今日の臨床サポート

せん妄

著者: 中村純 産業医科大学 名誉教授

監修: 上島国利 昭和大学

著者校正/監修レビュー済:2021/03/17
参考ガイドライン:
  1. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Delirium:prevention, diagnosis and management. Clinical guideline [CG103](2010)
  1. Delirium:Evidence Update April 2012:A summary of selected new evidence relevant to NICE clinical guideline 103 ‘Delirium: diagnosis, prevention and management’(2010)
  1. 日本総合病院精神医学会せん妄指針改訂班編:せん妄の臨床指針〔せん妄の治療指針 第2版〕(2015)
  1. 日本集中治療学会J-PADガイドライン作成委員会:日本版・集中治療室における成人重症患者に対する痛み・不穏・せん妄管理のための臨床ガイドライン(2014)
患者向け説明資料

概要・推奨   

  1. せん妄の治療は、薬物療法の前に不安の軽減などの心理的な介入のほか環境調整(積極的な離床、運動療法)などを発症予防のために行うことが重要である
  1. ハロペリドールとクロルプロマジンとではせん妄に対する効果に差はない(推奨度2)
  1. リスペリドンは、せん妄に対して平均1.7mgで数日以内にせん妄に効果を示す(推奨度2)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
中村純 : 特に申告事項無し[2021年]
監修:上島国利 : 原稿料(大日本住友製薬)[2021年]

改訂のポイント:
  1. 定期レビューを行い、せん妄の発症予防及び治療に関する新しいネットワークメタアナリシスの文献を追記した。 

病態・疫学・診察

疫学情報・病態・注意事項  
  1. せん妄は、錯覚・幻覚(幻視・幻聴)などの異常体験、精神運動興奮・不安などが加わった特殊な意識障害である。
  1. せん妄の有病率は、入院患者の10~30%、高齢者では10~40%に起こる。入院している癌患者では25%、入院しているエイズ患者では30~40%、術後患者の51%、末期患者の約80%に臨死期に発症するとされている[1][2][3]
  1. 身体疾患を有する男性の高齢者に多く発症するため、基礎となる身体疾患の回復を遅らせたり、その治療に支障を来すことがある。
  1. 認知症に重畳したせん妄、夜間せん妄、術後せん妄、ICU症候群、CCU症候群、アルコール依存症離脱時に発症する振せんせん妄などさまざまな名前が付けられているが、病態の本質は同一と考えられ、睡眠・覚醒リズムの障害が背景にあると考えられる。
  1. したがって、治療及び発症の予防には原疾患の治療および環境調整、身体的、心理的な介入などの非薬物療法に加えて、薬物よる睡眠・覚醒リズムを整えることを目標にする。
 
  1. せん妄の原因疾患
  1. 特定の精神疾患、身体疾患がその原因となるわけではなく、その本質と考えられる睡眠・覚醒リズムを乱すあらゆる状態がせん妄の原因になり得る。したがって、治療を有するような疾患でなくても、痒みや痛みなど睡眠を阻害するような要因があるだけでせん妄が発症することもある。しかし、認知症など脳に器質性の変化があるものでは、せん妄が発症しやすい。
 
せん妄発症の原因

せん妄の発症因子は、直接因子、誘発因子、準備因子に分けられる。

 
  1. 神経画像研究
  1. 神経画像研究では、大脳皮質萎縮や脳室が拡大している人にせん妄が発症しやすいという報告がある[4]
 
  1. 疫学的情報1(推奨度1)[5][6][7][8]
  1. あらゆる身体疾患、高齢者、男性、術後などでせん妄は発症する。
  1. 術後、ICU、CCUなどの環境要因、脳器質性疾患の存在、高齢者などが誘因になる。
 
  1. 疫学的情報2:整形外科領域でのせん妄患者を対象にした研究(推奨度2)[9]
  1. せん妄を伴う患者の中で特に整形外科的手術後、せん妄患者は術後合併症、術後回復の長期化、すなわち入院の長期化、機能障害の長期化の危険性が高い。
 
  1. 疫学的情報3:せん妄は高齢者、入院患者、合併症がある人などで発症する(推奨度2)[10][11][12]
  1. せん妄が発症すると入院は長期化し、認知機能だけでなく身体的な機能障害も長期化、悪化する人が多い。
  1. 追記:入院患者にせん妄が発症すると入院が長期化し、退院後の予後も悪い。退院後、6カ月後以内に死亡するせん妄既往患者は約25%に達し、診断後3カ月以内の死亡率は感情障害患者の約14倍あることを示す報告もある。
 
