Plasma orexin-A levels in patients with delirium

Plasma orexin-A levels in patients with delirium
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谵妄患者血浆食欲素 A 水平

DOI:
10.1111/psyg.12444
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发表时间:
2019
期刊:
影响因子:
2
通讯作者:
Masafumi Kuzuya
Masafumi Kuzuya
中科院分区:
医学4区
文献类型:
--
作者:
Hirotaka Nakashima;Hiroyuki Umigaki;Madoka Yanagawa;Hitoshi Komiya;Kazuhisa Watanabe;Masafumi Kuzuya

文献摘要

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谵妄的病理生理机制仍然知之甚少。最近,睡眠药物suvorexant,一种食欲素受体拮抗剂,显示出对谵妄的预防作用。1然而,尚不清楚苏沃雷生对食欲素的调节是否直接影响谵妄的发生。虽然测量脑脊液(CSF)中的食欲素水平是理想的,但由于安全风险,通常难以对谵妄患者进行腰椎穿刺;此外,这样做存在伦理问题。一些研究已经证明了CSF和血浆样品中食欲素-A水平之间的相关性。2这项前瞻性队列研究旨在评估血浆食欲素A水平与谵妄之间的关系。我们入组了2017年12月1日至2018年1月31日期间入住名古屋大学医院老年病房的70例年龄≥ 65岁的患者。排除标准如下:(i)目前正在服用苏沃雷生;(ii)入院后10天内有固定的出院时间表;或(iii)重度意识障碍(格拉斯哥昏迷量表评分≤ 8)。从参与者或其家庭成员处获得书面知情同意书。本研究遵循赫尔辛基宣言的原则,并获得了名古屋大学医学研究生院伦理委员会的批准。每例患者在第2 - 4天进行血液采样和谵妄评价。在0700 - 0800小时之间采集空腹血液,置于含有乙二胺四乙酸二钠和抑肽酶的3 mL试管中。采血后,将试管储存在4 ℃冰箱中。在2小时内,将血液在室温下以3000 rpm离心10 min。将获得的血浆储存在-80 ℃下直至分析。血浆食欲素-A水平由SRL Inc.(东京,日本)与市售放射免疫测定试剂盒(半岛实验室国际公司,San卡洛斯,CA,USA)。在采血后1小时内,两名老年病学家根据《诊断和统计手册》的标准独立诊断为谵妄。
The pathophysiology of delirium remains poorly understood. Recently, the sleep medication suvorexant, an orexin receptor antagonist, showed a preventive effect on delirium. 1 However, it remains unclear whether regulation of orexin by suvorexant directly affects the development of delirium. Although measuring orexin levels in cerebrospinal fluid (CSF) is ideal, it is often difficult to perform a lumbar puncture in patients with delirium because of safety risks; additionally, doing so presents ethical problems. A few studies have demonstrated a correlation between orexin-A levels in CSF and in plasma samples. 2 This prospective cohort study aimed to evaluate the association between plasma orexin-A levels and delirium. We enrolled 70 patients aged≥ 65 years who were admitted to the geriatric ward of Nagoya University Hospital between 1 December 2017 and 31 January 2018. Exclusion criteria were as follows:(i) currently taking suvorexant;(ii) having a fixed schedule for discharge within 10 days of admission; or (iii) severe disturbance of consciousness (Glasgow Coma Scale score≤ 8). Written informed consent was obtained from participants or their family members. This study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Nagoya University Graduate School of Medicine. Each patient underwent blood sampling and evaluation for delirium on days 2-4. Fasting blood was collected between 0700 and 0800 hours in a 3-mL tube containing ethylene diamine tetra-acetic acid disodium and aprotinin. After blood sampling, the tubes were stored in a refrigerator at 4 C. Within 2 h, the blood was centrifuged for 10 min at 3000 rpm at room temperature. The obtained plasma was stored at− 80 C until analysis. Plasma orexin-A levels were measured by SRL Inc.(Tokyo, Japan) with a commercially available radioimmunoassay kit (Peninsula Laboratories International, Inc., San Carlos, CA, USA). Within 1 h after blood sampling, two geriatricians independently diagnosed delirium based on the criteria of the Diagnostic and Statistical Manual of