【指南共识】成人术后谵妄防治的专家共识（2020版）

万小健（共同执笔人），王东信（共同执笔人/共同负责人），方向明（共同负责人），邓小明（共同负责人），江来，宋青，张西京，张鸿飞，周建新，思永玉，袁世荧，皋源，诸杜明，徐桂萍，康焰， 穆东亮

谵妄是一种急性发作且病程短暂的脑功能障碍，其特点是注意力障碍、意识水平紊乱和认知功能改变，并有明显的波动性¹。术后谵妄（postoperative delirium，POD）是指患者在经历外科手术后1周内出现的谵妄，其发生具有明显的时间特点，主要发生在术后24h～72h以内²。由于谵妄患者多表现为嗜睡、沉默不语等的“低活动型”症状，常为临床忽视^3-5。在ICU中约35%的谵妄患者被漏诊或误诊⁶，多数患者没有得到足够的重视与相应的处理或治疗。但术后谵妄的发生伴随患者预后不良^7-9。基于此，中华医学会麻醉学分会组织专家，系统收集相关文献，在2014版专家共识的基础上制定本专家共识，以提高大家对术后谵妄的重视。 

一、术后谵妄流行病学和危害

术后谵妄的发病率因患者人群、手术类型、手术时机（急诊或择期）、谵妄评估工具，甚至病房在医院内位置等因素而异。不同报告的发生率差异很大，如心脏手术后谵妄发生率为6%~46%¹⁰，血管手术后为5%~39%¹¹，胃肠道手术后为8%~54%¹²，关节置换手术后为5%~14%¹³。

一般而言，谵妄常见于老年患者，特别是手术前已有神经、精神合并症的老年患者¹⁴。术后谵妄发生率也与手术类型有关，通常小手术和日间手术后谵妄的发生率较低，大手术后发生率较高。如白内障手术后约为4.4%，耳鼻喉科手术后约12%，普外科手术后约13%，神经外科术后约21.4%，大动脉手术后约29%，而腹部大手术和心脏手术后分别高达50%和51%^15-25。另外，有创手术术后谵妄发生率高于介入手术，急诊手术高于择期手术^17,20。

术后谵妄对患者早期和远期预后都有不良影响。研究显示谵妄患者术后并发症发生风险增加2~3倍、围术期死亡风险增加2~3倍，且住院时间延长和住院期间医疗费用增加^15-25。长期随访研究结果显示谵妄患者术后远期认知功能障碍发生率增加、生活质量降低、远期死亡率增加^10,26,27。

【推荐意见】谵妄是外科术后常见并发症，多见于老年患者、大手术后，其发生常伴随患者预后不良。建议对医护人员进行培训以提高对谵妄的认识。

二、术后谵妄的危险因素

术后谵妄是多种因素共同作用的结果，可分为易感因素（表1）和促发因素（表2）。谵妄的发生是易感人群在促发因素诱导下出现的结果。了解这些因素有助于识别术后谵妄的高危人群，以便采取相应的预防措施。

表1. 术后谵妄的易感因素

表2. 术后谵妄的促发因素

（一）常见的易感因素

1. 老年  高龄是术后谵妄的易感因素。65岁以上患者谵妄发生率明显增加，且随年龄增长而增加²⁸。 

2．认知功能损害或储备减少  术前存在认知功能改变（如痴呆、认知功能损害、抑郁等）的患者易于发生术后谵妄^29-31。某些与精神或认知功能异常相关的基因可能与谵妄风险增加相关（如SLC6A3基因、DRD2基因、COMT基因和NMDA受体基因）^32-34。术前对认知功能状况进行筛查有助于发现术后谵妄的高危患者。

3.生理功能储备减少  术前存在自主活动受限、活动耐量降低或存在视觉、听觉损害的老年患者，术后易发生谵妄^35,36。术前衰弱的老年患者，无论心脏手术还是非心脏手术，术后谵妄风险均增加^37,38。

4.摄入减少  术前存在脱水、电解质紊乱、严重低蛋白血症及维生素D缺乏等的患者术后易发生谵妄^39-41。

5.并存疾病  既往脑卒中史是术后谵妄的独立危险因素⁴²，且术后脑卒中也伴随术后谵妄风险增加⁴³；隐匿性脑卒中的患者，术后谵妄风险也增加2.24倍⁴⁴。创伤和骨折患者多病情紧急，术后谵妄发生率高于其他择期手术患者⁴⁵。术前合并睡眠紊乱的患者术后谵妄发生风险增加5.24倍⁴⁶。HIV感染患者也是谵妄的高发人群，发生率约30%~57%⁴⁷。病情严重时多个器官系统受累或存在代谢紊乱（如酸碱失衡、电解质紊乱、高血糖等），均可导致术后谵妄风险增加^48,49。

6. 药物  术前应用影响精神活动的药物以及酗酒均可增加术后谵妄风险^49-51。术前应用药物品种过多，预示发生术后谵妄的风险增加。

（二）常见的促发因素

    1．药物  苯二氮卓类药物（如劳拉西泮、地西泮、咪达唑仑等）可增加谵妄发生风险。抗胆碱能药物（如戊乙奎醚、东莨菪碱、阿托品、格隆溴铵等）可引起谵妄和认知功能损害，老年患者尤其敏感，可能与其通过血脑屏障阻断中枢M受体有关。常用抗胆碱能药物的血脑屏障通过率：格隆溴铵<阿托品<东莨菪碱<戊乙奎醚。因此，围手术期使用抗胆碱能药物时应尽可能选择透过血脑屏障少的药物，如格隆溴铵和阿托品^52,53。

2．手术种类  术后谵妄在心血管手术和矫形外科手术后较为多见，非心脏大手术和高危手术后也较多见，而小手术后发生率较低^15-18,54。长时间体外循环可增加术后谵妄的发生⁵⁵。

3.  ICU环境  ICU是谵妄的高发病区，除了ICU患者多为高龄、高危患者外，可能与ICU的特殊环境有关⁵⁶。

4.  术中因素  研究显示术中麻醉深度与术后谵妄具有相关性，双频指数（BIS）指导的麻醉深度管理可降低术后谵妄的发生率⁵⁷。低脑氧饱和度也是术后谵妄的危险因素之一^58,59。低血压或血压高于脑血流自身调节范围也可能导致谵妄风险增加，但目前结论尚不统一^12,60,61，但术中血压波动较大被认为是术后谵妄的预测因素⁶²。此外，体温过低或过高均可影响神经功能，导致谵妄、意识混乱甚至昏迷的发生⁶³。

5.  术后并发症  术后并发症可增加谵妄发生的风险。并发症越多越重，发生谵妄的风险越大^26,64,65。

6.  术后睡眠障碍  睡眠障碍是术后常见并发症，可表现为睡眠剥夺、睡眠破碎、睡眠节律紊乱、睡眠结构紊乱等，睡眠障碍可导致谵妄风险增加^46,66。

【推荐意见】谵妄是在多种危险因素共同作用下发生的脑功能障碍。关注谵妄危险因素有助于尽早识别高危患者，及时给予预防和干预措施。

三、 临床表现

谵妄发作的特点是急性起病、病程波动，症状多在24h内出现、消失或加重、减轻，常有中间清醒期。术后谵妄最主要特点是注意力障碍、意识水平紊乱和认知功能障碍，但可有多种临床表现。

1. 注意力障碍  表现为患者对各种刺激的警觉性及指向性下降，例如注意力难唤起，表情茫然，不能集中注意力，同时注意力保持、分配和转移也可能有障碍。

2. 意识水平紊乱  表现为对周围环境认识的清晰度下降（尤其是缺乏外界环境刺激时）或者出现不同程度的木僵或昏迷。

3. 广泛的认知功能障碍 为术后谵妄最常见的表现之一，其主要症状如下：

（1）知觉障碍  主要表现为知觉的鉴别和整合能力下降，常表现为各种形式的错觉和幻觉，以幻觉居多。乙醇或镇静药物戒断引起的谵妄表现为警觉性、活动性增高，而代谢性（肝性、肾性）障碍引起的谵妄表现为警觉性、活动性降低。

