title: Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty: a randomized, double-blind, placebo-controlled dose-finding study.
abstract: 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/d (group A), gabapentin 900 mg/d (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, and the secondary outcome was sedation 6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest and sedation during the first 48 hours and from days 2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, headache, visual disturbances, and adverse reactions. Pain upon ambulation (visual analog scale, mean [95% confidence interval]) 24 hours after surgery in group A vs B vs C was as follows: 41 [37-46] vs 41 [36-45] vs 42 [37-47], P = 0.93. Sedation (numeric rating scale, median [range]) 6 hours after surgery was as follows: 3.2 [0-10] vs 2.6 [0-9] vs 2.3 [0-9], the mean difference A vs 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 48 hours and from days 2-6. Sleep quality was better during the first 2 nights in group A and B vs C. Dizziness was more pronounced from days 2-6 in A vs C. More severe adverse reactions were observed in group A vs B and C. In conclusion, gabapentin may have a limited if any role in acute postoperative pain management of opioid-naive patients undergoing total knee arthroplasty and should not be recommended as a standard of care.
authors.affiliation: Department of Anesthesiology, Copenhagen University Hospital, Hvidovre, Denmark The Lundbeck Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen, Denmark Department of Orthopedic Surgery, Copenhagen University Hospital, Hvidovre, Denmark Department of Orthopedic Surgery, Aalborg University Hospital, Farsø, Denmark Department of Orthopedic Surgery, South of Denmark University Hospital, Grindsted, Denmark Section of Surgical Pathophysiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Troels Haxholdt
authors.initials: TH
authors.lastname: Lunn
authors.forename: Henrik
authors.initials: H
authors.lastname: Husted
authors.forename: Mogens Berg
authors.initials: MB
authors.lastname: Laursen
authors.forename: Lars Tambour
authors.initials: LT
authors.lastname: Hansen
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000588:Amines / Q000008:administration & dosage* / Q000009:adverse effects; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000627:therapeutic use; D019645:Arthroplasty, Replacement, Knee; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000077206:Gabapentin; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy / Q000517:prevention & control*; D012890:Sleep; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D006993:Hypnotics and Sedatives; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine