Peri-operative steroids reduce pain, inflammatory response and hospitalisation length following knee arthroplasty without increased risk of acute complications: a meta-analysis

  • Davide Previtali
  • Giorgio Di Laura FratturaEmail author
  • Giuseppe Filardo
  • Marco Delcogliano
  • Luca Deabate
  • Christian Candrian



There is no consensus regarding the risks and benefits of peri-operative steroid supplementation in total knee arthroplasty (TKA). The aim of this meta-analysis is to compare TKA protocols implemented with or without steroids in terms of pain, inflammatory response, hospitalisation length, and complications.


A systematic literature search was performed on July 2019 in PubMed, Medline, Embase, Web of Science, Cochrane library, and the grey literature for a meta-analysis of RCTs comparing peri-operative analgesia protocols implemented with or without steroids. Sub-analyses considering the administration route, steroid type, and dosage were performed. The inverse variance method and the Mantel–Haenszel test were used for pooling continuous variables and for dichotomous variables, respectively. Risk of bias and quality of evidence were defined according to the Cochrane guidelines.


Twenty articles were included. Steroid supplementation provides significantly lower post-operative pain from day 1 to day 4 (p < 0.05), with less opioid consumption (p = 0.05), less nausea and vomiting (p < 0.05), and greater knee range of motion (p < 0.001), thus resulting in a shorter hospitalisation length (p = 0.01). Moreover, lower C-reactive protein (p < 0.05), and IL-6 (p < 0.05) levels, but a higher blood glucose level at day 1 (p = 0.004), were documented. No significant differences were documented in all the outcomes after 4 days of follow-up. These results were achieved without an increased incidence of complications. According to the results of the sub-analyses, the intravenous administration of 200 steroid equivalents of a long-acting steroid was associated with better results.


Steroid supplementation of peri-operative drug protocols is effective in decreasing post-operative pain, opioid consumption, nausea and vomiting, range of motion limitation, and inflammatory markers without increasing short- and mid-term complications. Although these benefits last only the peri-operative period, steroid supplementation can reduce the length of hospitalisation after TKA.

Level of evidence

Systematic review and meta-analysis, level II.


TKA Prosthesis Total knee replacement Steroid Post-operative pain Hospitalisation 



Total knee arthroplasty




Randomised controlled trial


Preferred Reporting Items for Systematic Reviews and Meta-Analyses


Patient reported outcome measures


Post-operative nausea and vomit


Range of motion


Mean difference


Risk ratio




Post-operative day


Steroids equivalents



We would like to thank Guido Ascenso for the help with the English version of the manuscript.

Author contributions

DP conceived the methods of the study, performed the database search, the article selection and data extraction processes, performed the statistical analysis and drafted the manuscript. GDLF conceived the methods of the study, performed the database search, the article selection and data extraction processes, and drafted the manuscript. GF conceived the methods of the study, helped with the data extraction process, and drafted the manuscript. LD, MD, and CC helped to draft the manuscript. All authors read and approved the manuscript.

Compliance with ethical standards

Conflict of interest

Dr. Previtali, Dr. Di Laura Frattura, Dr. Deabate and Dr. Delcogliano declare they have no conflict of interest. Dr. Filardo reports institutional support from Finceramica Faenza SPA, Fidia Farmaceutici SPA, CartiHeal (2009) ltd, EON medical SRL, IGEA clinical biophysics, BIOMET, and Kensey nash outside the submitted work. Dr. Candrian reports grants from Medacta International SA, Johnson & Johnson, Lima Corporate, Zimmer Biomet, and Oped AG, outside the submitted work.


No funding were avaliable for this study.

Ethical approval

This meta-analysis and all the included studies meet all the ethical standards described in the declaration of Helsinki. No ethical commitee approval was required for this study.