（2）思维障碍  主要表现为思维结构解体及言语功能障碍。思维连贯性、推理与判断能力下降，有时伴有不完整、不系统、松散的类偏执症状。

（3）记忆障碍  记忆全过程中各个方面都可有障碍，包括识记、保持、记忆、再认、再现。

4. 睡眠-觉醒周期障碍  典型表现为白天昏昏欲睡，夜间失眠，间断睡眠，或完全的睡眠周期颠倒。

5. 神经运动异常  高活动型表现为警觉、激动，易出现幻觉、错觉及激越行为；低活动型表现为嗜睡，运动活动明显减少；混合型患者则可交替出现高活动型和低活动型症状。

6. 情绪失控  主要表现为间断出现恐惧、妄想、焦虑、抑郁、躁动、淡漠、愤怒、欣快等，且症状不稳定有波动。

谵妄的临床表现有两个明显的特征：①起病急；②病程波动：症状常在24h内出现、消失或加重、减轻，常有中间清醒期。

术后谵妄可分为三种类型，高活动型、低活动型和混合型。其中高活动型谵妄约占25%，患者有明显的烦躁不安、易激惹、突发攻击、幻觉和胡言乱语等症状，一般易为护士或家属关注。低活动型谵妄约占50%，患者主要症状为嗜睡、沉默不语、安静不动和认知分离，常为临床忽视。混合型谵妄约占25%左右，兼有高活动型和低活动型谵妄的部分临床特点^3-5。

【推荐意见】谵妄以注意力障碍、意识水平紊乱、认知功能障碍为主要临床表现，有起病急、病程波动的特点。谵妄常表现为低活动型，漏诊和误诊率较高。

四、诊断与鉴别诊断

（一）诊断

精神障碍诊断与统计手册第五版（Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition，DSM-V）诊断标准是谵妄诊断的金标准⁶⁷。但DSM-V诊断标准适合精神专业人员应用，未经专门训练的非精神专业人员不容易掌握。目前临床常用且适合非精神专业人员使用的谵妄诊断工具主要包括以下几种。

（1）意识模糊评估法（ confusion assessment method，CAM）  CAM是目前广泛使用的谵妄评估工具，为美国Inouye等⁶⁸于1990年编制的谵妄诊断量表，适合非精神科医师使用。谵妄的诊断主要依靠四个方面的特征：①急性波动性病程；②注意力障碍；③思维紊乱；④意识水平改变。同时具备①和②，以及具备③或④其中一项即可诊断谵妄。CAM量表具有良好的敏感度（94%~100%）和特异度（90%~95%），且用时短、易于理解和使用，因此备受临床青睐（表3）。

表3.意识模糊评估法（ confusion assessment method，CAM）

满足以下标准1）+2）+3）或1）+2）+4）

（2）ICU意识模糊评估法（CAM-ICU）  CAM-ICU是ICU患者中常用的诊断工具，适合因气管插管和镇静不能进行语言交流的患者。该方法敏感性和特异性较高，且可靠有效，是美国危重病医学会推荐的ICU筛选诊断谵妄的方法⁶⁹。CAM-ICU评估首先应进行镇静深度评估，推荐使用Richmond躁动镇静分级（Richmond agitation sedation scale, RASS）。处于深度镇静或不能唤醒状态的患者不能进行谵妄评估；如果患者能够唤醒，则继续进行下一步CAM-ICU评估（表4）。 

表4. CAM-ICU诊断流程

（3）3分钟谵妄诊断量表（3-minute Diagnostic Interview for CAM，3D-CAM）  3D-CAM是对CAM量表的进一步优化。该量表包含22个问题条目，平均评估时间约为3分钟，细化了评估方法和评估标准，具有较高的实用性、敏感性和特异性⁷⁰。目前中文版3D-CAM量表经过验证具有较高的信效度⁷¹（表5）。

表5. 中文版3D-CAM

（4）护理谵妄评分表（Nursing Delirium Screening Scale, Nu-DESC） 

护理谵妄评分量表可以用于谵妄筛查，包括5项临床特征：定向障碍、行为异常、言语交流异常、错觉/幻觉和精神-运动性迟缓。每个项目根据临床症状的有无及严重程度分别计 0～2 分，0分表示不存在，1分表示轻度，2分表示中重度。最高得分为10分，总分≥1分提示存在谵妄⁷²。

（5）术后谵妄分型  ICU患者可采用CAM-ICU对谵妄进行分型诊断，在CAM-ICU量表诊断患者谵妄后，根据RASS得分判断谵妄亚型，得分为+1~+4分为高活动型，得分为0~-3分为低活动型，如果患者得分在正分和负分间波动即为混合型⁷³。

【推荐意见】建议采用经过中国人群验证的评估量表进行评估。

（二）鉴别诊断

术后谵妄常需要与下列临床症状与疾病相鉴别：

1. 痴呆  痴呆是指慢性（通常是隐匿的）的认知功能下降，也是谵妄首要的危险因素，超过2/3的痴呆患者发生过谵妄。但两者的区别主要在于，谵妄的症状会出现波动变化，即时轻时重；而痴呆则为持续的认知功能障碍，甚至可逐渐加重^74,75。

2. 术后认知功能障碍（POCD）  根据2018年关于手术及麻醉相关认知损伤的命名共识²，术后认知功能的监测和定义应该遵循美国精神障碍诊断与统计手册第五版中关于认知功能损害的相关标准，其中术后认知功能恢复延迟（delayed neurocognitive recovery）是指术后30天内的认知功能损伤，而术后认知功能障碍（POCD）是指患者在术后30天至术后1年期间存在的认知功能损伤，术后1年以上认知功能损伤的诊断则和普通人群中的标准一致。根据严重程度可分为轻度认知功能障碍（mild neurocognitive disorders）和重度认知功能障碍（major neurocognitive disorders）。但是该标准在临床中的应用价值仍有待于进一步的验证。POCD主要涉及大脑皮层的高级别功能损伤且常表现为细微的神经病理体征和神经心理障碍，因此POCD的诊断需要借助神经精神心理量表。POCD与谵妄的不同还体现在POCD患者不存在意识水平紊乱且病程较长。

3. 其它  术后谵妄还需要与其它一些中枢器质性疾病相区别，如韦尼克脑病、脑卒中、恶性肿瘤脑转移等。一般根据病史、体格检查、脑部MRI或CT检查等可鉴别。

【推荐意见】鉴别诊断有助于提高谵妄诊断准确性，必要时可邀请相关专业人员进行会诊。

五、预防

由于谵妄通常是由多种易感因素和促发因素共同作用的结果，预防谵妄也应针对多种危险因素进行干预。因此，应详细了解患者的现病史、并存疾病、药物和手术治疗情况，识别危险因素。

（一）术前准备

术前认知功能损害是术后谵妄的重要危险因素，可通过专门的护理团队进行定期交流及认知功能训练以帮助患者正确感知周围环境，从而降低谵妄的发生⁷⁶。术前积极治疗并存疾病，如抗感染、纠正代谢紊乱及改善睡眠障碍对预防谵妄有重要意义。对于术前生理功能储备降低（如活动受限、视听觉损害及衰弱）的老年患者，可通过功能训练及使用眼镜和助听设备等措施等预防谵妄。术前营养不良的患者可适当补充营养（如维生素D、蛋白质）改善营养状态⁷⁷。术前应尽量避免使用抗胆碱能药及苯二氮卓类镇静催眠类等易诱发谵妄发生的药物。谵妄风险评估与术后谵妄的处理都离不开患者家属的支持与理解，因此在手术前对高风险患者应当与患者家属充分沟通，争取他们的积极配合，更好地预防与治疗高风险患者的术后谵妄。老年患者由于身体原因术前通常服用多种药物，因此手术前应当必须评估患者日常用药，应当停止或更换具有抗胆碱能作用的药物，如异丙嗪、三环类抗抑郁药或泌尿科解痉挛药坦索罗辛（哈乐），以及苯二氮卓类睡眠诱导药物药物。

