身麻醉术后认知功能障碍的发生率及影响因素[J].中国临床保健杂志,2009,12(2)：128-130.
7. Newman MF, Kirchner JL, Phillips-Bute B, etal. Longitudinal assessment of neurocognitive after coronary artery bypass surgery [J]. N Engl J Med,2001,344:395—402.
8. Kadoi Y, Goto F. Factors associated with postoperative cognitive dysfunction in patients undergoing cardiac surgery [J]. Surg Tody, 2006,36:1053—1057.
9. Rolfson DB, McElhaney JE, Rockwood K, et al. Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery[J]. Can J Cardiol, 1999,15:771-776.
10. Hornick P, Smith PL, Taylor KM, et al. Cerebral complications after coronary bypass grafting. Curr Opin Cardiol,1994,9:670-679.
11. Ying-Hua Liu, Dong-Xin Wang, Li-Huan Li, et al. The effects of cardiopulmonary bypass on the number of cerebral microemboli and the incidence of cognitive dysfunction after coronary artery bypass graft surgery [J]. Anesth Analg,2009,109:1013-22.
12. Hanne A, Peter H, Bjorn S, et al. Cerebral blood flow and cognitive dysfunction after coronary surgery[J].Ann Thorac Surg,2002,73:1174-78.
13. Wan Y, Xu J, Ma D, et al. Postoperative impairment of cognitive function in rats:a possible role for cytokine-mediated inflammation in the hippocampus[J]. Anesthesiology,2007; 106(3): 43643.
14. Gunstad J, Bausserman L, Paul RH, et al. C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease[J]. J Clin Neurosei,2006,13(5): 317-26.
15. Howard JN, George AW, Janet LM, et al. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass:a randomized trial[J]. circulation,2001,104:85-91.
16. Westaby S, Saatvedt K, White S, et al. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass[J]?Ann Thorac Surg,2001; 71(2):667-72.
17. Bettina J, Barbara E, Manfred B, et al. The impact of cardiopulmonary bypass on systemic interleukin-6 release, cerebral nuclear factor-kappa B expression, and neurocognitive outcome in rats[J].Anesth Analg,2010,110:312-20.
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22. Belanoff JK, Gross K,Yager A,et al. Corticosteroids and cognition[J]. J Psychiatr Res,2001,35(3):127-45.
23. Heffelfinger AK, Newcomer JW. Glucocorticoid effects on memory function over the human life span[J]. Dev Psychopathol,2001,13(3):491-513.
24. Lupien SJ, Nair NP, Briere S, et al. Increased cortisol levels and impaired cognition in human aging:implication for depression and dementia in later life[J]. Rev Neurosci,1999,10:117-39.
25. Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid β 42 and amyloid β 40 levels are associated with early cognitive dysfunction after cardiac surgery[J]. Ann Thorac Surg,2009,88:1426-32.
26. Annes G, Katz N, Cermak SA. Comparison of younger and older healthy adults on the Loewenstein Occupational Therapy[J]. Cognitive Assessment Occupational Therapy International,1996,3(3):57— 173.
27.郁可,范建中,李树雯.第2版Loewenstein认知评定量表的临床应用[J].中国康复,2005,20(3)：147-8.
28.张善纲,范建中,郁可,等.洛文斯顿作业疗法认知评定量表中文应用软件的研制[J].中国康复理论与实践,2006,12(4)：287-9.
29. Jack CR Jr, Petersen RC, Xu Y, et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD[J]. Neuroloy,2000,55(4):484-489.
30. Vannini P, Almkvist O, Dierks T, et al. Reduced neuronal efficacy in progressive mild cognitive impairment:a prospective fMRI study on visuospatial processing[J]. Psychiatry Res,2007,156(1):43-57.
31. W Engelhardt, T Dierks, M Pause, et al. P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass grafting[J]. Eur J Cardiothorac Surg,1995,9:12-17.
32. Planel E, Richter KE, Nolan CE, et al. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia[J]. J Neurosci,2007,27(12):3090-7.
33.李曙光.轻度认知障碍和老年性痴呆关系的研究[J].安徽医学,2002,23(5)：34-35.
34. Xie Z, Dong Y, Maeda U, et al. Isoflurane-induced apoptosis:a potential pathogenic link between delirium and dementia[J]. J Gerontol A Biol Sci Med Sci,2006,61(12):1300-6.
