title: Postoperative pain treatment after total knee arthroplasty: A systematic review.
abstract: BACKGROUND
  The aim of this systematic review was to document efficacy, safety and quality of evidence of analgesic interventions after total knee arthroplasty (TKA).
  
  
  METHODS
  This PRISMA-compliant and PROSPERO-registered review includes all-language randomized controlled trials of medication-based analgesic interventions after TKA. Bias was evaluated according to Cochrane methodology. Outcomes were opioid consumption (primary), pain scores at rest and during mobilization, adverse events, and length of stay. Interventions investigated in three or more trials were meta-analysed. Outcomes were evaluated using forest plots, Grading of Recommendations Assessment, Development and Evaluation (GRADE), L'Abbe Plots and trial sequential analysis.
  
  
  RESULTS
  The included 113 trials, investigating 37 different analgesic interventions, were characterized by unclear/high risk of bias, low assay sensitivity and considerable differences in pain assessment tools, basic analgesic regimens, and reporting of adverse events. In meta-analyses single and continuous femoral nerve block (FNB), intrathecal morphine, local infiltration analgesia, intraarticular injection of local anaesthetics, non-steroidal anti-inflammatory drugs, and gabapentinoids demonstrated significant analgesic effects. The 24-hour morphine-sparing effects ranged from 4.2 mg (CI: 1.3, 7.2; intraarticular local anaesthetics), to 16.6 mg (CI: 11.2, 22; single FNB). Pain relieving effects at rest at 6 hours ranged from 4 mm (CI: -10, 2; gabapentinoids), to 19 mm (CI: 8, 31; single FNB), and at 24 hours from 3 mm (CI: -2, 8; gabapentinoids), to 16 mm (CI: 8, 23; continuous FNB). GRADE-rated quality of evidence was generally low.
  
  
  CONCLUSIONS
  A low quality of evidence, small sample sizes and heterogeneity of trial designs prohibit designation of an optimal procedure-specific analgesic regimen after TKA.
authors.affiliation: Department of Anaesthesia, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.|Department of Anaesthesia, Zealand University Hospital, Koege, Denmark.
authors.forename: Anders Peder Højer
authors.identifier: http://orcid.org/0000-0002-0338-3751
authors.initials: AP
authors.lastname: Karlsen
authors.affiliation: Department of Anaesthesia, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Mik
authors.initials: M
authors.lastname: Wetterslev
authors.affiliation: Department of Anaesthesia, Slagelse Hospital, Slagelse, Denmark.
authors.forename: Signe Elisa
authors.initials: SE
authors.lastname: Hansen
authors.affiliation: Department of Anaesthesia, 4231, Centre of head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten Sejer
authors.initials: MS
authors.lastname: Hansen
authors.affiliation: Department of Anaesthesia, Zealand University Hospital, Koege, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mathiesen
authors.affiliation: Department of Anaesthesia, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
authors.forename: Jørgen B
authors.initials: JB
authors.lastname: Dahl
mesh_terms: D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D059408:Pain Management; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000628:therapy*; D016896:Treatment Outcome