[Skip to Content]
[Skip to Content Landing]
Figure 1.
Pain Relief and Analgesic Consumption
Pain Relief and Analgesic Consumption

Shown are individual and pooled weighted mean differences in pain measured with a visual analog scale using the inverse variance method. A, The mean differences at 1, 2, and 6 months after surgery.63,65 B, The mean differences at 2 days and 8 days after surgery.66-68 A random-effects model was used to pool the data.

Figure 2.
Opioid and Other Analgesic Consumption
Opioid and Other Analgesic Consumption

Shown are individual and pooled weighted mean differences in opioid consumption within 48 hours after surgery (morphine equivalents in milligrams per kilogram per 48 hours) using the inverse variance method. A, Electrotherapy.48,64 B, Cryotherapy.48,53,55,56,59,61,62 A random-effects model was used to pool the data.

Table 1.  
Characteristics of Randomized Clinical Trials of Nonpharmacological Postoperative Pain Management After Total Knee Arthroplasty
Characteristics of Randomized Clinical Trials of Nonpharmacological Postoperative Pain Management After Total Knee Arthroplasty
Table 2.  
Main Findings of the Meta-analysis of Nonpharmacological Postoperative Pain Management After Total Knee Arthroplastya
Main Findings of the Meta-analysis of Nonpharmacological Postoperative Pain Management After Total Knee Arthroplastya
Supplement.

eTable 1. Risk of Bias Summary From Randomized Clinical Trials for Non-Pharmacological Postoperative Pain Management After Total Knee Arthroplasty

eTable 2. GRADE of Evidence Assessment for Non-Pharmacological Postoperative Pain Management After Total Knee Arthroplasty

eTable 3. Summary of Key Review Findings for Non-Pharmacological Postoperative Pain Management After Total Knee Arthroplasty

eFigure 1. PRISMA Flowchart Depicting the Search Strategy

eFigure 2. Pain Relief: Cryotherapy

eFigure 3. Pain Relief: Continuous Passive Motion (CPM)

eFigure 4. Pain Relief: Continuous Passive Motion (CPM)

eFigure 5. Pain Relief: Preoperative Exercise

eFigure 6. NSAID Consumption: Cryotherapy

eFigure 7. Opioid Consumption: Acupuncture

eFigure 8. Opioid Consumption: Continuous Passive Motion (CPM)

eFigure 9. Acupuncture

eFigure 10. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 11. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 12. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 13. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 14. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 15. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 16. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 17. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 18. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 19. Subgroup Sensitivity Analysis Comparing Studies Based on Allocation Concealment and Random Sequence Generation

eFigure 20. Subgroup Sensitivity Analysis Comparing Studies Based on How Pain Outcome Was Considered (Either Primary or Secondary)

eFigure 21. Subgroup Sensitivity Analysis Comparing Studies Based on How Pain Outcome Was Considered (Either Primary or Secondary)

eFigure 22. Subgroup Sensitivity Analysis Comparing Studies Based on How Pain Outcome Was Considered (Either Primary or Secondary)

eFigure 23. Subgroup Sensitivity Analysis Comparing Studies Based on How Pain Outcome Was Considered (Either Primary or Secondary)

eFigure 24. Funnel Plot of Comparison for CPM Trials Measured in Terms of Reported Points in the VAS Scale at 1 Week

eFigure 25. Funnel Plot of Comparison for CPM Trials Measured in Terms of Opioid Consumption (mg/kg/48 Hours of Morphine Equivalent)

eFigure 26. Funnel Plot of Comparison for Cryotherapy Trials Measured in Terms of Reported Points in the VAS Scale

eFigure 27. Funnel Plot of Comparison for Cryotherapy Trials Measured in Terms of Opioid Consumption (mg/kg/48 Hours of Morphine Equivalent)

eFigure 28. Funnel Plot of Comparison for Electrotherapy Trials Measured in Terms of Reported Points in the VAS Scale at 1 Week

eFigure 29. Funnel Plot of Comparison for Acupuncture Trials Measured in Terms of Reported Points in the VAS Scale at 1 Week

eFigure 30. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 31. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 32. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 33. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 34. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 35. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 36. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 37. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 38. Subgroup Sensitivity Analysis Comparing Studies by Type of Control

eFigure 39. Subgroup Sensitivity Analysis Comparing Studies by Time (Studies Divided If Published Prior or Comprising Year 2000 or From 2001 Onwards)

eFigure 40. Subgroup Sensitivity Analysis Comparing Studies by Time (Studies Divided If Published Prior or Comprising Year 2000 or From 2001 Onwards)

eFigure 41. Results of the Meta-Regression for the Distribution of Age in the Groups (Treatment vs Control)

eFigure 42. Results of the Meta-Regression for the Distribution of Sex in the Groups (Treatment vs Control)

