围术期普瑞巴林使用对认知功能的影响：随机安慰剂对照研究的二次探索性分析
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Cognitive Effects of Perioperative Pregabalin ： Secondary Exploratory Analysis of a Randomized Placebo-controlled Study
背景与目的
普瑞巴林在术后早期具镇痛作用且可减少阿片类药物的应用，但其在围术期对认知功能的影响尚未有人研究。已有研究证实普瑞巴林的镇痛作用及其对阿片类药物节余作用和镇痛作用的影响。本文旨在探讨普瑞巴林对认知功能的影响。
方 法
本试验为随机、安慰剂对照研究80名择期进行肾切除术的患者参与了这项。除了由阿片类药物、类固醇、局部麻醉剂和对乙酰氨基酚组成的镇痛方案外，在手术当天和术后第一天使用普瑞巴林(150毫克，每日两次，n = 40)或安慰剂(n = 40)。具体的认知测试包括基线水平上测试患者的抑制能力、持续注意力、心理运动速度、视觉记忆和策略，在手术后24小时和3 - 5天进行，使用剑桥神经心理测试自动化电池(Cambridge Neuropsychological Test Automated Battery)。
结 果
在术后24小时空间工作记忆测试的错误测试中，与安慰剂组相比，普瑞巴林组的错误数增加;中位数(25、75个百分点)分别为1(0,6)和0 (0,1);比率[95% CI]， 3.20 [1.55 ~ 6.62];P = 0.002)。此外，与安慰剂相比，普瑞巴林在停止信号任务和停止-行动测试中的错误数量显著增加;中位数(25、75个百分点)分别为3(1,6)和1 (0,2);比率，2.14[1.13至4.07];P = 0.020)。在配对相关学习、反应时间、快速视觉处理或空间工作记忆策略测试中，两组间无显著差异。
结 论
与安慰剂相比，围手术期使用普瑞巴林对抑制功能领域和包括工作记忆在内的执行功能亚区有显著负性影响，而对精神运动速度没有影响。
原始文献摘要
Marianne Myhre, Henrik Børsting Jacobsen,Stein Andersson;Cognitive Effects of Perioperative Pregabalin
Secondary Exploratory Analysis of a Randomized Placebo-controlled Study; Anesthesiology 2019; 130:63–71
Background: Pregabalin has shown opioid sparing and analgesic effects in the early postoperative period; however, perioperative effects on cognition have not been studied. A randomized, parallel group, placebo-controlled investigation in 80 donor nephrectomy patients was previously performed that evaluated the analgesic, opioid-sparing, and antihyperalgesic effects of pregabalin. This article describes a secondary exploratory analysis that tested the hypothesis that pregabalin would impair cognitive function compared to placebo.
Methods: Eighty patients scheduled for donor nephrectomy participated in this randomized, placebo-controlled study. Pregabalin (150 mg twice daily, n = 40) or placebo (n = 40) was administered on the day of surgery and the first postoperative day, in addition to a pain regimen consisting of opioids, steroids, local anesthetics, and acetaminophen. Specific cognitive tests measuring inhibition, sustained attention, psychomotor speed, visual memory, and strategy were performed at baseline, 24 h, and 3 to 5 days after surgery, using tests from the Cambridge Neuropsychological Test Automated Battery.
Results: In the spatial working memory within errors test, the number of errors increased with pregabalin compared to placebo 24 h after surgery; median (25th, 75th percentile) values were 1 (0, 6) versus 0 (0, 1; rate ratio [95% CI], 3.20 [1.55 to 6.62]; P = 0.002). Furthermore, pregabalin significantly increased the number of errors in the stop-signal task stop-go test compared with placebo; median (25th, 75th percentile) values were 3 (1, 6) versus 1 (0, 2; rate ratio, 2.14 [1.13 to 4.07]; P = 0.020). There were no significant differences between groups in the paired associated learning, reaction time, rapid visual processing, or spatial working memory strategy tests.
Conclusions: Perioperative pregabalin significantly negatively affected subdomains of executive functioning, including inhibition, and working memory compared to placebo, whereas psychomotor speed was not changed.
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