  1. 1.
    Andersen KV, Nikolajsen L, Daugaard H, Andersen NT, Haraldsted V, Søballe K (2015) Local infiltration analgesia is not improved by postoperative intra-articular bolus injections for pain after total hip arthroplasty: a randomized, double-blind, placebo-controlled study with 80 patients. Acta Orthop 86:647–653Google Scholar
  2. 2.
    Backes JR, Bentley JC, Politi JR, Chambers BT (2013) Dexamethasone reduces length of hospitalization and improves postoperative pain and nausea after total joint arthroplasty: a prospective, randomized controlled trial. J Arthroplast 28:11–17CrossRefGoogle Scholar
  3. 3.
    Barletta JF (2012) Clinical and economic burden of opioid use for postsurgical pain: focus on ventilatory impairment and ileus. Pharmacotherapy 32:12S–18SCrossRefGoogle Scholar
  4. 4.
    Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P (2012) What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ Open 2:e000435CrossRefGoogle Scholar
  5. 5.
    Caldwell JR (1996) Intra-articular corticosteroids. Drugs 52:507–514CrossRefGoogle Scholar
  6. 6.
    Chai X, Liu H, You C, Wang C (2019) Efficacy of additional corticosteroid in a multimodal cocktail for postoperative analgesia following total knee arthroplasty: a meta-analysis of randomized controlled trials. Pain Pract 19:316–327CrossRefGoogle Scholar
  7. 7.
    Cheng BLY, So EHK, Hui GKM, Yung BPK, Tsui ASK, Wang OKF et al (2019) Pre-operative intravenous steroid improves pain and joint mobility after total knee arthroplasty in Chinese population: a double-blind randomized controlled trial. Eur J Orthop Surg Traumatol. Google Scholar
  8. 8.
    Chia SK, Wernecke GC, Harris IA, Bohm MT, Chen DB, MacDessi SJ (2013) Peri-articular steroid injection in total knee arthroplasty: a prospective, double blinded, randomized controlled trial. J Arthroplast 28:620–623CrossRefGoogle Scholar
  9. 9.
    Christensen CP, Jacobs CA, Jennings HR (2009) Effect of periarticular corticosteroid injections during total knee arthroplasty: a double-blind randomized trial. J Bone Jt Surg Am 91:2550–2555CrossRefGoogle Scholar
  10. 10.
    Cui Z, Liu X, Teng Y, Jiang J, Wang J, Xia Y (2015) The efficacy of steroid injection in total knee or hip arthroplasty. Knee Surg Sports Traumatol Arthrosc 23:2306–2314CrossRefGoogle Scholar
  11. 11.
    Dissanayake R, Du HN, Robertson IK, Ogden K, Wiltshire K, Mulford JS (2018) Does dexamethasone reduce hospital readiness for discharge, pain, nausea, and early patient satisfaction in hip and knee arthroplasty? A randomized, controlled trial. J Arthroplast 33:3429–3436CrossRefGoogle Scholar
  12. 12.
    Fan Z, Ma J, Kuang M, Zhang L, Han B, Yang B et al (2018) The efficacy of dexamethasone reducing postoperative pain and emesis after total knee arthroplasty: a systematic review and meta-analysis. Int J Surg 52:149–155CrossRefGoogle Scholar
  13. 13.
    Grosu I, Lavand’homme P, Thienpont E (2014) Pain after knee arthroplasty: an unresolved issue. Knee Surg Sports Traumatol Arthrosc 22:1744–1758CrossRefGoogle Scholar
  14. 14.
    Habib G, Safia A (2009) The effect of intra-articular injection of betamethasone acetate/betamethasone sodium phosphate on blood glucose levels in controlled diabetic patients with symptomatic osteoarthritis of the knee. Clin Rheumatol 28:85–87CrossRefGoogle Scholar
  15. 15.
    Habib GS, Saliba W, Nashashibi M (2010) Local effects of intra-articular corticosteroids. Clin Rheumatol 29:347–356CrossRefGoogle Scholar
  16. 16.
    Halawi MJ, Grant SA, Bolognesi MP (2015) Multimodal analgesia for total joint arthroplasty. Orthopedics 38:e616–e625CrossRefGoogle Scholar
  17. 17.
    Higgins J, Sterne J, Savović J, Page M, Hróbjartsson A, Boutron I et al (2016) A revised tool for assessing risk of bias in randomized trials. Cochrane Database Syst Rev 10:29–31Google Scholar
  18. 18.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefGoogle Scholar
  19. 19.
    Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13CrossRefGoogle Scholar
  20. 20.
    Husted H, Lunn TH, Troelsen A, Gaarn-Larsen L, Kristensen BB, Kehlet H (2011) Why still in hospital after fast-track hip and knee arthroplasty? Acta Orthop 82:679–684CrossRefGoogle Scholar
  21. 21.
    Ikeuchi M, Kamimoto Y, Izumi M, Fukunaga K, Aso K, Sugimura N et al (2014) Effects of dexamethasone on local infiltration analgesia in total knee arthroplasty: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc 22:1638–1643CrossRefGoogle Scholar
  22. 22.
    Jaeger P, Zaric D, Fomsgaard JS, Hilsted KL, Bjerregaard J, Gyrn J et al (2013) Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty: a randomized, double-blind study. Reg Anesth Pain Med 38:526–532CrossRefGoogle Scholar
  23. 23.
    Kadic AJ, Vucic K, Dosenovic S, Sapunar D, Puljak L (2016) Extracting data from figures with software was faster, with higher interrater reliability than manual extraction. J Clin Epidemiol 74:119–123CrossRefGoogle Scholar
  24. 24.
    Kehlet H (2013) Fast-track hip and knee arthroplasty. Lancet 381:1600–1602CrossRefGoogle Scholar
  25. 25.
    Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP et al (2014) Reduced short-term complications and mortality following enhanced recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop 85:26–31CrossRefGoogle Scholar
  26. 26.
    Kim DH, Pearson-Chauhan KM, McCarthy RJ, Buvanendran A (2018) Predictive factors for developing chronic pain after total knee arthroplasty. J Arthroplast 33:3372–3378CrossRefGoogle Scholar
  27. 27.
    Kim TW, Park SJ, Lim SH, Seong SC, Lee S, Lee MC (2015) Which analgesic mixture is appropriate for periarticular injection after total knee arthroplasty? Prospective, randomized, double-blind study. Knee Surg Sports Traumatol Arthrosc 23:838–845CrossRefGoogle Scholar
  28. 28.
    Koh IJ, Chang CB, Lee JH, Jeon Y-T, Kim TK (2013) Preemptive low-dose dexamethasone reduces postoperative emesis and pain after TKA: a randomized controlled study. Clin Orthop Relat Res 471:3010–3020CrossRefGoogle Scholar
  29. 29.
    Li D, Tan Z, Kang P, Shen B, Pei F (2017) Effects of multi-site infiltration analgesia on pain management and early rehabilitation compared with femoral nerve or adductor canal block for patients undergoing total knee arthroplasty: a prospective randomized controlled trial. Int Orthop 41:75–83CrossRefGoogle Scholar
  30. 30.
    Li D, Zhao J, Yang Z, Kang P, Shen B, Pei F (2019) Multiple low doses of intravenous corticosteroids to improve early rehabilitation in total knee arthroplasty: a randomized clinical trial. J Knee Surg 32:171–179CrossRefGoogle Scholar
  31. 31.
    Li X, Xu G, Xie W, Ma S (2018) The efficacy and safety of dexamethasone for pain management after total knee arthroplasty: a systematic review and meta-analysis. Int J Surg 53:65–71CrossRefGoogle Scholar
  32. 32.
    Lindberg-Larsen V, Bandholm TQ, Zilmer CK, Bagger J, Hornsleth M, Kehlet H (2017) Preoperative methylprednisolone does not reduce loss of knee-extension strength after total knee arthroplasty: a randomized, double-blind, placebo-controlled trial of 61 patients. Acta Orthop 88:543–549CrossRefGoogle Scholar
  33. 33.
    Lindberg-Larsen V, Ostrowski S, Lindberg-Larsen M, Rovsing M, Johansson P, Kehlet H (2017) The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial. Anaesthesia 72:1217–1224CrossRefGoogle Scholar
  34. 34.
    Luna IE, Kehlet H, Jensen CM, Christiansen TG, Lind T, Stephensen SL et al (2017) The effect of preoperative intra-articular methylprednisolone on pain after TKA: a randomized double-blinded placebo controlled trial in patients with high-pain knee osteoarthritis and sensitization. J Pain 18:1476–1487CrossRefGoogle Scholar
  35. 35.
    Lunn TH, Kristensen BB, Andersen L, Husted H, Otte K, Gaarn-Larsen L et al (2010) Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial. Br J Anaesth 106:230–238CrossRefGoogle Scholar
  36. 36.