35. Lisbeth A. Evered, BS, MBiostata, et al. Plasma amyloid β 42 and amyloid β 40 levels are associated with early cognitive dysfunction after cardiac surgery [J]. Ann Thorac Surg,2009,88: 1426-1432.
36. Farag E, Chelune GJ, Schubert A, et al. Is depth of anesthesia, as assessed by the bispectral index, related to postoperative cognitive dysfunction and recovery [J]? Anesth Analg,2006,103: 633-40.
37. Wong J, Song D, Blanshard H, et al. Titration of isoflurane using BIS index improves early recovery of elderly patients undergoing orthopedic surgeries [J]. Can J Anaesth,2002,49:13-18.
38. Gaba VK, Mathews DM, Zhaku B, et al. Correlation of the intraoperative bispectral index score (BIS) with incidence of postoperative cognitive disorders (POCD) in the geriatric population [J]. Anesth Analg,2004,98:S-71.
39. Fellery L, Wilbert LJ, George BM, et al.The effect of limited rewarming and postoperative hypothermia on cognitive function in a rat cardiopulmonary bypass model [J]. Anesth Analg,2008,106 (3): 739-45.
40. Munir B, Fraser DR, Denise W, et al. Predictors of early neurocognitive deficits in low-risk patients undergoing on-pump coronary artery bypass surgery[J]. Circulation,2006,114:1-461-6.
41. Howard JN, George AW, Janet LM, et al. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass:a randomized trial[J]. Circulation, 2001,104:85-91.
42.赵红,张丽.认知护理对老年患者全身麻醉术后认知障碍的影响[J].齐鲁护理杂志,2005,11(1)：16-17.
43.李丽萍,江晓,葛衡江.术后疼痛对老年患者术后早期认知功能的影响[J].重庆医学,2009,38(14)：1802-4.
44. Matthew SL, Paul M, Brendan SS, et al. Detection of postoperative cognitive decline after coronary artery bypass graft surgery is affected by the number of neuropsychological tests in the assessment battery[J]. Ann Thorac Surg,2006,81:2097-2104.
45. Matthew SL,BAppSc Hons, Paul TM, et al. Examination of the Use of Cognitive Domains in Postoperative Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery[J]. Ann Thorac Surg,2005, 80:910-916.
46. Silbert BS, Maruff P, Evered LA, et al.Detection of cognitive decline after coronary surgery:a comparison of computerized and conventional tests [J]. Br J Anaesth,2004,92(6):814-20.
47.鹿洪秀,苏帆.载脂蛋白Ee4等位基因与高龄患者术后认知功能障碍关系的研究[J].新医学,2009,40(8)：512-4.
48. Tardiff BE, Newman MF, Saunders AM, et al. Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center [J]. Ann Thorac Surg,1997,64 (3):715-720
49. Brendan SS, Lisbeth AE, David AS, et al. The apolipoprotein Eε 4 allele is not associated with cognitive dysfunction in cardiac surgery[J]. Ann Thorac Surg,2008,86:841-8.
50. Iohom G, Szarvas S, Larney V, et al. Perioperative plasma concentrations of stable nitric oxide products are predictive of cognitive dysfunction after laparoscopic cholecystectomy [J]. Anesth Analg,2004,99:1245-52.
51.罗红.术后1CU患者精神障碍相关因素的分析[J].中国现代医学杂志,2003,13(15)：30-31.
52.李源,李晓苗,陶国才,等.老年术后认知功能障碍与血压节律及胰岛素抵抗的相关性[J].中华老年多器官疾病杂志,2009,8(5)：402-404.
53.李丽萍,江晓,葛衡江.术后疼痛对老年患者术后早期认知功能的影响[J]. 重庆医学,2009,38(14)：1802-1804.
54. Ramlawi B, Rudolph JL, Mieno S, et al. C-reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery[J]. Surgery,2006,140:221-226.
55.周懿之,陈杰,王祥瑞,等.不停跳冠状动脉搭桥术患者术后认知功能障碍及与C-反应蛋白的关系[J].临床麻醉学杂志,2009,25(6)：465-7.
56.李显华,张传汉,姚文龙,等.不同统计学指标评价体外循环心内直视术后患者早期认知功能障碍的比较[J].中华麻醉学杂志,2007,27(2)：156-159.
2. Kadoi Y, Goto F. Factors associated with postoperative cognitive dysfunction in patients undergoing cardiac surgery[J]. Surg Tody, 2006,36:1053—1057.