【推荐意见】对于高危患者，积极纠正易感因素、提高生理功能储备并避免可能的诱发因素可以降低谵妄发生风险。

（二）术中管理

1. 手术方式选择  术后谵妄的风险与手术创伤应激的程度相关^15-18,54。因此，选择创伤小的手术方式（如腔镜手术、介入手术等）有助于减少术后谵妄的发生。

2．麻醉方法选择  

（1）区域阻滞与全身麻醉  Bryson等⁷⁸和Mason等⁷⁹开展的Meta分析研究结果均显示两种麻醉方法对术后谵妄的影响无统计学差异。2018年的一项Meta分析纳入15项关于髋关节骨折患者的研究，结果也显示区域阻滞与全身麻醉术后谵妄发生率无明显区别⁸⁰。但最近的大样本量回顾性研究显示，下肢手术患者采用区域阻滞麻醉伴随术后谵妄风险降低⁸¹。目前仍有部分正在进行的关于区域阻滞及全身麻醉对术后谵妄影响的RCT研究，可能会提供一些新的证据^82-85。

（2）浅镇静与深镇静  STRIDE研究显示对于在腰麻下行髋关节骨折手术的老年患者，复合丙泊酚浅镇静（MOAA/S镇静评分3-5分）和深镇静（镇静评分0-2分）在术后谵妄发生率方面无统计学差异；但在术前无合并疾病的患者人群中，浅镇静可降低术后谵妄风险⁸⁶。另一项关于在腰麻下行髋关节骨折手术老年患者的研究显示，采用丙泊酚镇静时，浅镇静（BIS≥80）组较深镇静（BIS约50）组的术后谵妄发生率更低⁸⁷。

【推荐意见】对于高危患者，微创手术有助于减少谵妄发生。目前尚无充分证据说明区域阻滞麻醉与全身麻醉何种方式更优。对于在区域阻滞麻醉下接受手术且需要镇静的患者，建议给予浅镇静。

3．麻醉药物的选择  

（1）静脉麻醉与吸入麻醉  一项Meta分析显示静脉麻醉与吸入麻醉对非心脏手术后谵妄发生率的影响无明显区别，但静脉麻醉可能降低POCD风险⁸⁸。后续一项RCT研究显示丙泊酚静脉麻醉在减少POCD发生率方面优于七氟烷吸入麻醉⁸⁹。在心脏手术患者中，一项针对经导管主动脉瓣置换患者的回顾性研究显示静脉麻醉相较吸入麻醉术后谵妄发生率更低⁹⁰；但一项Meta分析则显示静脉麻醉和吸入麻醉对CABG手术后谵妄的发生率影响并无差异⁹¹。

（2）右美托咪定  右美托咪定具有镇静与镇痛作用，多项研究显示围术期预防性给予右美托咪定可降低术后谵妄风险和减少谵妄持续时间^92-94。近期一项RCT研究结果显示非心脏手术患者术中给予右美托咪定可降低谵妄发生率⁹⁵。

（3）氯胺酮  氯胺酮具有催眠和镇痛特性，其对认知功能的影响仍存在争议。一篇纳入6项RCT研究的Meta分析显示术中使用氯胺酮不能降低发生术后谵妄的风险，但可降低POCD风险⁹⁶。而一项RCT研究显示术中使用氯胺酮未降低术后谵妄发生率，反会增加幻觉、噩梦等不良事件⁹⁷。

【推荐意见】在吸入麻醉与静脉麻醉的选择方面，目前尚无推荐意见。围术期使用右美托咪定可以降低谵妄发生风险。

4. 术中监测与管理

（1）麻醉深度  早期的研究包括Meta分析显示，在基于脑电图的麻醉深度监测下管理全身麻醉可避免麻醉过深并减少术后谵妄的发生^57,98,99；但2019年的一项单中心RCT研究则显示与常规监护相比，EEG指导下的麻醉深度管理未能降低术后谵妄发生率¹⁰⁰。最近的Meta分析结果有争议，但多数显示在基于EEG的麻醉深度监测下管理全身麻醉能降低术后谵妄发生率^57,101。

（2）脑氧饱和度  2019年一项针对随机对照研究的Meta分析显示，基于近红外脑氧饱和度监测的循环管理可减少心脏手术后POCD和谵妄的发生；但对非心脏手术患者未见明显预防效果¹⁰²。此外，术中脑氧饱和度监测对其他临床结局的影响也有待进一步研究证实¹⁰²。

（3）血糖  有研究显示术中高血糖是老年患者谵妄的独立危险因素¹⁰³，但是一项随机对照研究显示术中严格控制血糖（4.4~6.1mmol/L）会轻度增加谵妄发生率¹⁰⁴。

（4）体温  低体温（核心温度<35.0°C）和高热（核心温度>40.5°C）均会导致脑功能障碍、谵妄、甚至昏迷⁶³。在最近的一项队列研究中，术中低体温伴随苏醒期谵妄风险增加¹⁰⁵。良好的术中体温管理可能减少术后谵妄的发生，但还需要研究证实。

（5）血压  术中低血压或血压高于脑血流自身调节范围可能导致术后谵妄发生风险增加^12,61；术中血压波动也是术后谵妄的预测因素⁶²。故术中合理的血压管理可能有助于减少术后谵妄的发生，仍有待研究证实¹⁰⁶。

【推荐意见】建议加强术中监测管理，全身麻醉期间应避免麻醉过深，术中应避免血压、血糖大幅波动，避免低体温或体温过高；高危患者可考虑在脑氧饱和度监测下维持循环。

（三）术后管理

1. 非药物预防措施

术后谵妄的发生通常由多种因素所致。研究表明针对谵妄危险因素的多学科、多因素综合性非药物干预可有效预防术后谵妄的发生，也是谵妄预防的核心¹⁰⁷。表6汇总了多因素干预研究中的非药物干预措施。医院老年生命计划（Hospital Elder Life Program, HELP）是由Inouye教授于1999年设计的多模式管理策略，旨在预防住院患者谵妄，已在全球200多家医院成功实施。HELP方案核心是识别患者的谵妄风险，并个体化设计干预方案，包括帮助患者重新定向、改善试视听和认知功能、早期活动、鼓励进食和非药物改善睡眠周期等⁷⁶。此后，HELP方案经过优化增添了一些干预措施如预防感染及治疗疼痛、便秘和缺氧等¹⁰⁸。一项Meta分析研究了HELP方案在预防谵妄中的有效性，纳入了14项高质量的研究，结果显示HELP方案可显著降低谵妄发生率¹⁰⁹。而对于ICU患者，Ely团队提出ABCDE集束化策略，包括A+B（每日唤醒+呼吸同步训练）、C（镇静选择）、D（谵妄监测与管理）及E（早期活动和环境管理）¹¹⁰。ABCDEF集束化干预策略是基于ABCDE策略的优化，在前述干预措施基础上，增加了A（疼痛评估、预防及管理）和F（家庭成员参与）¹¹¹。研究表明ABCDEF集束化策略可改善患者预后，包括降低谵妄发生率，降低机械通气率，减少住院时间及降低死亡率¹¹²。

表6. 多因素干预研究中的危险因素及干预措施

【推荐意见】所有患者都应给予非药物措施预防谵妄。 

2. 术后镇痛

（1）区域阻滞  越来越多的证据表明区域阻滞镇痛可能降低谵妄发生率。一项针对髋关节手术患者的RCT研究比较了持续腰丛阻滞、持续股神经阻滞及静脉自控镇痛对术后谵妄的影响，结果显示外周神经阻滞镇痛较静脉镇痛可降低术后谵妄风险¹¹³。Abou-Setta等¹¹⁴关于髋关节骨折患者的Meta分析为区域阻滞降低谵妄风险提供了中等强度的证据。但2017年的另一项Meta分析未能找到足够的高质量证据证明区域阻滞可降低谵妄风险¹¹⁵。现有证据初步揭示了区域阻滞对预防术后谵妄的优势，但仍有待高质量研究进一步证实。

