术后给予毒扁豆碱预防肝手术患者术后谵妄和长期认知功能障碍：一项双盲随机对照试验。
Physostigmine for prevention of postoperative delirium and long-term cognitive dysfunction in liver surgery: A double-blinded randomised controlled trial.
机构信息
From the Department of Anaesthesiology and Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, and Berlin Institute of Health (CDS, CK, MM, W-RB, AS, AF, OM, VK, MF, WA, FB), Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, and Berlin Institute of Health (JW, KDW, SKP), Berlin Institute of Health (BIH), Anna-Louisa-Karsch 2, Berlin, Germany (JW, SKP), Addenbrooke's Hospital, Division of Anaesthesia, University of Cambridge, Cambridge, UK (KK, DKM), Department of Surgery (JP), Institute of Immunology, Charité - Universitätsmedizin Berlin, and Berlin Institute of Health (LA), Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany (LA), Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, and the Veteran's Affairs Tennessee Valley Geriatric Research Education Clinical Center (GRECC), USA (EWE) and SOSTANA GmbH Berlin, Germany (KDW).
出版信息
Eur J Anaesthesiol. 2021 Sep 1;38(9):943-956. doi: 10.1097/EJA.0000000000001456.
BACKGROUND
Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction.
OBJECTIVE
The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection.
DESIGN
This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery.
SETTING
This single-centre study was conducted at an academic medical centre.
PARTICIPANTS
In total, 261 participants aged at least 18 years scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD).
INTERVENTION
Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02 mg kg-1 body weight followed by 0.01 mg kg-1 body weight per hour (n = 130), or placebo (n = 131), for 24 h after induction of anaesthesia.
MAIN OUTCOMES AND MEASURES
Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365.
RESULTS
In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; P = 0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3 months [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), P = 0.002], and 6 months [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), P = 0.012] after surgery.
CONCLUSION
Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24 h.
TRIAL REGISTRATION
DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11 618/08 (15 January 2009).
背景
据报道，胆碱能刺激已被用于治疗谵妄并减少认知功能障碍。
目的
本研究旨在评估毒扁豆碱是否能降低行肝切除术患者术后谵妄（POD）和术后认知功能障碍（POCD）的发生率。
设计
这是一项双盲、随机、安慰剂对照试验。2009 年 8 月 11 日至 2016 年 3 月 3 日期间，在德国柏林夏里特大学医学中心招募了患者。随访在术后 1 周（T1）、90 天（T2）和 365 天（T3）进行。
地点
这项单中心研究在一家学术医疗中心进行。
参与者
共纳入 261 名年龄至少 18 岁、计划接受择期肝手术的患者进行随机分组。该方案还纳入了 45 名非手术匹配对照者，以提供 POCD 和神经认知缺陷（NCD）的正常数据。
干预
参与者被分配接受静脉内毒扁豆碱，首剂量为 0.02mg/kg 体重，随后每小时给予 0.01mg/kg 体重，持续 24 小时，麻醉诱导后使用（n=130），或安慰剂（n=131）。
主要结局和测量
主要结局为 POD，使用精神障碍诊断和统计手册（DSM-4-TR）每天两次评估，直至术后第 7 天；POCD 通过 CANTAB 神经心理测试套件以及术前 1 天和术后第 7、90 和 365 天的两项纸笔测试进行评估。
结果
共随机分配了 261 名患者，130 名患者接受毒扁豆碱治疗，131 名患者接受安慰剂治疗。毒扁豆碱组和安慰剂组 POD 的发生率无显著差异（20%与 15%；P=0.334）。在任何时间，毒扁豆碱组和安慰剂组的术前认知障碍和 POCD 发生率均无显著差异。与安慰剂组相比，毒扁豆碱组术后 3 个月（2%[95%置信区间（CI），0 至 4]与 11%[95%CI，6 至 16]，P=0.002）和 6 个月（7%[95%CI，3 至 12]与 16%[95%CI，10 至 23]，P=0.012）的死亡率较低。
结论
麻醉诱导后使用毒扁豆碱长达 24 小时，对 POD 和 POCD 无影响。
试验注册
DOI 10.1186/ISRCTN18978802，EudraCT 2008-007237-47，伦理批准 ZS EK 11 618/08（2009 年 1 月 15 日）。
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