1.
Weiser  TG, Regenbogen  SE, Thompson  KD,  et al.  An estimation of the global volume of surgery: a modelling strategy based on available data.  Lancet. 2008;372(9633):139-144.PubMedGoogle ScholarCrossref
2.
Apfelbaum  JL, Chen  C, Mehta  SS, Gan  TJ.  Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged.  Anesth Analg. 2003;97(2):534-540.PubMedGoogle ScholarCrossref
3.
Joshi  GP, Ogunnaike  BO.  Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain.  Anesthesiol Clin North America. 2005;23(1):21-36.PubMedGoogle ScholarCrossref
4.
Kehlet  H, Jensen  TS, Woolf  CJ.  Persistent postsurgical pain: risk factors and prevention.  Lancet. 2006;367(9522):1618-1625.PubMedGoogle ScholarCrossref
5.
Doctor  J, Cowan  P, Meeker  D, Bruckenthal  P, Broderick  J. Encouraging integrative, non-opioid approaches to pain: a policy agenda. http://healthaffairs.org/blog/2016/10/04/encouraging-integrative-non-opioid-approaches-to-pain-a-policy-agenda/. Accessed November 17, 2016.
6.
Kerr  DR, Kohan  L.  Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients.  Acta Orthop. 2008;79(2):174-183.PubMedGoogle ScholarCrossref
7.
Zukowski  M, Kotfis  K.  The use of opioid adjuvants in perioperative multimodal analgesia.  Anaesthesiol Intensive Ther. 2012;44(1):42-46.PubMedGoogle Scholar
8.
Chughtai  M, Elmallah  RD, Mistry  JB,  et al.  Nonpharmacologic pain management and muscle strengthening following total knee arthroplasty.  J Knee Surg. 2016;29(3):194-200.PubMedGoogle ScholarCrossref
9.
Shakespeare  D, Kinzel  V.  Rehabilitation after total knee replacement: time to go home?  Knee. 2005;12(3):185-189.PubMedGoogle ScholarCrossref
10.
Mascarin  NC, Vancini  RL, Andrade  ML, Magalhães  EP, de Lira  CA, Coimbra  IB.  Effects of kinesiotherapy, ultrasound and electrotherapy in management of bilateral knee osteoarthritis: prospective clinical trial.  BMC Musculoskelet Disord. 2012;13(13):182.PubMedGoogle ScholarCrossref
11.
Harvey  LA, Brosseau  L, Herbert  RD.  Continuous passive motion following total knee arthroplasty in people with arthritis.  Cochrane Database Syst Rev. 2014;(2):CD004260.PubMedGoogle Scholar
12.
Abbasi  J.  As opioid epidemic rages, complementary health approaches to pain gain traction.  JAMA. 2016;316(22):2343-2344.PubMedGoogle ScholarCrossref
13.
Brander  V, Stulberg  SD.  Rehabilitation after hip- and knee-joint replacement: an experience- and evidence-based approach to care.  Am J Phys Med Rehabil. 2006;85(11)(suppl):S98-S118.PubMedGoogle ScholarCrossref
14.
Beswick  AD, Wylde  V, Gooberman-Hill  R, Blom  A, Dieppe  P.  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. 2012;2(1):e000435-e000435.PubMedGoogle ScholarCrossref
15.
Puolakka  PA, Rorarius  MG, Roviola  M, Puolakka  TJ, Nordhausen  K, Lindgren  L.  Persistent pain following knee arthroplasty.  Eur J Anaesthesiol. 2010;27(5):455-460.PubMedGoogle ScholarCrossref
16.
Crespin  DJ, Griffin  KH, Johnson  JR,  et al.  Acupuncture provides short-term pain relief for patients in a total joint replacement program.  Pain Med. 2015;16(6):1195-1203.PubMedGoogle ScholarCrossref
17.
McCartney  CJ, Nelligan  K.  Postoperative pain management after total knee arthroplasty in elderly patients: treatment options.  Drugs Aging. 2014;31(2):83-91.PubMedGoogle ScholarCrossref
18.
Liberati  A, Altman  DG, Tetzlaff  J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.  J Clin Epidemiol. 2009;62(10):e1-e34.PubMedGoogle ScholarCrossref
19.
Gori  D, Tedesco  D, Fantini  MP, Hernandez-Boussard  T, Desai  K, Bianciardi  L. Non-pharmaceutical interventions in post-operative pain management of total knee replacement. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016052104. Accessed November 28, 2016.
20.
Greenhalgh  T, Peacock  R.  Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources.  BMJ. 2005;331(7524):1064-1065.PubMedGoogle ScholarCrossref
21.
Sheppard  MS, Westlake  SM, McQuarrie  A.  Continuous passive motion: where are we now?  Physiother Can. 1995;47(1):36-39.Google Scholar
