重症创伤患者相关精神障碍的研究进展

游平飞; 金红旭

doi:10.3877/cma.j.issn.2096-1537.2023.04.010

中华重症医学电子杂志 >

2023 , Vol. 09 >Issue 04: 396 - 401

DOI: https://doi.org/10.3877/cma.j.issn.2096-1537.2023.04.010

综述

重症创伤患者相关精神障碍的研究进展

游平飞 ,
金红旭 ^,^†

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110011　沈阳，中国医科大学北方医院急诊医学科；110011　沈阳，北部战区总医院急诊医学科
110011　沈阳，北部战区总医院急诊医学科

通信作者：金红旭，Email：hongxuj@126.com

Copy editor: 卫轲

收稿日期: 2022-07-27

网络出版日期: 2024-02-04

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未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计，除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。本刊为电子期刊，以网刊形式出版。

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Advance of mental disorders in severe trauma patients

Pingfei You ,
Hongxu Jin ^,^†

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Department of Emergency, Beifang Hospital of China Medical University, Shenyang 110011, China; Department of Emergency, General Hospital of Northern Theater Command, Shenyang 110011, China
Department of Emergency, General Hospital of Northern Theater Command, Shenyang 110011, China

Corresponding author: Jin Hongxu, Email: hongxuj@126.com

Received date: 2022-07-27

Online published: 2024-02-04

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No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.

All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

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摘要

重症创伤是现代非正常死亡原因中最为主要的、伴随着人体多部位的损伤。其不仅具有突发性强、受创面积大及常伴有各种致命性的损伤等特点，也可以引起创伤相关的精神障碍。在这类患者中，创伤可以作为应激源引起中枢和外周神经系统、内分泌器官和体液系统相互作用，引发相关精神障碍，如创伤后应激障碍（PTSD）、谵妄、焦虑、抑郁以及ICU后综合征（PICS）等。考虑到目前对重症创伤患者合并精神障碍认知仍不足，本文将围绕各类精神障碍的特点、机制以及干预治疗的最新研究进行综述，以期为临床干预重症创伤患者相关精神障碍提供参考与建议。

关键词： 重症创伤; 精神障碍; 诊断; 机制; 治疗

本文引用格式

游平飞 , 金红旭 . 重症创伤患者相关精神障碍的研究进展[J]. 中华重症医学电子杂志, 2023 , 09(04) : 396 -401 . DOI: 10.3877/cma.j.issn.2096-1537.2023.04.010

Abstract

Severe trauma is most important cause of abnormal death in modern life, accompanied with injuries in many parts of body. It not only contains characteristics of sudden paroxysm, large trauma area and various fatal injuries, but also causes trauma-related mental disorders. In these patients, trauma is a stressor to cause mental disorder, such as post-traumatic stress disorder (PTSD), anxiety, depression, delirium, and post-intensive care syndrome (PICS) through interaction between central and peripheral nervous systems, endocrine organs and humoral systems. Considering that there is still insufficient recognition of severe trauma related mental disorders, and research in this field is a hot topic at present, this article reviews the latest research on characteristics,mechanisms, and treatment of mental disorders, in order to provide reference and advice for clinical intervention of severe trauma-related mental disorders.

Key words： Severe Trauma; Mental disorder; Diagnosis; Mechanism; Treatment

重症创伤后相关精神障碍是指患者遭受重症创伤这一诱发因素后延迟出现的精神障碍，具有发病率高、治疗病程长、预后差等特点。重症创伤对于机体的危害不仅仅与局部组织损伤的严重程度有关，引发的相关精神障碍也会加重对器官功能的损伤，带来更严重的后果。因此，对重症创伤及其相关精神障碍的特点、机制及治疗等进行综述十分必要。

