【原】【罂粟摘要】米诺环素对拟行全膝关节置换术的老年患者术后认知功能障碍的预防：一项随机、双盲、安慰剂对照临床试验

米诺环素对拟行全膝关节置换术的老年患者术后认知功能障碍的预防：一项随机、双盲、安慰剂对照临床试验

贵州医科大学             麻醉与心脏电生理课题组

翻译：宋雨婷           编辑：宋雨婷         审校：曹莹

背景

在临床实践中，暂无有效的药物来预防术后认知功能障碍。已知抗生素米诺环素可抑制术后神经炎症，本试验旨在研究米诺环素是否能够预防非心脏手术患者术后认知功能障碍。

方法

这项研究纳入60岁以上在全麻下拟行全膝关节置换术的患者。将其随机分为米诺环素组（术前一天到术后第七天每天两次口服100mg米诺环素）和安慰剂组（术前一天到术后第七天每天两次口服安慰剂）。在术前以及术后1周和术后3个月评估患者认知功能，使用四种认知功能测试，包括视觉语言学习测试，连线测验，斯特鲁普色词测验以及字母数字编码任务。此外，30名健康志愿者接受了与受试对象相同的测试，以检测重复测试的学习效力。在考虑到学习效力的前提下，根据一系列神经认知测试的结果判断术后认知功能障碍的发生率。次要结局指标是米诺环素对术后谵妄和术后疼痛的影响。

结果

共有100名患者随机分配到米诺环素组，102名患者随机分配到安慰剂组。患者平均年龄为75岁。评估显示，米诺环素组和安慰剂组在术后1周（8/90人[8.9%]比4/95人[4.2%]；比值比 2.22 [95%CI，0.64-7.65]；P = 0.240）和术后3个月15.3/90 [17.0%]比15.3/95 [16.1%]；比值比 1.07 [95% CI，0.49-2.32]；P = 0.889）的术后认知功能障碍发生率差异无统计学意义。术后3个月的缺失数据通过多重归因法进行校正。两组在术后谵妄和术后疼痛方面无差异。

结论

米诺环素可能对术后认知功能障碍无预防作用。

原始文献来源

Tomonori Takazawa, Tatsuo Horiuchi, Masaki Orihara, et al. Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial. Anesthesiology 2023; 138:172–183.

英文原文

Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial

Background: There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery.

Methods: This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter–Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain.

Results: A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain.

Conclusions: Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction.