title: Pregabalin Has Analgesic, Ventilatory, and Cognitive Effects in Combination with Remifentanil.
abstract: 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.
authors.affiliation: From the Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, and Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway (M.M.); Oslo Centre for Biostatistics and Epidemiology, Research Support Services, Department of Biostatistics, Oslo University Hospital, Oslo, Norway (L.M.D.); and Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (A.S.).
authors.forename: Marianne
authors.initials: M
authors.lastname: Myhre
authors.forename: Lien My
authors.initials: LM
authors.lastname: Diep
authors.forename: Audun
authors.initials: A
authors.lastname: Stubhaug
mesh_terms: D000328:Adult; D000700:Analgesics / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010880:Piperidines / Q000494:pharmacology*; D000069583:Pregabalin / Q000494:pharmacology*; D000077208:Remifentanil; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives; D010880:Piperidines; D000069583:Pregabalin; D000077208:Remifentanil