一、重症创伤的评估标准

创伤是指机械性致伤因素作用于人体组织造成的组织结构完整性的破坏或功能障碍。损伤严重度评分（injury severity scores，ISS）是根据创伤患者损伤的解剖部位组织器官类型来界定损伤严重程度且将ISS≥16分定义为重症创伤^［1］。为了更好地实现早期的临床救治以及后期并发症的处理，临床实践中诞生了ISS、校正创伤评分（revised trauma score，RTS）、创伤严重程度评分（circulation、respiration、abdomen、motor、speech，CRAMS）^［2］以及急性生理学及慢性健康状况评分（acute physiology and chronic health evaluation Ⅱ，APACHE Ⅱ）等评分系统。其中APACHE Ⅱ是ICU应用最广泛、最具权威性的危重症病情评价系统，用来预示患者疾病的结局，其特异度高达97.3%^［3］，评分＞25分^［4］是病情危重、预后较差的征兆。除了通过评分系统对重症创伤患者展开及时的救治外，还需临床工作者了解重症创伤患者相关精神障碍的常见类型。

二、重症创伤患者常见精神障碍的分类

（一）创伤后应激障碍

创伤后应激障碍（post-traumatic stress disorder，PTSD）是暴露于创伤事件后出现的一种精神障碍，其核心症状群包括：创伤性体验的反复重现、持续回避与创伤事件相关的刺激、持续的警觉增高和创伤事件相关的认知和心境方面的消极改变。Carlier等^［5］的研究发现在荷兰Bijlmermeer空难中的幸存者发生PTSD的概率为26%。Zhang等^［6］的研究发现在汶川地震中遭受重症创伤的幸存者PTSD的发病率可高达80%。Asuquo等^［7］在调研后发现在一次重型交通事故后，发生PTSD的概率为41.3%。研究显示创伤后PTSD的发生率与暴露于该创伤事件的严重程度如身体损伤程度、直接生命风险等呈正相关（P＜0.01）^{［8, 9］}。由此重症创伤患者PTSD的发病率显著高于普通创伤患者PTSD的发病率。

（二）谵妄

谵妄是由多种原因引起的患者一过性意识混乱并伴有认知功能损害。创伤是谵妄发生的一个独立相关因素^［10］，而重症创伤作为全球个体致残致死的一大危害，具有病情危重、病死率高的特点。相关研究^{［11, 12, 13］}报告，重症创伤患者发生谵妄发生率为20%~60%。目前临床上重症创伤患者谵妄评估主要方式有谵妄认知测试（cognitive test for delirium，CTD）、困惑评估方法（confusion assessment method for the ICU，CAM-ICU）、查姆量表（NEECHAM scale）和谵妄检测分数（delirium detection score，DDS）^［14］。其中困惑评估方法CAM-ICU应用简单、准确、易于掌握，其敏感度和特异度分别为95%~100%和93%~100%，95%CI为0.89~0.99^{［15, 16, 17］}。重症创伤患者谵妄会导致其院内死亡风险增加近2倍^［18］，住院时间平均延长17 d^［19］，医疗费用增加，部分出院患者出院后出现长期认知功能障碍（P＜0.01）^［20］，严重影响其远期生活质量^［21］。

（三）焦虑、抑郁

抑郁是由各种原因引起的以心情低落为主要症状的一种疾病。而焦虑则表现为过度的担忧、恐惧、紧张并伴有疲劳、易怒等。压力、创伤是引起和发展心理障碍疾病的关键因素，且创伤是诱发焦虑、抑郁的一个主要原因。Fierman等^［22］在早期焦虑症的研究调查中发现，27%的受试者报告受到重症创伤，且抑郁症患者都有创伤暴露的共病史^［23］。在Osborn等^［24］对非穿透性脑损伤的样本分析中，约30%的重症脑部创伤患者患有抑郁症。Cénat等^［25］在对海地地震幸存者的一次荟萃分析中发现，发生抑郁的概率为32.1%，而发生焦虑的概率为20.4%。研究发现，重症创伤相关精神障碍的患者在病程中会出现严重后果如急诊手术干预率降低、患心血管和代谢性疾病等并发症发病率增加、住院时间延长近10 d等，这些严重后果极大降低了患者的预期寿命^{［26, 27］}。