22.
Beaupré  LA, Lier  D, Davies  DM, Johnston  DB.  The effect of a preoperative exercise and education program on functional recovery, health related quality of life, and health service utilization following primary total knee arthroplasty.  J Rheumatol. 2004;31(6):1166-1173.PubMedGoogle Scholar
23.
Adie  S, Kwan  A, Naylor  JM, Harris  IA, Mittal  R.  Cryotherapy following total knee replacement.  Cochrane Database Syst Rev. 2012;(9):CD007911.PubMedGoogle Scholar
24.
Watson  T.  Key concepts with electrophysical agents.  Phys Ther Rev. 2010;15(4):351-359.Google ScholarCrossref
25.
Sims  J.  The mechanism of acupuncture analgesia: a review.  Complement Ther Med. 1997;5(2):102-111. doi:10.1016/S0965-2299(97)80008-8Google ScholarCrossref
26.
Harris  RE, Zubieta  JK, Scott  DJ, Napadow  V, Gracely  RH, Clauw  DJ.  Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on µ-opioid receptors (MORs).  Neuroimage. 2009;47(3):1077-1085.PubMedGoogle ScholarCrossref
27.
Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. http://handbook.cochrane.org. Updated March 2011. Accessed July 10, 2016.
28.
Guyatt  GH, Oxman  AD, Schünemann  HJ, Tugwell  P, Knottnerus  A.  GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology J Clin Epidemiol. 2011;64(4):380-382.PubMedGoogle ScholarCrossref
29.
Furlan  AD, Malmivaara  A, Chou  R,  et al; Editorial Board of the Cochrane Back, Neck Group.  2015 Updated Method Guideline for Systematic Reviews in the Cochrane Back and Neck Group.  Spine (Phila Pa 1976). 2015;40(21):1660-1673.PubMedGoogle ScholarCrossref
30.
DerSimonian  R, Laird  N.  Meta-analysis in clinical trials.  Control Clin Trials. 1986;7(3):177-188.PubMedGoogle ScholarCrossref
31.
Beaupré  LA, Davies  DM, Jones  CA, Cinats  JG.  Exercise combined with continuous passive motion or slider board therapy compared with exercise only: a randomized controlled trial of patients following total knee arthroplasty.  Phys Ther. 2001;81(4):1029-1037.PubMedGoogle Scholar
32.
Bennett  LA, Brearley  SC, Hart  JA, Bailey  MJ.  A comparison of 2 continuous passive motion protocols after total knee arthroplasty: a controlled and randomized study.  J Arthroplasty. 2005;20(2):225-233.PubMedGoogle ScholarCrossref
33.
Bruun-Olsen  V, Heiberg  KE, Mengshoel  AM.  Continuous passive motion as an adjunct to active exercises in early rehabilitation following total knee arthroplasty: a randomized controlled trial.  Disabil Rehabil. 2009;31(4):277-283.PubMedGoogle ScholarCrossref
34.
Chen  LH, Chen  CH, Lin  SY,  et al.  Aggressive continuous passive motion exercise does not improve knee range of motion after total knee arthroplasty.  J Clin Nurs. 2013;22(3-4):389-394.PubMedGoogle ScholarCrossref
35.
Colwell  CW  Jr, Morris  BA.  The influence of continuous passive motion on the results of total knee arthroplasty.  Clin Orthop Relat Res. 1992;(276):225-228.PubMedGoogle Scholar
36.
Denis  M, Moffet  H, Caron  F, Ouellet  D, Paquet  J, Nolet  L.  Effectiveness of continuous passive motion and conventional physical therapy after total knee arthroplasty: a randomized clinical trial.  Phys Ther. 2006;86(2):174-185.PubMedGoogle Scholar
37.
Harms  M, Engstrom  B.  Continuous passive motion as an adjunct to treatment in the physiotherapy management of the total knee arthroplasty patient.  Physiotherapy. 1991;77(4):301-307. doi:10.1016/S0031-9406(10)61768-3Google ScholarCrossref
38.
Kim  TK, Park  KK, Yoon  SW, Kim  SJ, Chang  CB, Seong  SC.  Clinical value of regular passive ROM exercise by a physical therapist after total knee arthroplasty.  Knee Surg Sports Traumatol Arthrosc. 2009;17(10):1152-1158.PubMedGoogle ScholarCrossref
39.
Lenssen  A, de Bie  RA, Bulstra  SK, van Steyn  MJA.  Continuous passive motion (CPM) in rehabilitation following total knee arthroplasty: a randomised controlled trial.  Phys Ther Rev. 2003;(8):123-129. doi:10.1179/108331903225003019Google Scholar
40.