（2）阿片类药物  阿片类药物是最常用的镇痛药物，但研究表明大剂量阿片类药物伴随谵妄风险增加¹¹⁶，而疼痛同样也增加谵妄风险¹¹⁷，故高危患者应做好疼痛管理同时尽量减少阿片类药物的使用。哌替啶可增加谵妄的发生，因此应避免使用哌替啶¹¹⁸。

（3）辅助镇痛药物  加巴喷丁（及其同类药普瑞巴林）常用于慢性疼痛的治疗，也用作术后镇痛的辅助药物，可改善镇痛效果并减少阿片类药物的用量¹¹⁹。但临床对照研究并没有发现加巴喷丁可减少术后谵妄^120,121。对乙酰氨基酚和非甾体抗炎药（NSAIDs）也是术后常用的辅助镇痛药；研究表明采用对乙酰氨基酚、氟比洛芬酯、帕瑞昔布进行术后多模式镇痛均可减少术后谵妄的发生^122-124。

【推荐意见】推荐在神经阻滞基础上给予多模式镇痛，以改善镇痛效果、降低谵妄发生率。

3. 药物预防

（1）抗精神病药  Neufeld等¹²⁵针对抗精神病药物预防谵妄的作用进行了Meta分析，该研究纳入了7项预防性用药研究（4项氟哌啶醇，2项利培酮，1项奥氮平），涉及1970例患者，结果显示预防性使用抗精神病药物未能减少谵妄发生。一项针对急诊住院老年患者的随机对照研究显示预防性小剂量使用氟哌啶醇（1mg，口服，每日2次）未能降低谵妄发生率¹²⁶。近期一项Meta分析同样显示预防性使用氟哌啶醇并不能降低ICU患者谵妄发生率¹²⁷。故目前并不推荐使用抗精神病药物预防术后谵妄。

（2）右美托咪定  多项Meta分析显示围术期使用右美托咪定可以降低术后谵妄发生率^92,94,128。2016年一项随机对照研究试验显示非心脏手术术后ICU患者持续输注小剂量右美托咪定可明显降低谵妄发生率¹²⁹。最近一项针对成年心脏手术患者的多中心试验显示，围术期右美托咪定未明显减术后谵妄的发生¹³⁰。需要注意的是，该研究中镇静剂量右美托咪定的输注（0.4ug/kg/h）持续至术后24h，提示不恰当的右美托咪定镇静并无益处。

（3）褪黑素和褪黑素受体激动剂  褪黑素是松果体分泌的激素，参与昼夜睡眠节律的调节，具有催眠、延长睡眠时间及提高睡眠质量的作用。多项研究显示睡眠障碍增加谵妄风险^46,66。术后褪黑素血浆浓度降低也伴随谵妄风险增加¹²⁸。因此，有研究将褪黑素及褪黑素受体激动剂用于改善睡眠、减少谵妄发生¹²⁷。2019年的一项Meta分析显示，ICU患者预防性应用褪黑素及褪黑素受体激动剂可改善睡眠时间、降低谵妄发生率，并缩短ICU停留时间¹³¹。但已有的研究多为小样本量的试验，因此仍需大样本研究进一步证实。

（4）他汀类药物  他汀类药物的使用可能降低谵妄风险，尤其是阿托伐他汀、普伐他汀和辛伐他汀¹³²，但目前研究结果并不一致^133,134。

【推荐意见】预防性给予右美托咪定可降低术后谵妄风险，但药物预防措施是否改善临床结局证据尚不充分。

六、治疗

谵妄治疗的目标是快速缓解临床症状和争取最好的预后，应首先考虑非药物治疗，药物治疗仅适用于高活动型谵妄患者。

（一）非药物治疗

首先是发现、确定和处理患者的谵妄促发因素，如疼痛、睡眠剥夺或节律紊乱、营养不良、感官障碍、感染等。应尽可能纠正可逆的促发因素，对于不能纠正的易感因素也应尽可能予以改善。同时应密切观察患者，以防患者突然发生躁动伤及自身或他人。

其次是检查患者当前用药情况，筛选可能导致谵妄症状发作的药物，停止使用或给予替代药物。给予患者支持对症处理，全身情况好转的情况下，谵妄症状可以得到改善。谵妄治疗需要给予环境和认知行为支持，非强制性对症处理妄想或幻觉对患者恢复可能更有益。回到相对熟悉的环境，由熟悉的护理人员或家庭成员护理是最好的选择。 

其它非药物治疗包括音乐治疗、按摩等。对有危险行为的患者可适当给予行动限制或使用约束带，防止其危及自身或医护人员。但注意适时评估患者的认知功能，尽早解除约束，同时与患者家属交流限制患者行动的必要性。

【推荐意见】对于任何类型的谵妄患者，应积极实施非药物干预措施。

（二）药物治疗

药物治疗仅推荐用于高活动型谵妄患者，药物治疗的目的是控制危险的躁动、运动过多或不适宜的行为。

（1）抗精神病药物  第一代抗精神病药物（如氟哌啶醇）和第二代抗精神病药物（如利培酮、奥氮平、齐拉西酮等）均被用于谵妄的治疗。被用于谵妄治疗的抗精神病药物见表7，使用时需警惕此类药物的副作用。氟哌啶醇是一种非选择性的多巴胺激动剂，经常导致心律不齐和锥体束外症状。一项针对氟哌利多的Meta分析显示，氟哌利多用于谵妄患者治疗可减轻症状的严重程度，但缺乏安慰剂对照的研究¹³⁵。最近的一项安慰剂随机对照研究显示，氟哌啶醇（最大剂量20mg/天）或齐拉西酮（最大剂量40mg/天）未能减少重症监护室内老年患者的谵妄持续时间¹³⁶。但一项针对所有抗精神病药物的Meta分析显示，治疗性应用抗精神病药物未改变谵妄的持续时间与严重程度，也未改变ICU停留时间和住院时间¹²⁵。在一项针对姑息治疗患者的随机对照研究中，口服氟哌啶醇或利培酮未能减轻谵妄症状或缩短谵妄持续时间¹³⁷。在某些已存在认知功能损害或表现为幻觉或攻击性行为的老年患者中，可以考虑使用抗精神药物，但是需要注意其潜在的心血并并发症和死亡风险^138,139。

（2）右美托咪定  一项关于右美托咪定治疗谵妄的Meta分析纳入3项RCT研究，结果显示，与安慰剂或咪达唑仑对比，右美托咪定能缩短谵妄持续时间；与氟哌啶醇相比，右美托咪定可缩短机械通气时间及ICU停留时间⁹³。

表7. 常用抗精神病药物

[1] po = 口服；iv = 静脉注射；sc = 皮下注射；im = 肌肉注射。

[2]神经安定药恶性综合征的典型表现包括肌肉僵硬、发热、自主神经功能不稳定、谵妄等，可伴有血浆肌酸磷酸激酶升高。

【推荐意见】对于躁动型谵妄患者，可以考虑给予药物治疗。推荐给予右美托咪定治疗。

参考文献

1.Oh ES, Fong TG, Hshieh TT, Inouye SK: Delirium in Older Persons: Advances in Diagnosis and Treatment. Jama 2017; 318: 1161-1174

2.Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, Oh ES, Crosby G, Berger M, Eckenhoff RG, Nomenclature Consensus Working G: Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth 2018; 121: 1005-1012

3.Kostas TR, Zimmerman KM, Rudolph JL: Improving delirium care: prevention, monitoring, and assessment. Neurohospitalist 2013; 3: 194-202

4.Rudolph JL, Harrington MB, Lucatorto MA, Chester JG, Francis J, Shay KJ, Veterans A, Delirium Working G: Validation of a medical record-based delirium risk assessment. J Am Geriatr Soc 2011; 59 Suppl 2: S289-94

5.McDaniel M, Brudney C: Postoperative delirium: etiology and management. Curr Opin Crit Care 2012; 18: 372-6

6.Spronk PE, Riekerk B, Hofhuis J, Rommes JH: Occurrence of delirium is severely underestimated in the ICU during daily care. Intensive Care Med 2009; 35: 1276-80