3. Vannini P, Almkvist 0, Dierks T, et al. Reduced neuronal efficacy in progressive mild cognitive impairment:a prospective fMRI study on visuospatial processing[J]. Psychiatry Res,2007,156(1):43-57.
4. Engelhardt W, Dierks T, Pause M, et al. P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass grafting[J]. Eur J Cardiothorac Surg,1995, 9:12-17.
5. Planel E, Richter KE, Nolan CE, et al. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia[J]. J Neurosci,2007,27(12):3090-7.
6. Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid β42 and amyloid β40 levels are associated with early cognitive dysfunction after cardiac surgery [J]. Ann Thorac Surg,2009,88(7):1426-1432.
7. Nathan HJ, Wells GA, Munson JL, et al. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass:a randomized trial [J]. circulation,2001,104: 85-91.
8. Lewis MS. Maruff P, Silbert BS, et al. Detection of postoperative cognitive decline after coronary artery bypass graft surgery is affected by the number of neuropsychological tests in the assessment battery[J]. Ann Thorac Surg,2006,81:2097-2104.
9. Lewis MS. Maruff PT, Silbert BS, et al. Examination of the Use of Cognitive Domains in Postoperative Cognitive Dysfunction After Coronary Artery Bypass Graft Surgery[J]. Ann Thorac Surg,2005,80:910-916.
10.燕铁斌,马超,郭友华,等.Loewenstein认知评定量表(简体中文版)的效度及信度研究[J].中华物理医学与康复杂志,2004,26(2)：81-84.
11.郁可,范建中,李树雯.第2版Loewenstein认知评定量表的临床应用[J].中国康复,2005,20(3)：147-148.
12. Kreuer S, Biedler A, Larsen R, et al. The NarcotrendTM-a new EEG monitor designed to measure the depth of anaesthesia[J]. Anaesthesist, 2001,50(12):921-925.
13. Ray PG, Meador KJ, Loring DW, et al. Central anticholinergic hypersensitivity in aging [J]. J Geriatr Psychiatry Neurol,1992,5(2): 72-77.
14. Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid β 42 and amyloid β40 levels are associated with early cognitive dysfunction after cardiac surgery [J]. Ann Thorac Surg,2009,88:1426-32.
15. Belanoff JK, Gross K,Yager A, et al. Corticosteroids and cognition[J]. J Psychiatr Res,2001,35(3):127-45.
16. Heffelfinger AK, Newcomer JW. Glucocorticoid effects on memory function over the human life span[J]. Dev Psychopathol,2001, 13(3):491-513.
17. Ramlawi B, Rudolph JL, Mieno S, et al. C-reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery[J]. Surgery,2006,140:221-226.
18.周懿之,陈杰,王祥瑞,等.不停跳冠状动脉搭桥术患者术后认知功能障碍及与C-反应蛋白的关系[J].临床麻醉学杂志,2009,25(6)：465-7.
19. Moiler JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCDI study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction[J]. Lancet,1998,351(9106):857-61.
20. Steinmetz J, Christensen KB, Lund T, et al. Long-term Consequences of Postoperative Cognitive Dysfunction [J]. Anesthesiology,2009,110: 548-55.
21. Annes G, Katz N, Cermak SA. Comparison of younger and older healthy adults on the Loewenstein Occupational Therapy. Cognitive Assessment Occupational Therapy International,1996,3:57—173.
22.燕铁斌,伍少玲,郭友华,等Loewenstein认知评定量表与简易精神状态检查评定脑损伤患者认知功能的比较[J].中华物理医学与康复杂志,2004,26(7)：400-403.
1、Newman MF, Kirchner JL, Phillips-Bute B, etal. Longitudinal assessment of neurocognitive after coronary artery bypass surgery[J]. N Engl J Med,2001,344:395—402.
2、Kadoi Y, Goto F. Factors associated with postoperative cognitive dysfunction in patients undergoing cardiac surgery[J]. Surg Tody, 2006,36:1053—1057.
3、Rolfson DB, McElhaney JE, Rockwood K, et al. Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery[J]. Can J Cardiol,1999, 15:771-776.
4、Hornick P, Smith PL, Taylor KM, et al. Cerebral complications after coronary bypass grafting. Curr Opin Cardiol,1994,9:670-679.
5、Ying-Hua Liu, Dong-Xin Wang, Li-Huan Li, et al. The effects of cardiopulmonary bypass on the number of cerebral microemboli and the incidence of cognitive dysfunction after coronary artery bypass graft surgery [J]. Anesth Analg,2009,109:1013-22.