Lenssen  TA, van Steyn  MJ, Crijns  YH,  et al.  Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.  BMC Musculoskelet Disord. 2008;9:60.PubMedGoogle ScholarCrossref
41.
MacDonald  SJ, Bourne  RB, Rorabeck  CH, McCalden  RW, Kramer  J, Vaz  M.  Prospective randomized clinical trial of continuous passive motion after total knee arthroplasty.  Clin Orthop Relat Res. 2000;(380):30-35.PubMedGoogle Scholar
42.
Maniar  RN, Baviskar  JV, Singhi  T, Rathi  SS.  To use or not to use continuous passive motion post–total knee arthroplasty presenting functional assessment results in early recovery.  J Arthroplasty. 2012;27(2):193-200.e1.PubMedGoogle ScholarCrossref
43.
May  LA, Busse  W, Zayac  D, Whitridge  MR.  Comparison of continuous passive motion (CPM) machines and lower limb mobility boards (LLiMB) in the rehabilitation of patients with total knee arthroplasty.  Can J Rehabil. 1999;12:257-263.Google Scholar
44.
McInnes  J, Larson  MG, Daltroy  LH,  et al.  A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.  JAMA. 1992;268(11):1423-1428.PubMedGoogle ScholarCrossref
45.
Montgomery  F, Eliasson  M.  Continuous passive motion compared to active physical therapy after knee arthroplasty: similar hospitalization times in a randomized study of 68 patients.  Acta Orthop Scand. 1996;67(1):7-9.PubMedGoogle ScholarCrossref
46.
Pope  RO, Corcoran  S, McCaul  K, Howie  DW.  Continuous passive motion after primary total knee arthroplasty: does it offer any benefits?  J Bone Joint Surg Br. 1997;79(6):914-917.PubMedGoogle ScholarCrossref
47.
Sahin  E, Akalin  E, Bircan  C,  et al.  The effects of continuous passive motion on outcome in total knee arthroplasty.  J Rheumatol Med Rehabil. 2006;17(2):85-90.Google Scholar
48.
Walker  RH, Morris  BA, Angulo  DL, Schneider  J, Colwell  CW  Jr.  Postoperative use of continuous passive motion, transcutaneous electrical nerve stimulation, and continuous cooling pad following total knee arthroplasty.  J Arthroplasty. 1991;6(2):151-156.PubMedGoogle ScholarCrossref
49.
Calatayud  J, Casaña  J, Ezzatvar  Y, Jakobsen  MD, Sundstrup  E, Andersen  LL.  High-intensity preoperative training improves physical and functional recovery in the early post-operative periods after total knee arthroplasty: a randomized controlled trial [published online January 14, 2016].  Knee Surg Sports Traumatol Arthrosc. PubMedGoogle Scholar
50.
Gstoettner  M, Raschner  C, Dirnberger  E, Leimser  H, Krismer  M.  Preoperative proprioceptive training in patients with total knee arthroplasty.  Knee. 2011;18(4):265-270.PubMedGoogle ScholarCrossref
51.
McKay  C, Prapavessis  H, Doherty  T.  The effect of a prehabilitation exercise program on quadriceps strength for patients undergoing total knee arthroplasty: a randomized controlled pilot study.  PM R. 2012;4(9):647-656.PubMedGoogle ScholarCrossref
52.
Albrecht  S, le Blond  R, Köhler  V,  et al.  [Cryotherapy as analgesic technique in direct, postoperative treatment following elective joint replacement]  [in German].  Z Orthop Ihre Grenzgeb. 1997;135(1):45-51.PubMedGoogle ScholarCrossref
53.
Gibbons  CE, Solan  MC, Ricketts  DM, Patterson  M.  Cryotherapy compared with Robert Jones bandage after total knee replacement: a prospective randomized trial.  Int Orthop. 2001;25(4):250-252.PubMedGoogle ScholarCrossref
54.
Ivey  M, Johnston  RV, Uchida  T.  Cryotherapy for postoperative pain relief following knee arthroplasty.  J Arthroplasty. 1994;9(3):285-290.PubMedGoogle ScholarCrossref
55.
Kullenberg  B, Ylipää  S, Söderlund  K, Resch  S.  Postoperative cryotherapy after total knee arthroplasty: a prospective study of 86 patients.  J Arthroplasty. 2006;21(8):1175-1179.PubMedGoogle ScholarCrossref
56.
Levy  AS, Marmar  E.  The role of cold compression dressings in the postoperative treatment of total knee arthroplasty.  Clin Orthop Relat Res. 1993;(297):174-178.PubMedGoogle Scholar
57.
Morsi  E.  Continuous-flow cold therapy after total knee arthroplasty.  J Arthroplasty. 2002;17(6):718-722.PubMedGoogle ScholarCrossref