  1. 疫学的情報4:認知機能の低下はせん妄の遷延化と関係している。
  1. 集中治療室で呼吸不全またはショック状態の成人821人を対象に認知障害を検討した[13]。入院中の患者74%にせん妄が発症していた。せん妄の遷延化は、3カ月と12カ月時の全般的な認知機能スコアの悪化および実行機能スコアの悪化と独立して関連していた。
 
診断、治療のガイドライン:
  1. せん妄の診断、治療のガイドラインとしては、以下の3つがあるが、一番新しい米国のガイドラインも2013年のものが最新版である。
  1. 米国のガイドライン:
  1. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit.[14]
  1. 英国のガイドライン:
  1. Delirium:Diagnosis, prevention and management, 2010[15]
  1. Delirium:Evidence Update April 2012[16]
  1. 日本のガイドライン:
  1. せん妄の治療指針 第2版(2015)[17]
  1. 日本集中治療学会J-PADガイドライン作成委員会:日本版・集中治療室における成人重症患者に対する痛み・不穏・せん妄管理のための臨床ガイドライン(2014)[18]
  1. 米国クリティカルケア医学会(American College of Critical Care Medicine)による疼痛、不穏、せん妄の管理のための臨床実践ガイドラインは、ICUでの疼痛、不穏の管理を含むガイドラインで、せん妄に特化したものではないが、米国の複数の医学団体が合同で作成したものである。
  1. 米国のICUのガイドラインで高く評価されたせん妄ケア
  1. 1. せん妄のモニタリング
  1. 2. 早期に動かすこと(早期離床、リハビリテーションなど)
  1. 3. 鎮静薬の定期使用の場合、日中は投与中断するか軽度鎮静管理
  1. 4. 多職種チームアプローチ(教育研修、プロトコル、チェックのためのラウンドなど)
  1. 英国のガイドラインの特徴
  1. リスクファクターの評価:
  1. ①65歳以上、②認知症や過去のエピソードを含めた認知機能の低下(認知機能評価スケールを用いること)、 ③大腿骨骨折、④重篤な基礎疾患の有無、の4つを挙げている。
  1. 早期徴候の把握:
  1. ①数時間・数日間の行動の変化や動揺を見逃さないこと、②集中困難・反応遷延・混乱といった症状で現れる低活動型せん妄を見逃さないこと、③必要な処置への非協力などもせん妄の予兆の可能性があること、などを強調。
  1. 予防:
  1. よく訓練された多職種が提供するケアパッケージにより、入眠24時間以内にせん妄危険因子をもつハイリスク者を同定し、アセスメントに基づき、危険因子を是正し、認知機能低下、感覚遮断、不動化、不眠、多剤処方、低栄養、疼痛を標的とした非薬物療法を提供することを推奨している。
問診・診察のポイント  
  1. 手術後、ICUやCCU搬入後、あるいはアルコール依存症者が断酒したのち、または認知症患者が急に落ち着かなくなり、会話がまとまらず、幻視などの異常体験を訴え興奮するなど精神病状態が急に発症したときにせん妄を疑う。

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文献 

FDA.
著者: Z J Lipowski
雑誌名: JAMA. 1987 Oct 2;258(13):1789-92.
Abstract/Text Delirium (acute confusional states), a common and often overlooked psychiatric disorder, can occur at any age, but elderly persons are especially prone to develop it. In later life, it is often a conspicuous feature of systemic or cerebral disease and drug (notably anticholinergic) toxicity, and it may constitute a grave prognostic sign. Its development in a hospitalized patient may interfere with his or her management, disrupt ward routine, and cause medicolegal complications as a result of patient injury. Acute onset of a fluctuating level of awareness, accompanied by sleep-wake cycle disruption, lethargy or agitation, and nocturnal worsening of symptoms, are diagnostic. Early recognition of delirium and treatment of its underlying cause are essential.

PMID 3625989  JAMA. 1987 Oct 2;258(13):1789-92.
著者: F Stiefel, J Holland
雑誌名: Int Psychogeriatr. 1991 Winter;3(2):333-6.
Abstract/Text Delirium is the second most common psychiatric diagnosis among hospitalized elderly cancer patients. A variety of factors are known to cause delirium in cancer patients, and the most frequently observed are outlined. History, presence of an altered mental state with identification of the cognitive impairment, and a close watch of mental function will help to differentiate delirium from a normal stress reaction, an adjustment disorder to cancer diagnosis, or early dementia. As in other medically ill patients, antipsychotic drugs are the cornerstone of treatment for delirium not manageable with environmental manipulation or causal therapy. Haloperidol is the most commonly prescribed drug for delirium in the cancer setting because of its low cardiovascular and anticholinergic effects. Cancer patients who are debilitated require a much lower starting dose than do the physically healthy.

PMID 1811785  Int Psychogeriatr. 1991 Winter;3(2):333-6.
著者: S W Perry
雑誌名: Am J Psychiatry. 1990 Jun;147(6):696-710.
Abstract/Text HIV directly affects the CNS, primarily causing subcortical neuropathology. Dementia as the initial presentation is rare, but organic mental changes that mimic many functional disorders can occur during the course of infection. The mental status examination is not adequately sensitive to detect noncognitive dysfunction, and subjective complaints, neurological signs, reduced T4 lymphocytes, CSF abnormalities, diffuse slowing on ECG, mild cerebral atrophy on brain CT, and nonspecific hyperdensities on brain magnetic resonance imaging do not correlate reliably with early and subtle HIV-induced neuropsychological impairment. Zidovudine (AZT) can delay or reverse mental deficits, and psychostimulants can reduce apathetic withdrawal, but high-potency neuroleptics can cause neuroleptic malignant syndrome.

PMID 2188514  Am J Psychiatry. 1990 Jun;147(6):696-710.
著者: Dimitrios Adamis, Chantal J Slor, Maeve Leonard, Joost Witlox, Jos F M de Jonghe, Alastair J D Macdonald, Paula Trzepacz, David Meagher
雑誌名: J Psychiatr Res. 2013 Jul;47(7):966-71. doi: 10.1016/j.jpsychires.2013.02.012. Epub 2013 Mar 21.
Abstract/Text Delirium's characteristic fluctuation in symptom severity complicates the assessment of test-retest reliability of scales using classical analyses, but application of modelling to longitudinal data offers a new approach. We evaluated test-retest reliability of the delirium rating scale (DRS) and delirium rating scale-revised-98 (DRS-R98), two widely used instruments with high validity and inter-rater reliability. Two existing longitudinal datasets for each scale included DSM-IV criteria for delirium diagnosis and repeated measurements using the DRS or DRS-R98. To estimate the reliability coefficients RT and RΛ for each scale we used a macros provided by Dr. Laenen at http://www.ibiostat.be/software/measurement.asp. For each dataset a linear mixed-effects model was fitted to estimate the variance-covariance parameters. A total of 531 cases with between 4 and 9 measurement points across studies including both delirious and non-delirious patients. Comorbid dementia in the datasets varied from 27% to 55%. Overall RT for the DRS were 0.71 and 0.50 and for DRS-R98 0.75 and 0.84. RΛ values for DRS were 0.99 and 0.98 and for DRS-R98 were 0.92 and 0.96. Individual RT measures for DRS-R98 and DRS across visits within studies showed more range than overall values. Our models found high overall reliability for both scales. Multiple factors impact a scale's reliability values including sample size, repeated measurements, patient population, etc in addition to rater variability.

Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID 23522935  J Psychiatr Res. 2013 Jul;47(7):966-71. doi: 10.1016/j.・・・
著者: M P Rogers, M H Liang, L H Daltroy, H Eaton, J Peteet, E Wright, M Albert
雑誌名: Int J Psychiatry Med. 1989;19(2):109-21.
Abstract/Text Forty-six orthopedic patients were studied to determine the incidence, natural history, and risk factors associated with post-operative delirium. Pre-operatively, patients were given a neuropsychological screening evaluation, the Mood Adjective Checklist (MACL), the Zung Depression Scale, the Anxiety Inventory Scale, and the Health Assessment Questionnaire (HAQ). A psychiatrist interviewed each patient on post-op day four for evidence of delirium as defined by DSM III criteria. Of the patients studied, thirteen (26%) were possibly or definitely delirious following surgery. Treatment with propranolol, scopolamine, or flurazepam (Dalmane) conferred a relative risk for delirium of 11.7 (p = 0.0028). Delirium was associated with increased post-operative complications (p = 0.01), poorer post-operative mood (p = 0.06), and an increase of about 1.5 days in length of stay (not significant). Delirious patients were significantly less likely than matched controls to improve in function at six months compared with a pre-operative baseline HAQ (t = 6.43, p less than 0.001).

PMID 2807736  Int J Psychiatry Med. 1989;19(2):109-21.
著者: M G Cole, F J Primeau
雑誌名: CMAJ. 1993 Jul 1;149(1):41-6.
Abstract/Text OBJECTIVE: To determine the prognosis of delirium in elderly patients.
DATA SOURCES: MEDLINE was searched for relevant articles published from January 1980 to March 1992. The bibliographies of identified articles were searched for additional references.
STUDY SELECTION: Eight reports (involving 573 patients with delirium) met the following inclusion criteria: original research, published in English or French, prospective study design, diagnosis based on acute deterioration in mental state, sample of at least 20 patients, patients aged 60 years or over and follow-up of at least 1 week. The validity of the studies was independently assessed according to the criteria for prognostic studies established by McMaster University, Hamilton, Ont. No study met all the criteria.
DATA EXTRACTION: Information about the patient sample, length of follow-up and results was systematically abstracted from each report and tabulated.
DATA SYNTHESIS: A meta-analysis of the outcomes indicated that elderly patients with delirium had a mean length of stay of 20.7 days. One month after admission 46.5% were in institutions, and 14.2% had died; only 54.9% had improved mentally. Six months after admission 43.2% were in institutions. Compared with unmatched control subjects they had longer hospital stays, higher mortality rates at 1 month and higher rates of institutional care at 1 and 6 months. The presence of severe physical illness or dementia may have been related to some outcomes.
CONCLUSIONS: Delirium in the elderly appears to have a poor prognosis. However, this finding may have been confounded by the presence of concomitant dementia or severe physical illness. Future studies must pay attention to methods and design, particularly the composition of study populations and the control of extraneous prognostic factors.

PMID 8319153  CMAJ. 1993 Jul 1;149(1):41-6.
著者: P T Trzepacz, G B Teague, Z J Lipowski
雑誌名: Gen Hosp Psychiatry. 1985 Apr;7(2):101-6.
Abstract/Text The authors analyze 133 cases of organic mental disorders (OMDs) from a total of 771 patients who were referred for psychiatric consultation from a general hospital. The cases represent a 2-year referral period which began July 1, 1980, when DSM-III criteria were instituted. Delirium and dementia are most commonly diagnosed and features of these, particularly in the geriatric population, are described. Delirium was more frequent in patients with multiple medical problems, was an indicator of poor prognosis having the highest mortality rate, and was usually undiagnosed by the referring physician.

PMID 3996899  Gen Hosp Psychiatry. 1985 Apr;7(2):101-6.
著者: P P Pandharipande, T D Girard, J C Jackson, A Morandi, J L Thompson, B T Pun, N E Brummel, C G Hughes, E E Vasilevskis, A K Shintani, K G Moons, S K Geevarghese, A Canonico, R O Hopkins, G R Bernard, R S Dittus, E W Ely, BRAIN-ICU Study Investigators
雑誌名: N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/NEJMoa1301372.
Abstract/Text BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized.
METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders.
RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months.
CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

PMID 24088092  N Engl J Med. 2013 Oct 3;369(14):1306-16. doi: 10.1056/・・・
著者: Juliana Barr, Gilles L Fraser, Kathleen Puntillo, E Wesley Ely, Céline Gélinas, Joseph F Dasta, Judy E Davidson, John W Devlin, John P Kress, Aaron M Joffe, Douglas B Coursin, Daniel L Herr, Avery Tung, Bryce R H Robinson, Dorrie K Fontaine, Michael A Ramsay, Richard R Riker, Curtis N Sessler, Brenda Pun, Yoanna Skrobik, Roman Jaeschke, American College of Critical Care Medicine
雑誌名: Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72.
Abstract/Text OBJECTIVE: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002.
METHODS: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding.
CONCLUSION: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

PMID 23269131  Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM・・・
著者: Lu-Xi Deng, Lan Cao, Li-Na Zhang, Xiao-Bei Peng, Lei Zhang
雑誌名: J Crit Care. 2020 Aug 31;60:241-248. doi: 10.1016/j.jcrc.2020.08.019. Epub 2020 Aug 31.
Abstract/Text OBJECTIVE: To compare non-pharmacological interventions in their ability to prevent delirium in critically ill patients, and find the optimal regimen for treatment.
METHODS: Literature searches were conducted using PubMed, Embase, CINAHL, and Cochrane Library databases until the end of June 2019. We estimated the risk ratios (RRs) for the incidence of delirium and in-hospital mortality and found the mean difference (MD) for delirium duration and the length of ICU stay. The probabilities of interventions were ranked based on clinical outcomes. The study was registered on PROSPERO (CRD42020160757).
RESULTS: Twenty-six eligible studies were included in the network meta-analysis. Studies were grouped into seven intervention types: physical environment intervention (PEI), sedation reducing (SR), family participation (FP), exercise program (EP), cerebral hemodynamics improving (CHI), multi-component studies (MLT) and usual care (UC). In term of reducing the incidence of delirium, the two most effective interventions were FP (risk ratio (RR) 0.19, 95% confidence interval (CI) 0.08 to 0.44; surface under the cumulative ranking curve (SUCRA) = 94%) and MLT (RR 0.43, 95% CI 0.30 to 0.57; SUCRA = 68%) compared with observation. Although all interventions demonstrated nonsignificant efficacy in regards to delirium duration and the length of the patient's stay in the ICU, MLT (SUCRA = 78.6% and 71.2%, respectively) was found to be the most effective intervention strategy. In addition, EP (SUCRA = 97.2%) facilitated a significant reduction in hospital mortality, followed in efficacy by MLT (SUCRA = 73.2%), CHI (SUCRA = 35.8%), PEI (SUCRA = 34.8%), and SR (SUCRA = 31.8%).
CONCLUSIONS: Multi-component strategies are overall the optimal intervention techniques for preventing delirium and reducing ICU length of stay in critically ill patients by way of utilizing several interventions simultaneously. Additionally, family participation as a method of patient-centered care resulted in better outcomes for reducing the incidence of delirium.

Copyright © 2020 Elsevier Inc. All rights reserved.
PMID 32919363  J Crit Care. 2020 Aug 31;60:241-248. doi: 10.1016/j.jcr・・・
著者: William Breitbart, Christopher Gibson, Annie Tremblay
雑誌名: Psychosomatics. 2002 May-Jun;43(3):183-94. doi: 10.1176/appi.psy.43.3.183.
Abstract/Text We conducted a systematic examination of the experience of delirium in a sample of 154 hospitalized patients with cancer. Patients all met DSM-IV criteria for delirium and were rated with the Memorial Delirium Assessment Scale as a measure of delirium severity, phenomenology, and resolution. Of the 154 patients assessed, 101 had complete resolution of their delirium and were administered the Delirium Experience Questionnaire (DEQ-a face-valid measure that assesses delirium recall and distress related to the delirium episode). Spouse/caregivers and primary nurses were also administered the DEQ to assess distress related to caring for a delirious patient. Fifty-four (53.5%) patients recalled their delirium experience. Logistic-regression analysis demonstrated that short-term memory impairment (odds ratio [OR] = 38.4), delirium severity (OR = 11.3), and the presence of perceptual disturbances (OR = 6.9) were significant predictors of delirium recall. Mean delirium-related distress levels (on a 0-4 numerical rating scale of the DEQ) were 3.2 for patients who recalled delirium, 3.75 for spouses/caregivers, and 3.09 for nurses. Logistic-regression analysis demonstrated that the presence of delusions (OR = 7.9) was the most significant predictor of patient distress. Patients with "hypoactive" delirium were just as distressed as patients with "hyperactive" delirium. Karnofsky Performance Status (OR = 9.1) was the most significant predictor of spouse/caregiver distress. Delirium severity (OR =5.2) and the presence of perceptual disturbances (OR =3.6) were the most significant predictors of nurse distress. In conclusion, a majority of patients with delirium recall their delirium as highly distressing. Delirium is also a highly distressing experience for spouses/caregivers and nurses who are caring for delirious patients. Prompt recognition and treatment of delirium is critically important to reduce suffering and distress.

PMID 12075033  Psychosomatics. 2002 May-Jun;43(3):183-94. doi: 10.1176・・・
著者: Chang-Su Han, Yong-Ku Kim
雑誌名: Psychosomatics. 2004 Jul-Aug;45(4):297-301. doi: 10.1016/S0033-3182(04)70170-X.
Abstract/Text To compare the clinical efficacy of haloperidol and risperidone for the treatment of delirium, the authors performed a double-blind comparative study. Twenty-eight patients with delirium were recruited and randomly assigned to receive a flexible-dose regimen of haloperidol or risperidone over 7 days. The severity of delirium was assessed by using Memorial Delirium Assessment Scale scores. Scores for each group decreased significantly over the study period. However, no significant differences in mean Memorial Delirium Assessment Scale scores between groups were found. The group-by-time effect was not significant. In addition, there was no significant difference in the frequency of response to the drugs between the two groups. One patient in the haloperidol group experienced mild akathisia, but no other patients reported clinically significant side effects. These data show no significant difference in the efficacy or response rate between haloperidol and risperidone in the treatment of delirium.

