Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty A randomized, double-blind, placebo-controlled, dose-finding study

Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs. harm have not been clarified. In this randomized, double-blind, placebo-controlled, dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized (1:1:1) to either gabapentin 1300 mg/day (group A), gabapentin 900mg/day (group B) or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery, the secondary outcome sedation6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest, and sedation during the first 48hours and from day2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, head-ache, visual disturbances, and adverse reactions. Pain upon ambulation [VAS, mean (95% CI)] 24hours after surgery in group A vs. B vs. C was: 41(37-46) vs.41(36-45) vs.42(37-47), p=0.93. Sedation [NRS, median (range)] 6hours after surgery was: 3.2(0-10) vs.2.6 (0-9) vs.2.3 (0-9), the mean difference Avs.C being 0.9(0.2-1.7),p=0.046. No between-group differences were observed in overall pain or morphine use the first 48hours and from day2-6. Sleep quality was better during the first 2 nights in group A and Bvs.C. Dizziness was more pronounced from day2-6 in Avs. C. More severe adverse reactions were observed in group Avs.B and C. In conclusion, gabapentin may have limited if any role in acute postoperative pain management of opioid-naive patients undergoing total knee arthroplasty and should not be recommended as standard of care.