7.Aitken SJ, Blyth FM, Naganathan V: Incidence, prognostic factors and impact of postoperative delirium after major vascular surgery: A meta-analysis and systematic review. Vasc Med 2017; 22: 387-397

8.Brown CHt, LaFlam A, Max L, Wyrobek J, Neufeld KJ, Kebaish KM, Cohen DB, Walston JD, Hogue CW, Riley LH: Delirium After Spine Surgery in Older Adults: Incidence, Risk Factors, and Outcomes. J Am Geriatr Soc 2016; 64: 2101-2108

9.Gleason LJ, Schmitt EM, Kosar CM, Tabloski P, Saczynski JS, Robinson T, Cooper Z, Rogers SO, Jr., Jones RN, Marcantonio ER, Inouye SK: Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults. JAMA Surg 2015; 150: 1134-40

10.Crocker E, Beggs T, Hassan A, Denault A, Lamarche Y, Bagshaw S, Elmi-Sarabi M, Hiebert B, Macdonald K, Giles-Smith L, Tangri N, Arora RC: Long-Term Effects of Postoperative Delirium in Patients Undergoing Cardiac Operation: A Systematic Review. Ann Thorac Surg 2016; 102: 1391-9

11.Oldroyd C, Scholz AFM, Hinchliffe RJ, McCarthy K, Hewitt J, Quinn TJ: A systematic review and meta-analysis of factors for delirium in vascular surgical patients. J Vasc Surg 2017; 66: 1269-1279 e9

12.Scholz AF, Oldroyd C, McCarthy K, Quinn TJ, Hewitt J: Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. Br J Surg 2016; 103: e21-8

13.Bin Abd Razak HR, Yung WY: Postoperative Delirium in Patients Undergoing Total Joint Arthroplasty: A Systematic Review. J Arthroplasty 2015; 30: 1414-7

14.Gosselt AN, Slooter AJ, Boere PR, Zaal IJ: Risk factors for delirium after on-pump cardiac surgery: a systematic review. Crit Care 2015; 19: 346

15.Milstein A, Pollack A, Kleinman G, Barak Y: Confusion/delirium following cataract surgery: an incidence study of 1-year duration. Int Psychogeriatr 2002; 14: 301-6

16.Bruce AJ, Ritchie CW, Blizard R, Lai R, Raven P: The incidence of delirium associated with orthopedic surgery: a meta-analytic review. Int Psychogeriatr 2007; 19: 197-214

17.Ansaloni L, Catena F, Chattat R, Fortuna D, Franceschi C, Mascitti P, Melotti RM: Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg 2010; 97: 273-80

18.Oh YS, Kim DW, Chun HJ, Yi HJ: Incidence and risk factors of acute postoperative delirium in geriatric neurosurgical patients. J Korean Neurosurg Soc 2008; 43: 143-8

19.Shah S, Weed HG, He X, Agrawal A, Ozer E, Schuller DE: Alcohol-related predictors of delirium after major head and neck cancer surgery. Arch Otolaryngol Head Neck Surg 2012; 138: 266-71

20.Koebrugge B, van Wensen RJ, Bosscha K, Dautzenberg PL, Koning OH: Delirium after emergency/elective open and endovascular aortoiliac surgery at a surgical ward with a high-standard delirium care protocol. Vascular 2010; 18: 279-87

21.Salata K, Katznelson R, Beattie WS, Carroll J, Lindsay TF, Djaiani G: Endovascular versus open approach to aortic aneurysm repair surgery: rates of postoperative delirium. Can J Anaesth 2012; 59: 556-61

22.Gao R, Yang ZZ, Li M, Shi ZC, Fu Q: Probable risk factors for postoperative delirium in patients undergoing spinal surgery. Eur Spine J 2008; 17: 1531-7

23.Brouquet A, Cudennec T, Benoist S, Moulias S, Beauchet A, Penna C, Teillet L, Nordlinger B: Impaired mobility, ASA status and administration of tramadol are risk factors for postoperative delirium in patients aged 75 years or more after major abdominal surgery. Ann Surg 2010; 251: 759-65

24.Olin K, Eriksdotter-Jonhagen M, Jansson A, Herrington MK, Kristiansson M, Permert J: Postoperative delirium in elderly patients after major abdominal surgery. Br J Surg 2005; 92: 1559-64

25.Mu DL, Wang DX, Li LH, Shan GJ, Li J, Yu QJ, Shi CX: High serum cortisol level is associated with increased risk of delirium after coronary artery bypass graft surgery: a prospective cohort study. Crit Care 2010; 14: R238

26.Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW: Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010; 38: 1513-20

27.Bai J, Liang Y, Zhang P, Liang X, He J, Wang J, Wang Y: Association between postoperative delirium and mortality in elderly patients undergoing hip fractures surgery: a meta-analysis. Osteoporos Int 2019

28.Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW: Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006; 104: 21-6

29.Lee HB, Mears SC, Rosenberg PB, Leoutsakos JM, Gottschalk A, Sieber FE: Predisposing factors for postoperative delirium after hip fracture repair in individuals with and without dementia. J Am Geriatr Soc 2011; 59: 2306-13

30.Morimoto Y, Yoshimura M, Utada K, Setoyama K, Matsumoto M, Sakabe T: Prediction of postoperative delirium after abdominal surgery in the elderly. J Anesth 2009; 23: 51-6

31.Greene NH, Attix DK, Weldon BC, Smith PJ, McDonagh DL, Monk TG: Measures of executive function and depression identify patients at risk for postoperative delirium. Anesthesiology 2009; 110: 788-95

32.van Munster BC, de Rooij S, Yazdanpanah M, Tienari PJ, Pitkala KH, Osse RJ, Adamis D, Smit O, van der Steen MS, van Houten M, Rahkonen T, Sulkava R, Laurila JV, Strandberg TE, Tulen JHM, Zwang L, MacDonald AJD, Treloar A, Sijbrands EJG, Zwinderman AH, Korevaar JC: The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 648-655

33.Nekrosius D, Kaminskaite M, Jokubka R, Pranckeviciene A, Lideikis K, Tamasauskas A, Bunevicius A: Association of COMT Val(158)Met Polymorphism With Delirium Risk and Outcomes After Traumatic Brain Injury. J Neuropsychiatry Clin Neurosci 2019; 31: 298-305

34.Kazmierski J, Sieruta M, Banys A, Jaszewski R, Sobow T, Liberski P, Kloszewska I: The assessment of the T102C polymorphism of the 5HT2a receptor gene, 3723G/A polymorphism of the NMDA receptor 3A subunit gene (GRIN3A) and 421C/A polymorphism of the NMDA receptor 2B subunit gene (GRIN2B) among cardiac surgery patients with and without delirium. Gen Hosp Psychiatry 2014; 36: 753-6

35.Lindroth H, Bratzke L, Purvis S, Brown R, Coburn M, Mrkobrada M, Chan MTV, Davis DHJ, Pandharipande P, Carlsson CM, Sanders RD: Systematic review of prediction models for delirium in the older adult inpatient. BMJ Open 2018; 8: e019223

36.Marcantonio ER, Goldman L, Mangione CM, Ludwig LE, Muraca B, Haslauer CM, Donaldson MC, Whittemore AD, Sugarbaker DJ, Poss R, et al.: A clinical prediction rule for delirium after elective noncardiac surgery. JAMA 1994; 271: 134-9

37.Nomura Y, Nakano M, Bush B, Tian J, Yamaguchi A, Walston J, Hasan R, Zehr K, Mandal K, LaFlam A, Neufeld KJ, Kamath V, Hogue CW, Brown CHt: Observational Study Examining the Association of Baseline Frailty and Postcardiac Surgery Delirium and Cognitive Change. Anesth Analg 2019; 129: 507-514

38.Leung JM, Tsai TL, Sands LP: Brief report: preoperative frailty in older surgical patients is associated with early postoperative delirium. Anesth Analg 2011; 112: 1199-201

