A Systematic Review of the Efficacy and Safety of Ketamine in Total Joint Arthroplasty

Published:October 31, 2022DOI:



      Ketamine is administered intraoperatively to treat pain associated with primary total hip (THA) and knee arthroplasty (TKA). The purpose of this study was to evaluate the efficacy and safety of ketamine in primary THA and TKA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons (AAHKS), American Academy of Orthopaedic Surgeons (AAOS), Hip Society, Knee Society, and the American Society of Regional Anesthesia and Pain Management (ASRA).


      The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published prior to 2020 on ketamine in THA and TKA. All included studies underwent qualitative assessment and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of ketamine. After a critical appraisal of 136 publications, 7 high-quality studies were included for analyses.


      High-quality evidence demonstrates that intraoperative ketamine decreases postoperative opioid consumption. Four of 7 studies found that ketamine reduces postoperative pain. Intraoperative ketamine is not associated with an increase in adverse events and may reduce postoperative nausea and vomiting (relative risk [RR] 0.68; 95% CI 0.50-0.92).


      High-quality evidence supports the use of ketamine intraoperatively in THA and TKA to reduce postoperative opioid consumption. Most studies found ketamine reduces postoperative pain, nausea, and vomiting. Moderate quality evidence supports the safety of ketamine, but it should be used cautiously in patients at risk for postoperative delirium, such as the elderly.


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        • Halawi M.J.
        • Grant S.A.
        • Bolognesi M.P.
        Multimodal analgesia for total joint arthroplasty.
        Orthopedics. 2015; 38: e616-e625
        • Tali M.
        • Maaroos J.
        Lower limbs function and pain relationships after unilateral total knee arthroplasty.
        Int J Rehabil Res. 2010; 33: 264-267
        • Parvizi J.
        • Miller A.G.
        • Gandhi K.
        Multimodal pain management after total joint arthroplasty.
        J Bone Joint Surg Am. 2011; 93: 1075-1084
        • Moucha C.S.
        • Weiser M.C.
        • Levin E.J.
        Current strategies in anesthesia and analgesia for total knee arthroplasty.
        J Am Acad Orthop Surg. 2016; 24: 60-73
        • Elia N.
        • Tramèr M.R.
        Ketamine and postoperative pain – a quantitative systematic review of randomised trials.
        Pain. 2005; 113: 61-70
        • Bell R.F.
        • Dahl J.B.
        • Moore R.A.
        • Kalso E.
        Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review).
        Acta Anaesthesiol Scand. 2005; 49: 1405-1428
        • Wang P.
        • Yang Z.
        • Shan S.
        • Cao Z.
        • Wang Z.
        Analgesic effect of perioperative ketamine for total hip arthroplasties and total knee arthroplasties: a PRISMA-compliant meta-analysis.
        Medicine. 2020; 99: e22809
        • Riddell J.M.
        • Trummel J.M.
        • Onakpoya I.J.
        Low-dose ketamine in painful orthopaedic surgery: a systematic review and meta-analysis.
        Br J Anaesth. 2019; 123: 325-334
        • Xu B.
        • Wang Y.
        • Zeng C.
        • Wei J.
        • Li J.
        • Wu Z.
        • et al.
        Analgesic efficacy and safety of ketamine after total knee or hip arthroplasty: a meta-analysis of randomised placebo-controlled studies.
        BMJ Open. 2019; 9: e028337
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • Group P.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        BMJ. 2009; 339: b2535
      1. Surgeons AA of O. AAOS Clinical Practice Guideline and Systematic Review Methodology n.d.:14.

        • Adam F.
        • Chauvin M.
        • Manoir B.D.
        • Langlois M.
        • Sessler D.I.
        • Fletcher D.
        Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty.
        Anesth Analg. 2005; 100: 475-480
        • Aveline C.
        • Roux A.L.
        • Hetet H.L.
        • Gautier J.F.
        • Vautier P.
        • Cognet F.
        • et al.
        Pain and recovery after total knee arthroplasty.
        Clin J Pain. 2014; 30: 749-754
        • Aveline C.
        • Gautier J.F.
        • Vautier P.
        • Cognet F.
        • Hetet H.L.
        • Attali J.Y.
        • et al.
        Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam.
        Eur J Pain. 2009; 13: 613-619
        • Cengiz P.
        • Gokcinar D.
        • Karabeyoglu I.
        • Topcu H.
        • Cicek G.S.
        • Gogus N.
        Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.
        J Coll Physicians Surg Pak. 2014; 24: 299-303
        • Martinez V.
        • Cymerman A.
        • Ammar S.B.
        • Fiaud J.F.
        • Rapon C.
        • Poindessous F.
        • et al.
        The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double-blind, controlled study.
        Anaesthesia. 2014; 69: 46-52
        • Remérand F.
        • Tendre C.L.
        • Baud A.
        • Couvret C.
        • Pourrat X.
        • Favard L.
        • et al.
        The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study.
        Anesth Analg. 2009; 109: 1963-1971
        • Tan T.L.
        • Longenecker A.S.
        • Rhee J.H.
        • Good R.P.
        • Emper W.D.
        • Freedman K.B.
        • et al.
        Intraoperative ketamine in total knee arthroplasty does not decrease pain and narcotic consumption: a prospective randomized controlled trial.
        J Arthroplast. 2019; 34: 1640-1645
        • Mustafa R.A.
        • Santesso N.
        • Brozek J.
        • Akl E.A.
        • Walter S.D.
        • Norman G.
        • et al.
        The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses.
        J Clin Epidemiol. 2013; 66 (quiz 742.e1-5): 736-742
        • Perrin S.B.
        • Purcell A.N.
        Intraoperative ketamine may influence persistent pain following knee arthroplasty under combined general and spinal anaesthesia: a pilot study.
        Anaesth Intensive Care. 2008; 37: 248-253
        • DeVito N.J.
        • Goldacre B.
        Catalogue of bias: publication bias.
        BMJ Evid Based Med. 2018; 24: 53-54
        • Pitrou I.
        • Boutron I.
        • Ahmad N.
        • Ravaud P.
        Reporting of safety results in published reports of randomized controlled trials.
        Arch Intern Med. 2009; 169: 1756
        • Goldhahn S.
        • Sawaguchi T.
        • Audigé L.
        • Mundi R.
        • Hanson B.
        • Bhandari M.
        • et al.
        Complication reporting in orthopaedic trials. A systematic review of randomized controlled trials.
        J Bone Joint Surg Am. 2009; 91: 1847-1853
        • Weinstein S.M.
        • Poultsides L.
        • Baaklini L.R.
        • Mörwald E.E.
        • Cozowicz C.
        • Saleh J.N.
        • et al.
        Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors.
        Br J Anaesth. 2018; 120: 999-1008
        • Memtsoudis S.
        • Cozowicz C.
        • Zubizarreta N.
        • Weinstein S.M.
        • Liu J.
        • Kim D.H.
        • et al.
        Risk factors for postoperative delirium in patients undergoing lower extremity joint arthroplasty: a retrospective population-based cohort study.
        Reg Anesth Pain Med. 2019; 44: 934
        • Avidan M.S.
        • Maybrier H.R.
        • Abdallah A.B.
        • Jacobsohn E.
        • Vlisides P.E.
        • Pryor K.O.
        • et al.
        Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.
        Lancet. 2017; 390: 267-275
        • Brinck E.C.
        • Tiippana E.
        • Heesen M.
        • Bell R.F.
        • Straube S.
        • Moore R.A.
        • et al.
        Perioperative intravenous ketamine for acute postoperative pain in adults.
        Cochrane Database Syst Rev. 2018; 12: CD012033