title: Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial.
abstract: BACKGROUND
  Pregabalin may reduce postoperative pain and opioid use. Higher doses may be more effective, but may cause sedation and confusion. This prospective, randomized, blinded, placebo-controlled study tested the hypothesis that pregabalin reduces pain at 2 weeks after total knee arthroplasty, but increases drowsiness and confusion.
  
  
  METHODS
  Patients (30 per group) received capsules containing pregabalin (0, 50, 100, or 150 mg); two capsules before surgery, one capsule twice a day until postoperative day (POD) 14, one on POD15, and one on POD16. Multimodal analgesia included femoral nerve block, epidural analgesia, oxycodone-paracetamol, and meloxicam. The primary outcome was pain with flexion (POD14).
  
  
  RESULTS
  Pregabalin did not reduce pain at rest, with ambulation, or with flexion at 2 weeks (P=0.69, 0.23, and 0.90, respectively). Pregabalin increased POD1 drowsiness (34.5, 37.9, 55.2, and 58.6% in the 0, 50, 100, and 150 mg arms, respectively; P=0.030), but did not increase confusion (0, 3.5, 0, and 3.5%, respectively; P=0.75). Pregabalin had no effect on acute or chronic pain, opioid consumption, or analgesic side-effects. Pregabalin reduced POD14 patient satisfaction [1-10 scale, median (first quartile, third quartile): 9 (8, 10), 8 (7, 10), 8 (5, 9), and 8 (6, 9.3), respectively; P=0.023). Protocol compliance was 63% by POD14 (50.0, 70.0, 76.7, and 56.7% compliance, respectively), with no effect of dose on compliance. Per-protocol analysis of compliant patients showed no effect of pregabalin on pain scores.
  
  
  CONCLUSIONS
  Pregabalin had no beneficial effects, but increased sedation and decreased patient satisfaction. This study does not support routine perioperative pregabalin for total knee arthroplasty patients.
  
  
  BACKGROUND
  ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/study/NCT01333956.
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA yadeauj@hss.edu.
authors.forename: J T
authors.initials: JT
authors.lastname: YaDeau
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Deparment of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Mayman
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Goytizolo
authors.affiliation: Deparment of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Alexiades
authors.affiliation: Deparment of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Padgett
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Kahn
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Jules-Elysee
authors.affiliation: Deparment of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Ranawat
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Bhagat
authors.affiliation: Healthcare Research Institute, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: K G
authors.initials: KG
authors.lastname: Fields
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Goon
authors.affiliation: Department of Anesthesiology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: J
authors.initials: J
authors.lastname: Curren
authors.affiliation: Deparment of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Westrich
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use*; D019645:Arthroplasty, Replacement, Knee; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D000069583:Pregabalin; D011446:Prospective Studies; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
keywords: analgesia; anticonvulsants; arthroplasty; knee; pain management; perioperative care; replacement