谵妄评估

简介

谵妄是指精神状态出现的急性波动性改变，伴有注意障碍、思维混乱和意识水平的改变。[1]Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73. http://www.ncbi.nlm.nih.gov/pubmed/10335730?tool=bestpractice.com 它是一种可能危及生命的病理状态，特点为高发病率和死亡率。 指南介绍了谵妄的识别、危险因素及治疗。[2]Devlin JW, Skrobik Y, Gélinas C, et al; American College of Critical Care Medicine. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-73. https://journals.lww.com/ccmjournal/Fulltext/2018/09000/Clinical_Practice_Guidelines_for_the_Prevention.29.aspx http://www.ncbi.nlm.nih.gov/pubmed/23269131?tool=bestpractice.com [3]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management in hospital and long-term care. Jan 2023 [internet publication]. https://www.nice.org.uk/guidance/cg103

后遗症

在医院内，经诊断伴发谵妄的患者死亡率是患有类似疾病但无谵妄患者的两倍，并且在诊断后一个月内死亡率最高可增加 14%。[4]Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ. 1993 Jul 1;149(1):41-6. http://www.ncbi.nlm.nih.gov/pubmed/8319153?tool=bestpractice.com 在美国，谵妄在住院病例中的发生率为每年 20% 至 25%，是最常见的住院相关并发症。[5]Brown TM, Boyle MF. Delirium. BMJ. 2002 Sep 21;325(7365):644-7. http://www.bmj.com/cgi/content/full/325/7365/644 http://www.ncbi.nlm.nih.gov/pubmed/12242179?tool=bestpractice.com [6]US Department of Health and Human Services. 2004 CMS Statistics. Washington, DC: Centers for Medicare and Medicaid Services, 2004:34. (CMS Publication No 03445) 谵妄在重症监护病房内较常见，尤其见于机械通气患者。对于危重患者，谵妄可导致住院时间延长及死亡率上升。[7]Cavallazzi R, Saad M, Marik PE. Delirium in the ICU: an overview. Ann Intensive Care. 2012 Dec 27;2(1):49. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539890 http://www.ncbi.nlm.nih.gov/pubmed/23270646?tool=bestpractice.com 研究显示，谵妄在急诊科老年患者中的患病率为 12%。[8]Han JH, Wilson A, Vasilevskis EE, et al. Diagnosing delirium in older emergency department patients: validity and reliability of the delirium triage screen and the brief confusion assessment method. Ann Emerg Med. 2013 Nov;62(5):457-65. http://www.ncbi.nlm.nih.gov/pubmed/23916018?tool=bestpractice.com 然而尽管患者经常出现谵妄，但由于谵妄症状的波动性以及医护人员缺乏足够的重视，因此谵妄经常被忽视。 谵妄还会导致躯体功能和认知能力下降、康复治疗预后不佳、被收容照看以及重新入院接受治疗的风险增加。[1]Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73. http://www.ncbi.nlm.nih.gov/pubmed/10335730?tool=bestpractice.com [9]Kiely DK, Bergmann MA, Murphy KM, et al. Delirium among newly admitted postacute facility patients: prevalence, symptoms, and severity. J Gerontol A Biol Sci Med Sci. 2003 May;58(5):441-5. http://www.ncbi.nlm.nih.gov/pubmed/12730254?tool=bestpractice.com [10]Murray AM, Levkoff SE, Wetle T, et al. Acute delirium and functional decline in the hospitalized elderly patient. J Gerontol. 1993 Sep;48(5):M181-6. http://www.ncbi.nlm.nih.gov/pubmed/8366260?tool=bestpractice.com [11]Marcantonio ER, Simon SE, Bergmann MA, et al. Delirium symptoms in post-acute care: prevalent, persistent, and associated with poor functional recovery. J Am Geriatr Soc. 2003 Jan;51(1):4-9. http://www.ncbi.nlm.nih.gov/pubmed/12534838?tool=bestpractice.com [12]van den Boogaard M, Schoonhoven L, Evers AW, et al. Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med. 2012 Jan;40(1):112-8. http://www.ncbi.nlm.nih.gov/pubmed/21926597?tool=bestpractice.com 尽管一般认为谵妄是可逆的，但研究显示，谵妄症状在发作后可持续数周至数月。[13]Roche V. Southwestern Internal Medicine Conference. Etiology and management of delirium. Am J Med Sci. 2003 Jan;325(1):20-30. http://www.ncbi.nlm.nih.gov/pubmed/12544081?tool=bestpractice.com 老年住院患者常出现持续性谵妄，并且与不良预后有关。[14]Cole MG, Ciampi A, Belzile E, et al. Persistent delirium in older hospital patients: a systematic review of frequency and prognosis. Age Ageing. 2009 Jan;38(1):19-26. http://ageing.oxfordjournals.org/content/38/1/19.long http://www.ncbi.nlm.nih.gov/pubmed/19017678?tool=bestpractice.com