（四）ICU后综合征

ICU后综合征（post-intensive care syndrome，PICS）是指对于受到重症创伤的患者在ICU治疗期间伤口的疼痛是其最常见的记忆，安装在身体上的各种监护设备，以及病房的氛围，加上孤独、恐惧的种种自我感受导致患者在转出监护室时出现的心理、生理和认知等各方面的功能性障碍^［28］。PICS的风险因素在一定程度上取决于认知、精神以及在物理领域。其主要包括了低教育水平、谵妄、超过7 d的机械通气、败血症、多器官功能障碍等^{［29, 30, 31］}。研究发现^［29］在ICU中，60%的重症患者会出现PICS。由于目前缺乏针对此类患者特定的筛查工具，临床上暂时使用简易精神状态检查评估（mini-mental state examination，MMSE）、简易智力状态评估量表（mini cognitive assessment test，Mini-Cog）来评估患者是否存在认知障碍^［32］，但其缺陷是不能作为6个月以及长期的认知预测评估。由此PICS的有效诊断和早期评估是一项具有挑战性的工作。

三、重症创伤患者精神障碍的危险因素

（一）创伤性事件

《精神障碍诊断和统计手册（第5版）》（Diagnostic and Statistical Manual of Mental Disorders，Fifth Edition，DSM-5）将创伤性事件（traumatic event，TE）定义为直接或间接经历到对生命造成的死亡性威胁，对身体造成的严重伤害、遭遇了性暴力。在我们每个人的一生中，都可能遇到各种各样的TE，不同的暴露类型在每个国家都不一样，而且TE的类型存在差异。女性比男性更容易暴露于性性质的TE，而男性更容易暴露于严重事故、袭击、战斗和灾难^［33］。当人们遭受重症创伤时，将会使其生理、行为以及心理发生变化，进而引起各种精神障碍。TE是导致PTSD及其相关精神心理障碍的直接原因，同时也是PTSD诊断的必要非充分条件^［34］。重症创伤患者在遭遇不同类型的TE后精神障碍的患病率是不同的，遭遇重大事故后患者精神障碍的患病率可高达60%^［5，7］，如交通事故、空难等。而在几类不同自然灾害后患者精神障碍的患病率为6%~80%^{［6，25，35］}，如地震、飓风等。

（二）患者因素

从种群来说：研究表明与白人相比，黑人退伍军人在创伤后PTSD的患病率较高^［36］；而白人抑郁症的患病率是非裔美国人的7倍^［37］。Roberts等^［38］的流行病数据表明，美国不同种族和民族的PTSD的患病率最高的是黑人（约8.7%），最低的是亚洲人（4%）。对于性别，男性和女性暴露TE的种类不一样，精神障碍的患病率不同，但在临床数据研究中当经历了相同TE后，与男性相比，女性患精神障碍的可能性更大，可能是性激素尤其是雌二醇和孕酮的潜在作用导致的^［39］。

（三）环境及医疗相关因素

对于遭受重症创伤事件前后患者处于的环境来说如存在或者有经历其他负性生活事件，如存在不良童年经历、离婚或丧偶、家境不好和身体健康状态欠佳等以上因素，可以增加精神障碍的患病率^{［40, 41］}。同时所处的医疗环境也可以增加创伤患者患精神障碍的可能性，如当患者在ICU接受治疗时由于各种因素如治疗时间过长、未能有效镇静或镇痛、行机械通气等，患者很容易出现精神障碍如ICU谵妄，对接受机械通气的危重症患者，急性谵妄的发生率高达80%^［42］。

四、重症创伤患者精神障碍可能的机制

（一）缺血反应

脑组织受到损害时导致脑血流减少、脑灌注不足引起脑代谢调节功能障碍及神经元变性、凋亡，如突触功能障碍、神经元障碍，诱发抑郁、焦虑等精神障碍。既往研究发现精神状态与缺血反应之间存在密切联系，Li等^［43］发现抑郁症患者额叶、颞叶、扣带回皮质的局部脑血流量下降。Yokota等^［44］通过分析发现谵妄患者额叶、颞叶等脑区血流量减少，当谵妄状态改善后脑血流量较强改善。

（二）神经递质失调

根据目前的相关研究显示，5-羟色胺（5-hydroxytryptamine，5-HT）、去甲肾上腺素（norepinephrine，NE）、多巴胺（dopamine，DA）、谷氨酸（glutamate，GLU）和γ-氨基丁酸（gamma-amino butyric acid，GABA）等相关神经递质可能是精神障碍的神经生物学机制中最重要的作用因素，上述神经递质水平的失调可能会引起重症创伤后相关神经障碍。大脑5-HT系统介导了脑内精神行为抑制系统，其功能紊乱可显著增强PTSD患者易激惹的临床症状，同时与紊乱的下丘脑垂体肾上腺素轴一起交互作用加剧患者的临床症状^［45］。临床上通过改变5-HT受体敏感性来提高5-HT含量进而改善抑郁症状^［46］；中枢NE从蓝斑核释放到前脑，在精神情绪活动上起着关键的调节作用，其功能障碍可能引起恐惧，增强唤醒和厌恶事件的记忆编码以及后来的再体验症状，进而导致PTSD等相关精神障碍^［47］；而DA也被认为是导致各种精神障碍的单胺类物质^{［48, 49］}；氨基酸类神经递质如GLU和GABA，在重症创伤应激状态下机体会自身额外分泌GABA并造成其累积，遗留的GABA可对组织造成损害，以及谷氨酸系统的功能障碍介导的神经毒性，导致PTSD等精神障碍的发生^［50］。

（三）炎症反应

近年来炎症假说受到了广泛的关注，该假说认为创伤应激刺激可以引起机体的炎症反应，并且通过一系列的机制最终导致相关精神障碍的产生。血液中常见炎性指标如C反应蛋白（C-reactive protein，CRP）、白介素（interleukin，IL）-1、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和干扰素-γ（interferon-γ，IFN-γ）等。首先创伤后精神障碍患者表现为机体炎症反应水平增高^［51］。精神障碍的炎症机制包括以下几个方面：（1）重症创伤后机体产生的促炎症因子可以直接导致神经元损伤；（2）促炎症因子通过促进体内氧化应激水平来发挥作用，研究表明抑郁症患者体内的氧化应激与炎症反应最终导致包括DNA在内的生物分子损伤增加^［52］；（3）炎症因子的过度表达可以通过引起下丘脑-垂体-肾上腺（hypothalamic-pituitary-adrenal，HPA）轴的过度激活、影响神经递质的浓度进而导致精神障碍的表现^［53］；（4）炎症介质通过对小胶质细胞异常刺激，又因为小胶质细胞是存在于中枢神经系统中的天然免疫细胞，可以吞噬清除受损的神经元，当其受到炎症介质的激活导致炎症级联反应时，可引起神经元的持续损伤^［54］。与此同时笔者也发现常见相关炎症信号通路异常激活导致创伤后精神障碍的产生，如NF-κB及2，3-二氧化吲哚胺（indoleamine 2，3 diacygenase，IDO）信号通路的激活等。

（四）HPA轴功能异常

HPA轴是神经内分泌系统的重要组成部分，参与控制机体的应激反应，维持内环境稳态，在人体应激反应中发挥着核心作用。HPA轴紊乱是焦虑症、抑郁症等精神障碍的共同发病机制^［55］。首先在激素水平变化：糖皮质激素（glucocorticoids，GCs）不仅能够促进新信息的获得与巩固，但可能同时也参与到恐惧记忆异常的巩固和储存，促进焦虑等精神障碍的发展^［56］。尽管部分研究显示PTSD患者皮质醇水平较健康对照升高，但大多数研究支持PTSD皮质醇分泌衰减的这一假说^［57］。同时高浓度的糖皮质激素对抑郁症的发展起促进作用^［46］。其次可见精神障碍患者糖皮质激素受体（glucocorticoid receptor，GR）的表达异常。Wang等^［58］研究发现抑制GR的表达可以导致产后抑郁症。