PMID 15232043  Psychosomatics. 2004 Jul-Aug;45(4):297-301. doi: 10.101・・・
著者: Eduard Parellada, Inmaculada Baeza, Joan de Pablo, Guadalupe Martínez
雑誌名: J Clin Psychiatry. 2004 Mar;65(3):348-53.
Abstract/Text BACKGROUND: The aim of this study was to evaluate the efficacy and safety of risperidone in the treatment of patients with delirium.
METHOD: We conducted a prospective, multicenter, observational 7-day study in 5 university general hospitals. Sixty-four patients (62.5% male [N = 40]; mean age: 67.3 +/- 11.4 years) hospitalized due to a medical condition who met criteria for delirium according to DSM-IV were enrolled in the study. Fifty-six patients received 7 days of treatment or less, while 8 patients continued treatment for more than 7 days. Effectiveness was assessed using the Trzepacz Delirium Rating Scale (DRS), the positive subscale of the PANSS (PANSS-P), the Mini-Mental State Examination (MMSE), and the Clinical Global Impressions scale (CGI). Safety assessment included the UKU Side Effect Rating Scale. Risperidone was administered at the time of diagnosis, and treatment was maintained according to clinical response. Response to treatment was defined as a reduction in DRS score to below 13 within the first 72 hours. Data were gathered from April to December 2000.
RESULTS: Risperidone (mean dose = 2.6 +/- 1.7 mg/day at day 3) was effective in 90.6% (58/64) of the patients and significantly improved all symptoms measured by the scales from baseline to day 7 (mean scores: DRS, 22.5 +/- 4.6 at baseline to 6.8 +/- 7.0 at day 7; PANSS-P, 21.5 +/- 8.8 to 10.1 +/- 7.3; MMSE, 13.1 +/- 10.9 to 26.4 +/- 8.9; and CGI, 4.5 +/- 0.9 to 1.9 +/- 1.2) (Friedman test, p <.001 in all cases). Two patients (3.1%) experienced adverse events, but none showed extrapyramidal symptoms.
CONCLUSIONS: Low-dose risperidone proved to be a safe and effective drug in the treatment of symptoms of delirium in medically hospitalized patients. These data provide the rationale for a prospective randomized controlled trial.

PMID 15096074  J Clin Psychiatry. 2004 Mar;65(3):348-53.
著者: Naoshi Horikawa, Tomoko Yamazaki, Kazuko Miyamoto, Akiko Kurosawa, Hiroaki Oiso, Fumi Matsumoto, Katsuji Nishimura, Kumiko Karasawa, Kiyoshi Takamatsu
雑誌名: Gen Hosp Psychiatry. 2003 Jul-Aug;25(4):289-92.
Abstract/Text Delirium is a common psychiatric illness among medically compromised patients. There is an increasing opportunity to use atypical antipsychotics to treat delirium. The effects of these drugs on delirium, however, the most appropriate way to use them, and the associated adverse effects remain unclear. To clarify these points, a prospective open trial on risperidone was carried out in 10 patients with delirium. At a low dose of 1.7 mg/d, on average, risperidone was effective in 80% of patients, and the effect appeared within a few days. There were no serious adverse effects. However, sleepiness (30%) and mild drug-induced parkinsonism (10%) were observed; the symptom of sleepiness was a reason for not increasing the dose. One patient responded to a dose as low as 0.5 mg/d, so it is recommended that treatment start at a low dose, which may then be increased gradually. This trial is a preliminary open study with a small sample size, and further controlled studies will be necessary.

PMID 12850662  Gen Hosp Psychiatry. 2003 Jul-Aug;25(4):289-92.
著者: Dinesh Mittal, Nita A Jimerson, Emily P Neely, William D Johnson, Richard E Kennedy, Rafael A Torres, Henry A Nasrallah
雑誌名: J Clin Psychiatry. 2004 May;65(5):662-7.
Abstract/Text BACKGROUND: Effective treatment is necessary to reverse delirium and prevent potentially serious consequences.
METHOD: Patients were identified for screening by initial chart review of all consecutive admissions to the general medical or surgical wards at the Department of Veterans Affairs hospital and the University of Mississippi Medical Center in Jackson, Mississippi, between November 2000 and April 2002. Medically ill patients with delirium defined by DSM-IV criteria and a Delirium Rating Scale (DRS) score of >or= 13 were given risperidone, 0.5 mg, twice daily, with additional doses permitted on day 1 for target symptoms. Total day 1 dosage was given daily until the DRS score was RESULTS: Ten patients (mean age = 64.7 years) were enrolled. Mean daily maintenance risperidone dosage was 0.75 mg. Mean CTD scores improved from day 1 to the day maintenance dose was initiated (p <.0005) and remained improved at day 6 (7.1 +/- 2.0 and 16.9 +/- 3.0, days 1 and 6, respectively; p =.0078). Mean DRS scores improved from day 1 to the day maintenance dose was initiated (p <.0001) and remained improved at day 6 (25.2 +/- 0.9 and 11.3 +/- 1.5, days 1 and 6, respectively; p <.0001). Mean KSPS scores improved from 32.0 on day 1 to 45.5 on day 6 (p =.044). No patient developed movement disorders. One patient each discontinued because of sedation and hypotension.
CONCLUSION: Low-dose risperidone can improve cognitive and behavioral symptoms of delirium in medically ill patients.

