Cognitive Effects of Perioperative Pregabalin Secondary Exploratory Analysis of a Randomized Placebo-controlled Study

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 sub-domains of executive functioning, including inhibition, and working memory compared to placebo, whereas psychomotor speed was not changed.