五、重症创伤患者精神障碍的防治

（一）预防性护理干预

重症创伤后导致的精神障碍一般是延迟性反应，所以预防性护理干预显得尤其重要。预防性的护理干预包括心理护理干预、安全和生活护理、康复护理干预等。心理护理干预是治疗精神障碍患者的重要辅助方法，帮助患者认识和正确对待致病因素和疾病性质，克服个性缺陷，掌握疾病康复途径，从而降低患者患精神障碍的风险，并提高其自我康复能力^［59］。心理干预疗法包括认知行为疗法（cognitive behavior therapy，CBT）、接受和承诺疗法、开放式对话疗法等。CBT是一种心理治疗手段，通过患者再次充分体验创伤情景，使患者在认知模拟和再现中得到支持鼓励，改善患者社会交往和人际关系，去战胜负性的心理认知，从而去达到治愈^［60］。van Dis等^［61］发现，CBT治疗焦虑相关障碍可以使焦虑症状水平显著下降。随着生物-心理-社会医学模式的改变，对不同精神障碍患者提供相应的心理干预是目前临床上重要的研究方向。

（二）环境改善及睡眠支持

社会环境中人际和谐关系是重症创伤后精神障碍出现的高度相关风险和保护因素。从社会人际关系角度去考虑，精神障碍治疗的成功机会可能会提高。医疗工作者可以通过加强或者重建精神障碍患者的社会支持系统，给患者提供安静舒适的环境，减少外部刺激等来帮助患者摆脱重症创伤带来的阴影，尽快缓解症状，从而提高自我康复的能力。在ICU中，响亮的声音和明亮的灯光等环境可以导致患者睡眠障碍，且睡眠障碍是造成重症创伤后患者相关精神障碍产生发展的危险因素^［62］。重症创伤后出现精神障碍的患者普遍存在睡眠障碍，且低质量的睡眠体验又会增加患者症状的严重性和后期症状的易感性^{［63, 64］}。Kamdar等^［65］研究发现通过改善睡眠质量可以减少ICU患者谵妄的发生率。所以采取干预措施通过减少环境噪声和光线等来减少夜间患者的不安，进而改善患者睡眠质量，降低精神障碍的发生率。

（三）药物治疗

重症创伤后患者的相关精神障碍表现有很多种，目前一般选择的是联合用药来改善症状、治疗共患病。选择性的5-HT再摄取抑制剂（selective serotonin reuptake inhibitors，SSRIs）包括帕罗西汀和舍曲林。SSRIs类药在应用于抗抑郁治疗的同时还可以改善患者PTSD的症状^［66］；5-HT与NE再摄取抑制剂（serotonin-norepinephrine reuptake inhibitor，SNRIs）通过阻滞NE和5-HT两种递质的再摄取来治疗PTSD、抑郁等精神障碍^［67］；抗焦虑药物中苯二氮䓬类抗焦虑药通过降低患者警觉程度来改善症状^［68］；其他药物如氯胺酮是N-甲基-D天门冬氨酸（N-methyl-D-aspartic acid，NMDA）受体非选择性拮抗剂，当以亚麻醉剂量给药时，能迅速减轻抑郁症状，2周内反复服用氯胺酮能显著减轻PTSD患者的症状^［69］。右美托咪定具有镇静、抗焦虑及轻度镇痛的作用。研究结果显示，右美托咪定是谵妄的保护性因素，能使谵妄的发生风险降低0.367倍^［70］（OR=0.367，95%CI：0.181~0.744）。因此医务工作者早期使用右美托咪定能有效降低重症创伤患者谵妄的发生率和缩短谵妄持续时间。

六、总结

重症创伤导致的相关精神障碍发病率较高，严重影响了患者的心理健康水平以及创伤的康复，对其进行及时的干预与救治显得尤为重要。近年来随着我国生物-心理-社会医学模式的转变，人们对创伤所致的精神障碍逐渐重视起来，临床上不断深化对重症创伤后相关精神障碍的认识。目前临床上缺乏重症创伤患者相关精神障碍的明确诊断标准，重症创伤相关精神障碍的特定诊断标准亟待探索；在治疗上，由于单纯药物治疗的效果不佳，心理干预联合药物治疗已成为目前治疗相关精神障碍的趋势，但还亟须进一步的临床研究去建立与探寻更有效的方案进行早期干预与治疗。

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