39.Zhang DF, Su X, Meng ZT, Cui F, Li HL, Wang DX, Li XY: Preoperative severe hypoalbuminemia is associated with an increased risk of postoperative delirium in elderly patients: Results of a secondary analysis. J Crit Care 2018; 44: 45-50

40.Velayati A, Vahdat Shariatpanahi M, Dehghan S, Zayeri F, Vahdat Shariatpanahi Z: Vitamin D and Postoperative Delirium After Coronary Artery Bypass Grafting: A Prospective Cohort Study. J Cardiothorac Vasc Anesth 2020

41.Lawlor PG: Delirium and dehydration: some fluid for thought? Support Care Cancer 2002; 10: 445-54

42.Chen W, Ke X, Wang X, Sun X, Wang J, Yang G, Xia H, Zhang L: Prevalence and risk factors for postoperative delirium in total joint arthroplasty patients: A prospective study. Gen Hosp Psychiatry 2017; 46: 55-61

43.Krzych LJ, Wybraniec MT, Krupka-Matuszczyk I, Skrzypek M, Bolkowska A, Wilczynski M, Bochenek AA: Complex assessment of the incidence and risk factors of delirium in a large cohort of cardiac surgery patients: a single-center 6-year experience. Biomed Res Int 2013; 2013: 835850

44.Neuro VI: Perioperative covert stroke in patients undergoing non-cardiac surgery (NeuroVISION): a prospective cohort study. Lancet 2019; 394: 1022-1029

45.Rudolph JL, Marcantonio ER: Postoperative delirium: acute change with long-term implications. Anesth Analg 2011; 112: 1202-11

46.Fadayomi AB, Ibala R, Bilotta F, Westover MB, Akeju O: A Systematic Review and Meta-Analysis Examining the Impact of Sleep Disturbance on Postoperative Delirium. Crit Care Med 2018; 46: e1204-e1212

47.Lalonde B, Uldall KK, Berghuis JP: Delirium in AIDS patients: discrepancy between occurrence and health care provider identification. AIDS Patient Care STDS 1996; 10: 282-7

48.Breitbart W, Alici Y: Agitation and delirium at the end of life: "We couldn't manage him". JAMA 2008; 300: 2898-910, E1

49.Benoit AG, Campbell BI, Tanner JR, Staley JD, Wallbridge HR, Biehl DR, Bradley BD, Louridas G, Guzman RP, Fromm RA: Risk factors and prevalence of perioperative cognitive dysfunction in abdominal aneurysm patients. J Vasc Surg 2005; 42: 884-90

50.Litaker D, Locala J, Franco K, Bronson DL, Tannous Z: Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry 2001; 23: 84-9

51.Voyer P, Richard S, Doucet L, Carmichael PH: Predisposing factors associated with delirium among demented long-term care residents. Clin Nurs Res 2009; 18: 153-71

52.Clegg A, Young JB: Review: Insufficient evidence exists about which drugs are associated with delirium; benzodiazepines may increase risk. Ann Intern Med 2011; 154: JC6-10

53.Campbell N, Boustani M, Limbil T, Ott C, Fox C, Maidment I, Schubert CC, Munger S, Fick D, Miller D, Gulati R: The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging 2009; 4: 225-33

54.Dasgupta M, Dumbrell AC: Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J Am Geriatr Soc 2006; 54: 1578-89

55.Rolfson DB, McElhaney JE, Rockwood K, Finnegan BA, Entwistle LM, Wong JF, Suarez-Almazor ME: Incidence and risk factors for delirium and other adverse outcomes in older adults after coronary artery bypass graft surgery. Can J Cardiol 1999; 15: 771-6

56.Piao J, Jin Y, Lee SM: Triggers and nursing influences on delirium in intensive care units. Nurs Crit Care 2018; 23: 8-15

57.Bocskai T, Kovács M, Szakács Z, Gede N, Hegyi P, Varga G, Pap I, Tóth I, Révész P, Szanyi I, Németh A, Gerlinger I, Karádi K, Lujber L: Is the bispectral index monitoring protective against postoperative cognitive decline? A systematic review with meta-analysis. PLoS One 2020; 15: e0229018

58.Schoen J, Meyerrose J, Paarmann H, Heringlake M, Hueppe M, Berger KU: Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: a prospective observational trial. Crit Care 2011; 15: R218

59.Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM, 3rd, Rodriguez AL, Magovern CJ, Zaubler T, Freundlich K, Parr GV: Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg 2009; 87: 36-44; discussion 44-5

60.Wesselink EM, Kappen TH, van Klei WA, Dieleman JM, van Dijk D, Slooter AJ: Intraoperative hypotension and delirium after on-pump cardiac surgery. Br J Anaesth 2015; 115: 427-33

61.Hori D, Brown C, Ono M, Rappold T, Sieber F, Gottschalk A, Neufeld KJ, Gottesman R, Adachi H, Hogue CW: Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium. Br J Anaesth 2014; 113: 1009-17

62.Hirsch J, DePalma G, Tsai TT, Sands LP, Leung JM: Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery. Br J Anaesth 2015; 115: 418-26

63.Cheshire WP, Jr.: Thermoregulatory disorders and illness related to heat and cold stress. Auton Neurosci 2016; 196: 91-104

64.Lat I, McMillian W, Taylor S, Janzen JM, Papadopoulos S, Korth L, Ehtisham A, Nold J, Agarwal S, Azocar R, Burke P: The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 2009; 37: 1898-905

65.Martin BJ, Buth KJ, Arora RC, Baskett RJ: Delirium as a predictor of sepsis in post-coronary artery bypass grafting patients: a retrospective cohort study. Crit Care 2010; 14: R171

66.Evans JL, Nadler JW, Preud'homme XA, Fang E, Daughtry RL, Chapman JB, Attarian D, Wellman S, Krystal AD: Pilot prospective study of post-surgery sleep and EEG predictors of post-operative delirium. Clin Neurophysiol 2017; 128: 1421-1425

67.Association AP: Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Washington, DC, American Psychiatric Society, 2013

68.Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI: Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990; 113: 941-8

69.Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R: Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). Jama 2001; 286: 2703-10

70.Marcantonio ER, Ngo LH, O'Connor M, Jones RN, Crane PK, Metzger ED, Inouye SK: 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Ann Intern Med 2014; 161: 554-61

71.Mu DL, Ding PP, Zhou SZ, Liu MJ, Sun XY, Li XY, Wang DX: Cross-cultural adaptation and validation of the 3D-CAM Chinese version in surgical ICU patients. BMC Psychiatry 2020; 20: 133

72.Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA: Fast, systematic, and continuous delirium assessment in hospitalized patients: the nursing delirium screening scale. J Pain Symptom Manage 2005; 29: 368-75

73.Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK, Ely EW: Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc 2006; 54: 479-84

74.Joshi A, Krishnamurthy VB, Purichia H, Hollar-Wilt L, Bixler E, Rapp M: "What's in a name?" Delirium by any other name would be as deadly. A review of the nature of delirium consultations. J Psychiatr Pract 2012; 18: 413-8

75.Downing LJ, Caprio TV, Lyness JM: Geriatric psychiatry review: differential diagnosis and treatment of the 3 D's - delirium, dementia, and depression. Curr Psychiatry Rep 2013; 15: 365

76.Inouye SK, Bogardus ST, Jr., Charpentier PA, Leo-Summers L, Acampora D, Holford TR, Cooney LM, Jr.: A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 1999; 340: 669-76

77.O'Mahony R, Murthy L, Akunne A, Young J, Guideline Development G: Synopsis of the National Institute for Health and Clinical Excellence guideline for prevention of delirium. Ann Intern Med 2011; 154: 746-51

78.Bryson GL, Wyand A: Evidence-based clinical update: general anesthesia and the risk of delirium and postoperative cognitive dysfunction. Can J Anaesth 2006; 53: 669-77

79.Mason SE, Noel-Storr A, Ritchie CW: The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis 2010; 22 Suppl 3: 67-79

80.Patel V, Champaneria R, Dretzke J, Yeung J: Effect of regional versus general anaesthesia on postoperative delirium in elderly patients undergoing surgery for hip fracture: a systematic review. BMJ Open 2018; 8: e020757