58.
Radkowski  CA, Pietrobon  R, Vail  TP, Nunley  JA  II, Jain  NB, Easley  ME.  Cryotherapy temperature differences after total knee arthroplasty: a prospective randomized trial.  J Surg Orthop Adv. 2007;16(2):67-72.PubMedGoogle Scholar
59.
Smith  J, Stevens  J, Taylor  M, Tibbey  J.  Bandaging and cold therapy in total knee replacement surgery.  Orthop Nurs. 2002;21(2):61-66.PubMedGoogle ScholarCrossref
60.
Su  EP, Perna  M, Boettner  F,  et al.  A prospective, multi-center, randomised trial to evaluate the efficacy of a cryopneumatic device on total knee arthroplasty recovery.  J Bone Joint Surg Br. 2012;94(11)(suppl A):153-156.PubMedGoogle ScholarCrossref
61.
Thienpont  E.  Does advanced cryotherapy reduce pain and narcotic consumption after knee arthroplasty?  Clin Orthop Relat Res. 2014;472(11):3417-3423.PubMedGoogle ScholarCrossref
62.
Webb  JM, Williams  D, Ivory  JP, Day  S, Williamson  DM.  The use of cold compression dressings after total knee replacement: a randomized controlled trial.  Orthopedics. 1998;21(1):59-61.PubMedGoogle Scholar
63.
Adravanti  P, Nicoletti  S, Setti  S, Ampollini  A, de Girolamo  L.  Effect of pulsed electromagnetic field therapy in patients undergoing total knee arthroplasty: a randomised controlled trial.  Int Orthop. 2014;38(2):397-403.PubMedGoogle ScholarCrossref
64.
Borckardt  JJ, Reeves  ST, Robinson  SM,  et al.  Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA).  Clin J Pain. 2013;29(11):925-928.PubMedGoogle ScholarCrossref
65.
Moretti  B, Notarnicola  A, Moretti  L,  et al.  I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study.  BMC Musculoskelet Disord. 2012;13(1):88.PubMedGoogle ScholarCrossref
66.
Chen  CC, Yang  CC, Hu  CC, Shih  HN, Chang  YH, Hsieh  PH.  Acupuncture for pain relief after total knee arthroplasty: a randomized controlled trial.  Reg Anesth Pain Med. 2015;40(1):31-36.PubMedGoogle ScholarCrossref
67.
Mikashima  Y, Takagi  T, Tomatsu  T, Horikoshi  M, Ikari  K, Momohara  S.  Efficacy of acupuncture during post-acute phase of rehabilitation after total knee arthroplasty.  J Tradit Chin Med. 2012;32(4):545-548.PubMedGoogle ScholarCrossref
68.
Tsang  RC, Tsang  PL, Ko  CY, Kong  BC, Lee  WY, Yip  HT.  Effects of acupuncture and sham acupuncture in addition to physiotherapy in patients undergoing bilateral total knee arthroplasty: a randomized controlled trial.  Clin Rehabil. 2007;21(8):719-728.PubMedGoogle ScholarCrossref
69.
Tzeng  CY, Chang  SL, Wu  CC,  et al.  Single-blinded, randomised preliminary study evaluating the effects of 2 Hz electroacupuncture for postoperative pain in patients with total knee arthroplasty.  Acupunct Med. 2015;33(4):284-288.PubMedGoogle ScholarCrossref
70.
Bjordal  JM, Johnson  MI, Ljunggreen  AE.  Transcutaneous electrical nerve stimulation (TENS) can reduce postoperative analgesic consumption: a meta-analysis with assessment of optimal treatment parameters for postoperative pain.  Eur J Pain. 2003;7(2):181-188.PubMedGoogle ScholarCrossref
71.
Joshi  RN, White  PB, Murray-Weir  M, Alexiades  MM, Sculco  TP, Ranawat  AS.  Prospective randomized trial of the efficacy of continuous passive motion post total knee arthroplasty: experience of the Hospital for Special Surgery.  J Arthroplasty. 2015;30(12):2364-2369.PubMedGoogle ScholarCrossref
72.
Cabilan  CJ, Hines  S, Munday  J.  The effectiveness of prehabilitation or preoperative exercise for surgical patients: a systematic review.  JBI Database System Rev Implement Rep. 2015;13(1):146-187.PubMedGoogle ScholarCrossref
73.
Hoogeboom  TJ, Oosting  E, Vriezekolk  JE,  et al.  Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis.  PLoS One. 2012;7(5):e38031.PubMedGoogle ScholarCrossref
74.
Santa Mina  D, Clarke  H, Ritvo  P,  et al.  Effect of total-body prehabilitation on postoperative outcomes: a systematic review and meta-analysis.  Physiotherapy. 2014;100(3):196-207.PubMedGoogle ScholarCrossref
Original Investigation
October 18, 2017