    McLawhorn AS, Beathe J, YaDeau J, Buschiazzo V, Purdue PE, Ma Y et al (2015) Effects of steroids on thrombogenic markers in patients undergoing unilateral total knee arthroplasty: a prospective, double-blind, randomized controlled trial. J Orthop Res 33:412–416CrossRefGoogle Scholar
  37. 37.
    Meissner W, Coluzzi F, Fletcher D, Huygen F, Morlion B, Neugebauer E et al (2015) Improving the management of post-operative acute pain: priorities for change. Curr Med Res Opin 31:2131–2143CrossRefGoogle Scholar
  38. 38.
    Mohammad HR, Hamilton TW, Strickland L, Trivella M, Murray D, Pandit H (2018) Perioperative adjuvant corticosteroids for postoperative analgesia in knee arthroplasty: a meta-analysis of 1,396 knees. Acta Orthop 89:71–76CrossRefGoogle Scholar
  39. 39.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269CrossRefGoogle Scholar
  40. 40.
    Pabinger C, Lothaller H, Geissler A (2015) Utilization rates of knee-arthroplasty in OECD countries. Osteoarthr Cartil 23:1664–1673CrossRefGoogle Scholar
  41. 41.
    Ryan R, Hill S (2016) How to GRADE the quality of the evidence. Cochrane Consumers and Communication Group. Version 3.0. Accessed Dec 2016
  42. 42.
    Rytter S, Stilling M, Munk S, Hansen TB (2017) Methylprednisolone reduces pain and decreases knee swelling in the first 24 h after fast-track unicompartmental knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 25:284–290CrossRefGoogle Scholar
  43. 43.
    Seah V, Chin P, Chia S, Yang K, Lo N, Yeo S (2011) Single-dose periarticular steroid infiltration for pain management in total knee arthroplasty: a prospective, double-blind, randomised controlled trial. Singap Med J 52:19–23Google Scholar
  44. 44.
    Thomazeau J, Rouquette A, Martinez V, Rabuel C, Prince N, Laplanche JL et al (2016) Predictive factors of chronic post-surgical pain at 6 months following knee replacement: influence of postoperative pain trajectory and genetics. Pain Phys 19:E729–E741Google Scholar
  45. 45.
    Tsukada S, Wakui M, Hoshino A (2016) The impact of including corticosteroid in a periarticular injection for pain control after total knee arthroplasty: a double-blind randomised controlled trial. Bone Jt J 98:194–200CrossRefGoogle Scholar
  46. 46.
    Vucic K, Kadic AJ, Puljak L (2015) Survey of Cochrane protocols found methods for data extraction from figures not mentioned or unclear. J Clin Epidemiol 68:1161–1164CrossRefGoogle Scholar
  47. 47.
    Wu Y, Lu X, Ma Y, Zeng Y, Bao X, Xiong H et al (2018) Perioperative multiple low-dose dexamethasones improves postoperative clinical outcomes after Total knee arthroplasty. BMC Musculoskelet Disord 19:428CrossRefGoogle Scholar
  48. 48.
    Xu B, Ma J, Huang Q, Huang Z-y, Zhang S-y, Pei F-x (2018) Two doses of low-dose perioperative dexamethasone improve the clinical outcome after total knee arthroplasty: a randomized controlled study. Knee Surg Sports Traumatol Arthrosc 26:1549–1556CrossRefGoogle Scholar
  49. 49.
    Xu H, Zhang S, Xie J, Lei Y, Cao G, Pei F (2018) Multiple doses of perioperative dexamethasone further improve clinical outcomes after total knee arthroplasty: a prospective, randomized, controlled study. J Arthroplast 33:3448–3454CrossRefGoogle Scholar
  50. 50.
    Yue D-B, Wang B-L, Liu K-P, Guo W-S (2013) Efficacy of multimodal cocktail periarticular injection with or without steroid in total knee arthroplasty. Chin Med J 126:3851–3855Google Scholar
  51. 51.
    Zhou G, Ma L, Jing J, Jiang H (2018) A meta-analysis of dexamethasone for pain management in patients with total knee arthroplasty. Medicine (Baltimore) 97(35):e11753. CrossRefGoogle Scholar

Copyright information

© European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2019

Authors and Affiliations

  1. 1.Orthopaedic and Traumatology UnitOspedale Regionale di Lugano, EOCLuganoSwitzerland
  2. 2.ATRCIRCCS Istituto Ortopedico RizzoliBolognaItaly

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