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

Pregabalin Has Analgesic, Ventilatory, and Cognitive Effects in Combination with Remifentanil.

BACKGROUND: Pregabalin is widely used perioperatively. The authors explored the effects of pregabalin, remifentanil, and their combination on experimental pain, ventilatory, and cognitive function. METHODS: In a randomized, double-blinded crossover study, 12 volunteers received (1) pregabalin + placebo, (2) placebo + remifentanil, (3) pregabalin + remifentanil, and (4) placebo + placebo. Pregabalin 150 mg/placebo was administered twice orally. After baseline, remifentanil/placebo was given as effect-site target-controlled infusion (TCI): 0.6, 1.2, and 2.4 ng/ml. Pain during cold pressor test was scored on visual analog scale (0 to 100 mm). Ventilation was measured by spirometry and cognition tested with Color-Word Interference and Rapid Information Processing tests. RESULTS: Pain intensity after placebo was (mean) 72 mm (95% CI, 62 to 83). Pregabalin reduced pain score by -10 mm (-14 to -7, P < 0.001). Remifentanil had dose-dependent analgesic effect, reducing pain score by -47 mm (-54 to -39, P < 0.001) on highest TCI level, whereas pregabalin + remifentanil exerted additive effect, reducing pain score by -57 mm (-64 to -50, P < 0.001). Respiratory depression was potentiated by adding pregabalin to remifentanil; end-tidal carbon dioxide was 39.3 mmHg (37.2 to 41.3) with placebo, increased 1.8 mmHg (-0.9 to 4.6, P = 0.4) with pregabalin, 10.1 mmHg (4.9 to 15.4, P < 0.001) with remifentanil, and 16.4 mmHg (11.3 to 21.5, P < 0.001) with pregabalin + remifentanil on highest TCI level. The combination pregabalin + remifentanil, but not either drug alone, adversely affected all cognitive tests. CONCLUSIONS: The combination of pregabalin and remifentanil had additive analgesic effects, pregabalin potentiated remifentanil ventilatory depression, and the combination adversely affected cognition. These results question the clinical benefit of the combination compared with higher doses of opioids.