分类

精神疾病诊断与统计手册（DSM-5-TR）指出，患者必须表现出以下全部 4 项特征才能被诊断为谵妄。[15]American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022

1. 注意力障碍（即对环境的认识清晰度下降）明显，伴集中、保持或转移注意力的能力下降。 这种意识障碍可能较轻微，最初仅表现为昏睡或注意力分散，临床医生和/或家人常常会认为其与原发性疾病有关而不予重视。

2. 认知改变（例如，记忆缺失、定向障碍、语言障碍）或出现之前存在或目前存在的痴呆无法解释的知觉障碍。

3. 这种障碍在短期内（通常为数小时至数日）出现，表现为急性起病，一天当中症状往往会出现波动。

4. 来自病史、体格检查或实验室检测结果的证据表明，这种障碍由全身疾病状态、物质中毒或物质戒断直接导致。 注意力和认知的改变不应发生在觉醒水平严重降低（例如，昏迷）的情况下。

目前谵妄一般分为三种临床亚型。[16]Potter J, George J; Guideline Development Group. The prevention, diagnosis and management of delirium in older people: concise guidelines. Clin Med. 2006 May-Jun;6(3):303-8. http://www.ncbi.nlm.nih.gov/pubmed/16826866?tool=bestpractice.com [17]Gupta N, de Jonghe J, Schieveld J, et al. Delirium phenomenology: what can we learn from the symptoms of delirium? J Psychosom Res. 2008 Sep;65(3):215-22. http://www.ncbi.nlm.nih.gov/pubmed/18707943?tool=bestpractice.com [18]Meagher DJ, Leonard M, Donnelly S, et al. A longitudinal study of motor subtypes in delirium: frequency and stability during episodes. J Psychosom Res. 2012 Mar;72(3):236-41. http://www.ncbi.nlm.nih.gov/pubmed/22325705?tool=bestpractice.com 其中包括：

1. 活动过度型谵妄 — 该型患者一般处于高度觉醒状态，并伴有坐立不安、激越、幻觉和不适当行为

2. 活动减退型谵妄 — 该型患者一般具有昏睡、肢体活动减少、语无伦次和缺乏兴趣的表现

3. 混合型谵妄 — 同时具有活动过度型和活动减退型的体征和症状。

术语“亚综合征谵妄”是指部分消退或不完整形式的谵妄。

流行病学

谵妄在社区中的患病率预计为 1% 至 2%；对于年龄在 85 岁以上的患者，这一数字则上升至 14%。[13]Roche V. Southwestern Internal Medicine Conference. Etiology and management of delirium. Am J Med Sci. 2003 Jan;325(1):20-30. http://www.ncbi.nlm.nih.gov/pubmed/12544081?tool=bestpractice.com

老年住院患者的谵妄患病率为 10%-40%。[5]Brown TM, Boyle MF. Delirium. BMJ. 2002 Sep 21;325(7365):644-7. http://www.bmj.com/cgi/content/full/325/7365/644 http://www.ncbi.nlm.nih.gov/pubmed/12242179?tool=bestpractice.com

在内科病患中，谵妄的患病率高达 30%。[3]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management in hospital and long-term care. Jan 2023 [internet publication]. https://www.nice.org.uk/guidance/cg103 急诊科患者的患病率为 14%-24%，术后患者的为 15%-53%，重症监护患者的为 70%- 87%。[19]Inouye SK. Delirium in hospitalized older patients. Clin Geriatr Med. 1998 Nov;14(4):745-64. http://www.ncbi.nlm.nih.gov/pubmed/9799477?tool=bestpractice.com [20]Pisani MA, McNicoll L, Inouye SK. Cognitive impairment in the intensive care unit. Clin Chest Med. 2003 Dec;24(2):727-37. http://www.ncbi.nlm.nih.gov/pubmed/14710700?tool=bestpractice.com [21]Neufeld KJ, Thomas C. Delirium: definition, epidemiology, and diagnosis. J Clin Neurophysiol. 2013 Oct;30(5):438-42. http://www.ncbi.nlm.nih.gov/pubmed/24084176?tool=bestpractice.com

病理生理学

• 谵妄的病理生理机制尚不明确。 神经影像学研究显示存在脑部多个不相关区域功能障碍，这些区域包括前额叶、皮层下结构、丘脑、基底神经节、舌回、梭状回和颞顶皮层。[22]Singer GG, Brenner BM. Fluid and electrolyte disturbances. In: Kasper DL, Fauci AS, Longo DL, et al. eds. Harrison's Principles of Internal Medicine, 16th ed. New York, NY: McGraw Hill; 2005:252-63.[23]Choi SH, Lee H, Chung TS, et al. Neural network functional connectivity during and after an episode of delirium. Am J Psychiatry. 2012 May;169(5):498-507. http://www.ncbi.nlm.nih.gov/pubmed/22549209?tool=bestpractice.com

• 脑电图 (EEG) 研究结果也表明皮层活动弥漫性放缓。

• 谵妄发病也与神经递质、炎症和慢性应激有关。 例如，使用抗胆碱能药物的患者谵妄发生率显著增高，表明胆碱能神经递质缺乏与谵妄发生有关。[24]Trzepacz P, van der Mast R. The neuropathophysiology of delirium. In: Lindesay J, Rockwood K, Macdonald A, eds. Delirium in old age. Oxford, UK: Oxford University Press; 2002:51-90. 针对手术患者的研究已证实术后发生谵妄的患者体内胆碱能系统与免疫系统之间存在互动功能障碍。[25]Cerejeira J, Nogueira V, Luís P, et al. The cholinergic system and inflammation: common pathways in delirium pathophysiology. J Am Geriatr Soc. 2012 Apr;60(4):669-75. http://www.ncbi.nlm.nih.gov/pubmed/22316182?tool=bestpractice.com

• 多巴胺能过剩也被认为会引起谵妄。证据似乎并不支持使用抗精神病药物（多巴胺受体拮抗剂）来预防或治疗谵妄，但证据不完全一致。[26]Oh ES, Needham DM, Nikooie R, et al. Antipsychotics for preventing delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019 Oct 1;171(7):474-84. https://www.doi.org/10.7326/M19-1859 http://www.ncbi.nlm.nih.gov/pubmed/31476766?tool=bestpractice.com [27]Janssen TL, Alberts AR, Hooft L, et al. Prevention of postoperative delirium in elderly patients planned for elective surgery: systematic review and meta-analysis. Clin Interv Aging. 2019;14:1095-117. https://www.doi.org/10.2147/CIA.S201323 http://www.ncbi.nlm.nih.gov/pubmed/31354253?tool=bestpractice.com [28]Siddiqi N, Harrison JK, Clegg A, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2016 Mar 11;3:CD005563. https://www.doi.org/10.1002/14651858.CD005563.pub3 http://www.ncbi.nlm.nih.gov/pubmed/26967259?tool=bestpractice.com [29]Nikooie R, Neufeld KJ, Oh ES, et al. Antipsychotics for treating delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019 Oct 1;171(7):485-95. https://www.doi.org/10.7326/M19-1860 http://www.ncbi.nlm.nih.gov/pubmed/31476770?tool=bestpractice.com [30]Zayed Y, Barbarawi M, Kheiri B, et al. Haloperidol for the management of delirium in adult intensive care unit patients: a systematic review and meta-analysis of randomized controlled trials. J Crit Care. 2019 Apr;50:280-6. https://www.doi.org/10.1016/j.jcrc.2019.01.009 http://www.ncbi.nlm.nih.gov/pubmed/30665181?tool=bestpractice.com [31]Burry L, Hutton B, Williamson DR, et al. Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev. 2019 Sep 3;9:CD011749. https://www.doi.org/10.1002/14651858.CD011749.pub2 http://www.ncbi.nlm.nih.gov/pubmed/31479532?tool=bestpractice.com [32]Kishi T, Hirota T, Matsunaga S, et al. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2016 Jul;87(7):767-74. https://www.doi.org/10.1136/jnnp-2015-311049 http://www.ncbi.nlm.nih.gov/pubmed/26341326?tool=bestpractice.com [33]Finucane AM, Jones L, Leurent B, et al. Drug therapy for delirium in terminally ill adults. Cochrane Database Syst Rev. 2020 Jan 21;1(1):CD004770. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984445 http://www.ncbi.nlm.nih.gov/pubmed/31960954?tool=bestpractice.com ​

• 涉及谵妄病理生理学的其他神经递质包括去甲肾上腺素、5-羟色胺、γ-氨基丁酸、谷氨酸和褪黑素。

• 另有证据表明白细胞介素 1 和 2、TNF-α 和干扰素等细胞因子也与谵妄的发生相关。[34]Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. The immunology of delirium. Neuroimmunomodulation. 2014;21(2-3):72-8. http://www.ncbi.nlm.nih.gov/pubmed/24557038?tool=bestpractice.com

• 此外，继发于疾病或外伤的慢性应激所诱发的慢性皮质醇增多症也可能会导致谵妄。[35]Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. http://www.ncbi.nlm.nih.gov/pubmed/16540616?tool=bestpractice.com