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せん妄に対する薬物療法アルゴリズム

興奮や幻覚などの異常体験が著明な場合には、薬剤による鎮静が必要である。
出典
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1: 日本総合病院精神医学会せん妄指針改定班(総括:八田耕太郎)編集:増補改訂せん妄の臨床指針 せん妄の治療指針第2版. p100. 星和書店, 2015

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。
出典
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1: 一瀬邦弘,田中邦明,長田憲一ら. 老年精神医学雑誌,3(11):1201-1200,1992

せん妄発症群では、手術前のNK細胞値が低く、血漿MHPG値が高い。

手術時にせん妄を発症する人と発症しない人がいるが、せん妄発症には患者側の脆弱性が関連している可能性がある。不安の指標と考えられているノルアドレナリンの代謝産物である3-methoxy-4- hydroxyphenyl (ethylene) glycol (MHPG)が手術前に高く、免疫活性の指標であるナチュラルキラー細胞活性値(NK)が低い人はせん妄が発症する可能性がある。
出典
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1: Association of plasma free-3-methoxy-4-hydroxyphenyl (ethylene)glycol, natural killer cell activity and delirium in postoperative patients.
著者: J Nakamura, R Yoshimura, T Okuno, N Ueda, M Hachida, K Yasumoto, H Egami, H Maeda, M Nishi, S Aoyagi
雑誌名: Int Clin Psychopharmacol. 2001 Nov;16(6):339-43.
Abstract/Text: We measured and compared levels of plasma free 3-methoxy-4-hydroxyphenyl (ethylene)glycol (pMHPG), a major metabolite of noradrenaline, and natural killer (NK) cell activity in 26 patients prior to their undergoing an operation for cardiovascular diseases; 11 of whom expressed delirium and 15 who did not. In conclusion, we found that pMHPG levels before an operation were higher in patients with postoperative delirium than in the patients without, while NK cell activity showed no difference between the two groups. It is possible that hyperactivity of noradrenargic neurons is connected with the development of postoperative delirium. Furthermore, we considered that measurement of pMHPG level before operation might be a useful tool to predict the occurrence of postoperative delirium.
Int Clin Psychopharmacol. 2001 Nov;16(6):339-43.

DRS-R-98スコアシート

出典
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1: Paula T, Trzepacz, 岸 泰宏, 保坂 隆, 古川栄省, 中村優里:精神医学, 43(12): 1365-1371, 2001

せん妄に対する非薬物療法に関するネットワークメタ解析結果

a. せん妄発症率 b. せん妄の持続期間 c. ICU収容期間 d. 院内での死亡
PEI:身体的環境調整、SR:鎮静減弱、FP:家族参画、EP:運動プログラム、
CHI:脳循環改善、MLT:多面的な介入、UC:usual care 通常ケア
 
参考文献:
Wu YC, Tseng PT,Tu YK, Chung-Yao Hsu CY, Liang CS, Yeh TC, Chen TT, Chu CS, Matsuoka YJ, Stubbs B, Carvalho AF, Wada S, Lin PY, Chen YW. Su KP:Association of delirium response and safety of pharmacological intervention for the manegement and prevention of delirium. A netowork meta-anlysis. JAMA Psychiatry, 2019 May 1:76(5): 526-535. PMID:30810723
出典
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1: Non-pharmacological interventions to reduce the incidence and duration of delirium in critically ill patients: A systematic review and network meta-analysis.
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.
J Crit Care. 2020 Aug 31;60:241-248. doi: 10.1016/j.jcrc.2020.08.019. ...

各種薬剤に対するプラセボあるいは対照と比較したネットワークメタ解析のネットワーク構造

参考文献:
中村 純:せん妄の病態と治療. 仁明会精神医学研究 2019; 17(1):16-22.
出典
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1: Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis.
著者: Yi-Cheng Wu, Ping-Tao Tseng, Yu-Kang Tu, Chung-Yao Hsu, Chih-Sung Liang, Ta-Chuan Yeh, Tien-Yu Chen, Che-Sheng Chu, Yutaka J Matsuoka, Brendon Stubbs, Andre F Carvalho, Saho Wada, Pao-Yen Lin, Yen-Wen Chen, Kuan-Pin Su
雑誌名: JAMA Psychiatry. 2019 May 1;76(5):526-535. doi: 10.1001/jamapsychiatry.2018.4365.
Abstract/Text: Importance: Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear.
Objective: To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention.
Data Sources: PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018.
Study Selection: Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention.
Data Extraction and Synthesis: To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model.
Main Outcomes and Measures: The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium.
Results: A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control.
Conclusions and Relevance: This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.
JAMA Psychiatry. 2019 May 1;76(5):526-535. doi: 10.1001/jamapsychiatry...

せん妄の薬物治療に使用される向精神薬の特徴

※2014年以降、倫理規定の改訂により、抗精神病薬の適用外使用を目的とした臨床試験が困難となり、症例報告レベルでもほとんど報告がない。
出典
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1: 宇都宮健輔・中村 純: せん妄の最新薬物治療ガイドライン 臨床精神薬理 2011;14(6):969 – 976.

せん妄発症の要因と治療的な介入

せん妄発症の要因を分析して、準備因子だけの場合、誘発因子がある場合、直接因子を有する場合に分けて、薬剤を選択する。
 
※2014年以降、倫理規定の改訂により、抗精神病薬の適用外使用を目的とした臨床試験が困難となり、症例報告レベルでもほとんど報告がない。
出典
img
1: 一瀬邦弘ら:老年精神医学雑誌 1992;3(11):1201-1209改変

せん妄に対する薬物療法アルゴリズム

興奮や幻覚などの異常体験が著明な場合には、薬剤による鎮静が必要である。
出典
img
1: 日本総合病院精神医学会せん妄指針改定班(総括:八田耕太郎)編集:増補改訂せん妄の臨床指針 せん妄の治療指針第2版. p100. 星和書店, 2015

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。
出典
img
1: 一瀬邦弘,田中邦明,長田憲一ら. 老年精神医学雑誌,3(11):1201-1200,1992