6、Hanne A, Peter H, Bjorn S,et al. Cerebral blood flow and cognitive dysfunction after coronary surgery[J]. Ann Thorac Surg,2002,73: 1174-78.
7、Wan Y, Xu J, Ma D, et al. Postoperative impairment of cognitive function in rats:a possible role for cytokine-mediated inflammation in the hippocampus[J]. Anesthesiology,2007; 106(3):43643.
8、Gunstad J,Bausserman L, Paul RH, et al. C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease [J]. J Clin Neurosei,2006,13(5):317-26.
9、Howard JN, George AW, Janet LM, et al. Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass:a randomized trial[J]. circulation,2001, 104:85-91.
10、Westaby S, Saatvedt K, White S, et al. Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass[J]?Ann Thorac Surg,2001; 71(2):667-72.
11、Bettina J, Barbara E, Manfred B, et al. The impact of cardiopulmonary bypass on systemic interleukin-6 release, cerebral nuclear factor-kappa B expression, and neurocognitive outcome in rats [J]. Anesth Analg,2010,110:312-20.
12、Mitchell SJ, Merry AF, Frampton C, et al. Cerebral protection by lidocaine during cardiac operations:a follow-up study. Ann Thorac Surg 2009; 87:820-825.
13、蔡志友,晏勇,张骏,等.依达拉奉对血管性认知功能损害大鼠IL-1β、 TNF-α与VEGF表达的影响.重庆医科大学学报2009,34(1)：66-70.
14、Kreuer S, Biedler A, Larsen R, et al. The NarcotrendTM-a new EEG monitor designed to measure the depth of anaesthesia[J]. Anaesthesist,2001,50(12):921-925.
15、Ray PG, Meador KJ, Loring DW, et al. Central anticholinergic hypersensitivity in aging [J]. J Geriatr Psychiatry Neurol,1992, 5(2):72-77.
16、Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Peri operative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996,335:1857-1863.
17、Evered LA, Silbert BS, Scott DA, et al. Plasma amyloid β42 and amyloid β40 levels are associated with early cognitive dysfunction after cardiac surgery[J]. Ann Thorac Surg,2009,88:1426-32.
18、Vannini P, Almkvist 0, Dierks T, et al. Reduced neuronal efficacy in progressive mild cognitive impairment:a prospective fMRI study on visuospatial processing[J]. Psychiatry Res,2007,156(1):43-57.
19、Engelhardt W, Dierks T, Pause M, et al. P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass graft ing[J]. Eur J Cardiothorac Surg,1995,9: 12-17.
20、Planel E, Richter KE, Nolan CE, et al. Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia[J]. J Neurosci,2007,27(12):3090-7.
21、Traykov L, Rigaud AS, Baudic S, et al. Apolipoprotein E epsilon 4 allele frequency in demented and cognitively impaired patients with and without cerebrovascular disease [J]. J Neurol Sci 2002,203: 177-81.
22、Silbert BS, Evered LA, Scott DA, et al. The apolipoprotein Eε 4 allele is not associated with cognitive dysfunction in cardiac surgery[J]. Ann Thorac Surg 2008,86:841-8.
1. Ronald C, Rachelle Doody, Alexander Kurz, et al. Current concepts in mild cognitive impairment[J]. Arch Neurol,2001,58:1985-1992.
2. Moiler JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCDI study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction[J]. Lancet,1998,351(9106):857-61.
3.曹建国,洪涛,闻大翔,等.老年患者术后精神和认知障碍的发病率及相关因素分析[J].上海医学,2005；28(11)：93941.
4.倪东妹,时听,吴新民.老年病人全麻术后认知功能障碍的发病率[J].中国麻醉与镇痛,2004；6(3)：164-6.
5. Selnes OA, Grega MA, Borowicz LM Jr, et al. Cognitive changes with coronary artery disease:a prospective study of coronary artery bypass graft patients and nonsurgical controls[J]. Ann Thorac Surg,2003,75:1377-1384; discussion 1384-1386.
6.疏树华,潘建辉,方才,等.老年非心脏手术患者全身麻醉术后认知功能障碍的发生率及影响因素[J].中国临床保健杂志,2009,12(2)：128-130.
7. Newman MF, Kirchner JL, Phillips-Bute B, etal. Longitudinal assessment of neurocognitive after coronary artery bypass surgery [J]. N Engl J Med,2001,344:395—402.
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