81.Ahn EJ, Kim HJ, Kim KW, Choi HR, Kang H, Bang SR: Comparison of general anaesthesia and regional anaesthesia in terms of mortality and complications in elderly patients with hip fracture: a nationwide population-based study. BMJ Open 2019; 9: e029245

82.Li YW, Li HJ, Li HJ, Feng Y, Yu Y, Guo XY, Li Y, Zhao BJ, Hu XY, Zuo MZ, Zhang HY, Wang MR, Ji P, Yan XY, Wu YF, Wang DX: Effects of two different anesthesia-analgesia methods on incidence of postoperative delirium in elderly patients undergoing major thoracic and abdominal surgery: study rationale and protocol for a multicenter randomized controlled trial. BMC Anesthesiol 2015; 15: 144

83.Neuman MD, Ellenberg SS, Sieber FE, Magaziner JS, Feng R, Carson JL, Investigators R: Regional versus General Anesthesia for Promoting Independence after Hip Fracture (REGAIN): protocol for a pragmatic, international multicentre trial. BMJ Open 2016; 6: e013473

84.Li T, Yeung J, Li J, Zhang Y, Melody T, Gao Y, Wang Y, Lian Q, Gao F, Investigators RA-D: Comparison of regional with general anaesthesia on postoperative delirium (RAGA-delirium) in the older patients undergoing hip fracture surgery: study protocol for a multicentre randomised controlled trial. BMJ Open 2017; 7: e016937

85.Kowark A, Adam C, Ahrens J, Bajbouj M, Bollheimer C, Borowski M, Dodel R, Dolch M, Hachenberg T, Henzler D, Hildebrand F, Hilgers RD, Hoeft A, Isfort S, Kienbaum P, Knobe M, Knuefermann P, Kranke P, Laufenberg-Feldmann R, Nau C, Neuman MD, Olotu C, Rex C, Rossaint R, Sanders RD, Schmidt R, Schneider F, Siebert H, Skorning M, Spies C, Vicent O, Wappler F, Wirtz DC, Wittmann M, Zacharowski K, Zarbock A, Coburn M, i Hsg: Improve hip fracture outcome in the elderly patient (iHOPE): a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia. BMJ Open 2018; 8: e023609

86.Sieber FE, Neufeld KJ, Gottschalk A, Bigelow GE, Oh ES, Rosenberg PB, Mears SC, Stewart KJ, Ouanes JP, Jaberi M, Hasenboehler EA, Li T, Wang NY: Effect of Depth of Sedation in Older Patients Undergoing Hip Fracture Repair on Postoperative Delirium: The STRIDE Randomized Clinical Trial. JAMA Surg 2018; 153: 987-995

87.Sieber FE, Zakriya KJ, Gottschalk A, Blute MR, Lee HB, Rosenberg PB, Mears SC: Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc 2010; 85: 18-26

88.Miller D, Lewis SR, Pritchard MW, Schofield-Robinson OJ, Shelton CL, Alderson P, Smith AF: Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery. Cochrane Database Syst Rev 2018; 8: Cd012317

89.Zhang Y, Shan GJ, Zhang YX, Cao SJ, Zhu SN, Li HJ, Ma D, Wang DX, First Study of Perioperative Organ Protection i: Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults. Br J Anaesth 2018; 121: 595-604

90.Goins AE, Smeltz A, Ramm C, Strassle PD, Teeter EG, Vavalle JP, Kolarczyk L: General Anesthesia for Transcatheter Aortic Valve Replacement: Total Intravenous Anesthesia is Associated with Less Delirium as Compared to Volatile Agent Technique. J Cardiothorac Vasc Anesth 2018; 32: 1570-1577

91.Jiao XF, Lin XM, Ni XF, Li HL, Zhang C, Yang CS, Song HX, Yi QS, Zhang LL: Volatile anesthetics versus total intravenous anesthesia in patients undergoing coronary artery bypass grafting: An updated meta-analysis and trial sequential analysis of randomized controlled trials. PLoS One 2019; 14: e0224562

92.Wu M, Liang Y, Dai Z, Wang S: Perioperative dexmedetomidine reduces delirium after cardiac surgery: A meta-analysis of randomized controlled trials. J Clin Anesth 2018; 50: 33-42

93.Flukiger J, Hollinger A, Speich B, Meier V, Tontsch J, Zehnder T, Siegemund M: Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis. Ann Intensive Care 2018; 8: 92

94.Pan H, Liu C, Ma X, Xu Y, Zhang M, Wang Y: Perioperative dexmedetomidine reduces delirium in elderly patients after non-cardiac surgery: a systematic review and meta-analysis of randomized-controlled trials. Can J Anaesth 2019; 66: 1489-1500

95.Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, Ma D, Wang DX: Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. Br J Surg 2020; 107: e123-e132

96.Hovaguimian F, Tschopp C, Beck-Schimmer B, Puhan M: Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta-analysis. Acta Anaesthesiol Scand 2018; 62: 1182-1193

97.Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA, Group PR: Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet 2017; 390: 267-275

98.Orena EF, King AB, Hughes CG: The role of anesthesia in the prevention of postoperative delirium: a systematic review. Minerva Anestesiol 2016; 82: 669-83

99.Punjasawadwong Y, Chau-In W, Laopaiboon M, Punjasawadwong S, Pin-On P: Processed electroencephalogram and evoked potential techniques for amelioration of postoperative delirium and cognitive dysfunction following non-cardiac and non-neurosurgical procedures in adults. Cochrane Database Syst Rev 2018; 5: CD011283

100.Wildes TS, Mickle AM, Ben Abdallah A, Maybrier HR, Oberhaus J, Budelier TP, Kronzer A, McKinnon SL, Park D, Torres BA, Graetz TJ, Emmert DA, Palanca BJ, Goswami S, Jordan K, Lin N, Fritz BA, Stevens TW, Jacobsohn E, Schmitt EM, Inouye SK, Stark S, Lenze EJ, Avidan MS, Group ER: Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial. JAMA 2019; 321: 473-483

101.Sun Y, Ye F, Wang J, Ai P, Wei C, Wu A, Xie W: Electroencephalography-Guided Anesthetic Delivery for Preventing Postoperative Delirium in Adults: An Updated Meta-analysis. Anesth Analg 2020

102.Ortega-Loubon C, Herrera-Gomez F, Bernuy-Guevara C, Jorge-Monjas P, Ochoa-Sangrador C, Bustamante-Munguira J, Tamayo E, Alvarez FJ: Near-Infrared Spectroscopy Monitoring in Cardiac and Noncardiac Surgery: Pairwise and Network Meta-Analyses. J Clin Med 2019; 8

103.Windmann V, Spies C, Knaak C, Wollersheim T, Piper SK, Vorderwulbecke G, Kurpanik M, Kuenz S, Lachmann G: Intraoperative hyperglycemia increases the incidence of postoperative delirium. Minerva Anestesiol 2019; 85: 1201-1210

104.Saager L, Duncan AE, Yared JP, Hesler BD, You J, Deogaonkar A, Sessler DI, Kurz A: Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery. Anesthesiology 2015; 122: 1214-23

105.Zhang Y, He ST, Nie B, Li XY, Wang DX: Emergence delirium is associated with increased postoperative delirium in elderly: a prospective observational study. J Anesth 2020; 34: 675-687

106.Langer T, Santini A, Zadek F, Chiodi M, Pugni P, Cordolcini V, Bonanomi B, Rosini F, Marcucci M, Valenza F, Marenghi C, Inglese S, Pesenti A, Gattinoni L: Intraoperative hypotension is not associated with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia for surgery: results of a randomized controlled pilot trial. J Clin Anesth 2019; 52: 111-118

107.Kang J, Lee M, Ko H, Kim S, Yun S, Jeong Y, Cho Y: Effect of nonpharmacological interventions for the prevention of delirium in the intensive care unit: A systematic review and meta-analysis. J Crit Care 2018; 48: 372-384

