Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial
Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial
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DOI：
10.1097/aln.0000000000004439
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发表时间：
2023-02-01
期刊：
影响因子：
8.8
通讯作者：
Saito，Shigeru
中科院分区：
文献类型：
--
作者：
Takazawa，Tomonori;Horiuchi，Tatsuo;Saito，Shigeru
背景在日常实践中，没有有效的药物干预来预防术后认知功能障碍。由于抗生素二甲胺四环素是已知的，以抑制术后神经炎症，本研究假设和调查是否二甲胺四环素可能有预防作用术后认知功能障碍after noncardiac surgery.MethodsThis study includes patients against more than 60 yr undergoing total knee arthroplasty under general anesthesia.他们被随机分配到米诺环素和安慰剂组，口服米诺环素或安慰剂100毫克，每天两次，从手术前一天到手术后第七天。在术前、术后1周和3个月，使用一组四项认知功能测试评估认知功能，包括视觉语言学习测试、连线测试、Stroop颜色和单词测试以及字母-数字编码任务。此外，30名健康志愿者接受了与患者相同的测试，以检查重复测试的学习效果。术后认知功能障碍的发生根据神经认知成套测验的结果进行判断，并考虑学习效果。次要终点是米诺环素对术后谵妄和术后疼痛的影响。ResultsA共100例患者被随机分配到米诺环素组，102例被随机分配到安慰剂组。患者平均年龄75岁。评价显示，在1周时，二甲胺四环素组和安慰剂组之间术后认知功能障碍的发生率无显著差异（8/90 [8.9%] vs. 4/95 [4.2%];比值比，2.22 [95% CI，0.64 - 7.65]; P= 0.240）和3个月（15.3/90 [17.0%] vs. 15.3/95 [16.1%];比值比，1.07 [95%CI，0.49 - 2.32]; P= 0.889）。术后3个月的缺失数据通过多重插补方法进行校正。两组患者术后谵妄和术后疼痛无差异。
BackgroundThere 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.MethodsThis 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.ResultsA 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