PMID 15163252  J Clin Psychiatry. 2004 May;65(5):662-7.
著者: Yoanna K Skrobik, Nicolas Bergeron, Marc Dumont, Stewart B Gottfried
雑誌名: Intensive Care Med. 2004 Mar;30(3):444-9. doi: 10.1007/s00134-003-2117-0. Epub 2003 Dec 19.
Abstract/Text OBJECTIVE: To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.
DESIGN: Prospective randomized trial.
SETTING: Tertiary care university affiliated critical care unit.
PATIENTS: All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.
INTERVENTIONS: Patients were randomized to receive either enteral olanzapine or haloperidol.
MEASUREMENTS: Patient's delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.
MAIN RESULTS: Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.
CONCLUSIONS: Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

PMID 14685663  Intensive Care Med. 2004 Mar;30(3):444-9. doi: 10.1007/・・・
著者: William Breitbart, Annie Tremblay, Christopher Gibson
雑誌名: Psychosomatics. 2002 May-Jun;43(3):175-82. doi: 10.1176/appi.psy.43.3.175.
Abstract/Text We conducted an open, prospective trial of olanzapine for the treatment of delirium in a sample of 79 hospitalized cancer patients. Patients all met DSM-IV criteria for a diagnosis of delirium and were rated systematically with the Memorial Delirium Assessment Scale (MDAS) as a measure of delirium severity, phenomenology, and resolution, over the course of a 7-day treatment period. Sociodemographic and medical variables and measures of physical performance status and drug-related side effects were collected. Fifty-seven patients (76%) had complete resolution of their delirium on olanzapine therapy. No patients experienced extrapyramidal side effects; however, 30% experienced sedation (usually not severe enough to interrupt treatment). Several factors were found to be significantly associated with poorer response to olanzapine treatment for delirium, including age >70 years, history of dementia, central nervous system spread of cancer and hypoxia as delirium etiologies, "hypoactive" delirium, and delirium of "severe" intensity (i.e., MDAS >23). A logistic-regression model suggests that age >70 years is the most powerful predictor of poorer response to olanzapine treatment for delirium (odds ratio, 171.5). Olanzapine appears to be a clinically efficacious and safe drug for the treatment of the symptoms of delirium in the hospitalized medically ill.

PMID 12075032  Psychosomatics. 2002 May-Jun;43(3):175-82. doi: 10.1176・・・
著者: Yukiya Sasaki, Tetsuaki Matsuyama, Seishiro Inoue, Tomoko Sunami, Takeshi Inoue, Kenzo Denda, Tsukasa Koyama
雑誌名: J Clin Psychiatry. 2003 Nov;64(11):1316-21.
Abstract/Text BACKGROUND: Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impaired cognitive functioning. High-potency typical neuroleptics have traditionally been used as first-line drugs in the treatment of delirium. However, these drugs are frequently associated with undesirable adverse events including extrapyramidal symptoms (EPS). The purpose of the present open-label, flexible-dose study was to provide preliminary data on the usefulness and safety of quetiapine for patients with delirium.
METHOD: Twelve patients with DSM-IV delirium were treated with flexible doses of open-label quetiapine (mean +/- SD dosage = 44.9 +/- 31.0 mg/day). To evaluate the usefulness and safety of quetiapine, scores from the Delirium Rating Scale, Japanese version, were assessed every day (for 1 outpatient, at least twice per week), and scores from the Mini-Mental State Examination, Japanese version, and the Drug-Induced Extrapyramidal Symptom Scale were assessed at baseline and after remission of delirium. Data were gathered from April to October 2001.
RESULTS: All patients achieved remission of delirium several days after starting quetiapine (mean +/- SD duration until remission = 4.8 +/- 3.5 days). Quetiapine treatment was well tolerated, and no clinically relevant change in EPS was detected.
CONCLUSION: Quetiapine may be a useful alternative to conventional neuroleptics in the treatment of delirium due to its rapid onset and relative lack of adverse events. Further double-blind, placebo-controlled studies are warranted.

PMID 14658945  J Clin Psychiatry. 2003 Nov;64(11):1316-21.
著者: David A Straker, Peter A Shapiro, Philip R Muskin
雑誌名: Psychosomatics. 2006 Sep-Oct;47(5):385-91. doi: 10.1176/appi.psy.47.5.385.
Abstract/Text Antipsychotic drugs are the primary treatment for symptoms of delirium, but their side effects can be problematic. Treatment of delirium with aripiprazole has yet to be evaluated. The authors report on 14 patients with delirium treated with aripiprazole. Twelve patients had a >or=50% reduction in Delirium Rating Scale, Revised-98 scores, and 13 showed improvement on Clinical Global Impression scale scores. There was a low rate of adverse side effects. Aripiprazole may be an appropriate first-line agent for the treatment of delirium because of its minimal effect on QTc interval, weight, lipids, and glucose levels. Controlled comparison studies should be performed to confirm this impression.

PMID 16959926  Psychosomatics. 2006 Sep-Oct;47(5):385-91. doi: 10.1176・・・
著者: T Someya, T Endo, T Hara, G Yagi, J Suzuki
雑誌名: Psychiatry Clin Neurosci. 2001 Aug;55(4):397-401. doi: 10.1046/j.1440-1819.2001.00881.x.
Abstract/Text Delirium, which is experienced by 10-30% of inpatients, is commonly seen in daily practice. A survey was conducted of the delirium medications, and results were obtained from 28 psychiatric departments and related facilities. Haloperidol was used in 67% cases for the treatment of delirium. Ninety-seven per cent of facilities considered haloperidol as the drug of first choice, while 57% thought this drug had few side-effects and was easy to use. However, because the use of this drug is not covered by health insurance in Japan, its use is limited. We expect that this study on medication for the treatment of delirium will be a first step in increasing the approved indications for drugs used for the treatment of delirium, and to reduce off-label use.

PMID 11442892  Psychiatry Clin Neurosci. 2001 Aug;55(4):397-401. doi: ・・・
著者: Kotaro Hatta, Yasuhiro Kishi, Ken Wada
雑誌名: JAMA. 2015 Sep 8;314(10):1071-2. doi: 10.1001/jama.2015.8522.
Abstract/Text
PMID 26348758  JAMA. 2015 Sep 8;314(10):1071-2. doi: 10.1001/jama.2015・・・
著者: Kotaro Hatta, Yasuhiro Kishi, Ken Wada, Takashi Takeuchi, Shigeo Ito, Akiko Kurata, Kazunori Murakami, Manabu Sugita, Chie Usui, Hiroyuki Nakamura, DELIRIA-J Group
雑誌名: J Clin Psychiatry. 2017 Sep Oct;78(8):e970-e979. doi: 10.4088/JCP.16m11194.
Abstract/Text OBJECTIVE: No highly effective pharmacologic interventions to prevent delirium have been identified. We examined whether suvorexant, a potent and selective orexin receptor antagonist, is effective for the prevention of delirium.
METHODS: We conducted a multicenter, rater-blinded, randomized, placebo-controlled clinical trial in intensive care units and regular acute wards between April 2015 and March 2016. Eligible patients were 65 to 89 years old, newly admitted due to emergency, and able to take medicine orally and had an expected stay or life expectancy of 48 hours or more. Seventy-two patients were randomly assigned using the sealed envelope method to receive suvorexant (15 mg/d; 36 patients) or placebo (36 patients) every night for 3 days. The primary outcome measure was incidence of delirium as determined by the DSM-5. Trained psychiatrists assessed for delirium.
RESULTS: We found that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (0% [n/N = 0/36] vs 17% [6/36], respectively, P = .025). Comparison by log-rank test also showed that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (χ² = 6.46, P = .011). Analysis of variance revealed a tendency for main effect of treatment (F = 3.79, P = .053) on the sleep-wake cycle disturbance score (item 1) of the Japanese version of the Delirium Rating Scale-Revised-98 (DRS-R-98-J). There were no significant differences in adverse events.
CONCLUSIONS: Suvorexant administered nightly to elderly patients admitted for acute care may provide protection against delirium. Larger studies are needed to show the potential of suvorexant to improve the circadian core domain of delirium.
TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000015681​.

© Copyright 2017 Physicians Postgraduate Press, Inc.
PMID 28767209  J Clin Psychiatry. 2017 Sep Oct;78(8):e970-e979. doi: 1・・・

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