108.Yue J, Tabloski P, Dowal SL, Puelle MR, Nandan R, Inouye SK: NICE to HELP: operationalizing National Institute for Health and Clinical Excellence guidelines to improve clinical practice. J Am Geriatr Soc 2014; 62: 754-61

109.Hshieh TT, Yang T, Gartaganis SL, Yue J, Inouye SK: Hospital Elder Life Program: Systematic Review and Meta-analysis of Effectiveness. Am J Geriatr Psychiatry 2018; 26: 1015-1033

110.Vasilevskis EE, Pandharipande PP, Girard TD, Ely EW: A screening, prevention, and restoration model for saving the injured brain in intensive care unit survivors. Crit Care Med 2010; 38: S683-91

111.Marra A, Ely EW, Pandharipande PP, Patel MB: The ABCDEF Bundle in Critical Care. Crit Care Clin 2017; 33: 225-243

112.Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, Aldrich JM, Barr J, Byrum D, Carson SS, Devlin JW, Engel HJ, Esbrook CL, Hargett KD, Harmon L, Hielsberg C, Jackson JC, Kelly TL, Kumar V, Millner L, Morse A, Perme CS, Posa PJ, Puntillo KA, Schweickert WD, Stollings JL, Tan A, D'Agostino McGowan L, Ely EW: Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Crit Care Med 2019; 47: 3-14

113.Marino J, Russo J, Kenny M, Herenstein R, Livote E, Chelly JE: Continuous lumbar plexus block for postoperative pain control after total hip arthroplasty. A randomized controlled trial. J Bone Joint Surg Am 2009; 91: 29-37

114.Abou-Setta AM, Beaupre LA, Rashiq S, Dryden DM, Hamm MP, Sadowski CA, Menon MR, Majumdar SR, Wilson DM, Karkhaneh M, Mousavi SS, Wong K, Tjosvold L, Jones CA: Comparative effectiveness of pain management interventions for hip fracture: a systematic review. Ann Intern Med 2011; 155: 234-45

115.Guay J, Parker MJ, Griffiths R, Kopp S: Peripheral nerve blocks for hip fractures. Cochrane Database Syst Rev 2017; 5: CD001159

116.Gaudreau JD, Gagnon P, Roy MA, Harel F, Tremblay A: Opioid medications and longitudinal risk of delirium in hospitalized cancer patients. Cancer 2007; 109: 2365-73

117.Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM: Postoperative delirium: the importance of pain and pain management. Anesth Analg 2006; 102: 1267-73

118.Swart LM, van der Zanden V, Spies PE, de Rooij SE, van Munster BC: The Comparative Risk of Delirium with Different Opioids: A Systematic Review. Drugs Aging 2017; 34: 437-443

119.Dauri M, Faria S, Gatti A, Celidonio L, Carpenedo R, Sabato AF: Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences. Curr Drug Targets 2009; 10: 716-33

120.Dighe K, Clarke H, McCartney CJ, Wong CL: Perioperative gabapentin and delirium following total knee arthroplasty: a post-hoc analysis of a double-blind randomized placebo-controlled trial. Can J Anaesth 2014; 61: 1136-7

121.Leung JM, Sands LP, Chen N, Ames C, Berven S, Bozic K, Burch S, Chou D, Covinsky K, Deviren V, Kinjo S, Kramer JH, Ries M, Tay B, Vail T, Weinstein P, Chang S, Meckler G, Newman S, Tsai T, Voss V, Youngblom E: Perioperative Gabapentin Does Not Reduce Postoperative Delirium in Older Surgical Patients: A Randomized Clinical Trial. Anesthesiology 2017; 127: 633-644

122.王晓山, 刘沛, 王东信, 李世忠, 丁婷, 贾茜茜: 氟比洛芬酯复合舒芬太尼镇痛对骨科患者术后谵妄发生率的影响. 临床麻醉学杂志 2012; 028: 152-154

123.Mu DL, Zhang DZ, Wang DX, Wang G, Li CJ, Meng ZT, Li YW, Liu C, Li XY: Parecoxib Supplementation to Morphine Analgesia Decreases Incidence of Delirium in Elderly Patients After Hip or Knee Replacement Surgery: A Randomized Controlled Trial. Anesth Analg 2017; 124: 1992-2000

124.Subramaniam B, Shankar P, Shaefi S, Mueller A, O'Gara B, Banner-Goodspeed V, Gallagher J, Gasangwa D, Patxot M, Packiasabapathy S, Mathur P, Eikermann M, Talmor D, Marcantonio ER: Effect of Intravenous Acetaminophen vs Placebo Combined With Propofol or Dexmedetomidine on Postoperative Delirium Among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. Jama 2019; 321: 686-696

125.Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM: Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc 2016; 64: 705-14

126.Schrijver EJM, de Vries OJ, van de Ven PM, Bet PM, Kamper AM, Diepeveen SHA, van Marum RJ, van Strien AM, Anten S, Lagaay AM, Boelaarts L, Bloemers FW, Kramer MHH, Nanayakkara PWB: Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial. Age Ageing 2018; 47: 48-55

127.Lin P, Zhang J, Shi F, Liang ZA: Can haloperidol prophylaxis reduce the incidence of delirium in critically ill patients in intensive care units? A systematic review and meta-analysis. Heart Lung 2020

128.Zeng H, Li Z, He J, Fu W: Dexmedetomidine for the prevention of postoperative delirium in elderly patients undergoing noncardiac surgery: A meta-analysis of randomized controlled trials. PLoS One 2019; 14: e0218088

129.Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D: Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 2016; 388: 1893-1902

130.Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, Hargrave J, Gillinov M, Trombetta C, Ayad S, Hassan M, Feider A, Howard-Quijano K, Ruetzler K, Sessler DI: Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet 2020; 396: 177-185

131.Zhang Q, Gao F, Zhang S, Sun W, Li Z: Prophylactic use of exogenous melatonin and melatonin receptor agonists to improve sleep and delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials. Sleep Breath 2019; 23: 1059-1070

132.Mather JF, Corradi JP, Waszynski C, Noyes A, Duan Y, Grady J, Dicks R: Statin and Its Association With Delirium in the Medical ICU. Crit Care Med 2017; 45: 1515-1522

133.Page VJ, Casarin A, Ely EW, Zhao XB, McDowell C, Murphy L, McAuley DF: Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2017; 5: 727-737

134.Vallabhajosyula S, Kanmanthareddy A, Erwin PJ, Esterbrooks DJ, Morrow LE: Role of statins in delirium prevention in critical ill and cardiac surgery patients: A systematic review and meta-analysis. J Crit Care 2017; 37: 189-196

135.Schrijver EJ, de Graaf K, de Vries OJ, Maier AB, Nanayakkara PW: Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence. Eur J Intern Med 2016; 27: 14-23

136.Girard TD, Exline MC, Carson SS, Hough CL, Rock P, Gong MN, Douglas IS, Malhotra A, Owens RL, Feinstein DJ, Khan B, Pisani MA, Hyzy RC, Schmidt GA, Schweickert WD, Hite RD, Bowton DL, Masica AL, Thompson JL, Chandrasekhar R, Pun BT, Strength C, Boehm LM, Jackson JC, Pandharipande PP, Brummel NE, Hughes CG, Patel MB, Stollings JL, Bernard GR, Dittus RS, Ely EW: Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med 2018; 379: 2506-2516

137.Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, Sanderson C, Hardy J, Le B, Eckermann S, McCaffrey N, Devilee L, Fazekas B, Hill M, Currow DC: Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med 2017; 177: 34-42

138.Yunusa I, El Helou ML: The Use of Risperidone in Behavioral and Psychological Symptoms of Dementia: A Review of Pharmacology, Clinical Evidence, Regulatory Approvals, and Off-Label Use. Front Pharmacol 2020; 11: 596

139.Pluta MP, Dziech M, Czempik PF, Szczepańska AJ, Krzych Ł J: Antipsychotic Drugs in Prevention of Postoperative Delirium-What Is Known in 2020? Int J Environ Res Public Health 2020; 17: 6069