Drug-Free Interventions to Reduce Pain or Opioid Consumption After Total Knee Arthroplasty: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Medicine, Stanford University, Stanford, California
  • 2Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
  • 3Center for Innovation to Implementation, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
  • 4Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California
  • 5Department of Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
  • 6Department of Surgery, Stanford University, Stanford, California
  • 7Department of Biomedical Data Science, Stanford University, California
JAMA Surg. 2017;152(10):e172872. doi:10.1001/jamasurg.2017.2872
Key Points

Question  Which of the nonpharmacological interventions used for postoperative pain after total knee arthroplasty are effective?

Findings  In a systematic review of 5509 studies, 39 randomized clinical trials were included in a meta-analysis (2391 patients) and demonstrated moderate-certainty evidence that electrotherapy and acupuncture reduce or delay opioid consumption, but there is low certainty or very low certainty that they improve pain. Continuous passive motion and preoperative exercise do not improve pain or reduce opioid consumption (low certainty or very low certainty), and cryotherapy reduces opioid consumption but does not improve pain (very low certainty).

Meaning  After total knee arthroplasty, electrotherapy and acupuncture were associated with reduced and delayed opioid consumption.

Abstract

Importance  There is increased interest in nonpharmacological treatments to reduce pain after total knee arthroplasty. Yet, little consensus supports the effectiveness of these interventions.

Objective  To systematically review and meta-analyze evidence of nonpharmacological interventions for postoperative pain management after total knee arthroplasty.

Data Sources  Database searches of MEDLINE (PubMed), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Web of Science (ISI database), Physiotherapy Evidence (PEDRO) database, and ClinicalTrials.gov for the period between January 1946 and April 2016.

Study Selection  Randomized clinical trials comparing nonpharmacological interventions with other interventions in combination with standard care were included.

Data Extraction and Synthesis  Three reviewers independently extracted the data from selected articles using a standardized form and assessed the risk of bias. A random-effects model was used for the analyses.

Main Outcomes and Measures  Postoperative pain and consumption of opioids and analgesics.

Results  Of 5509 studies, 39 randomized clinical trials were included in the meta-analysis (2391 patients). The most commonly performed interventions included continuous passive motion, preoperative exercise, cryotherapy, electrotherapy, and acupuncture. Moderate-certainty evidence showed that electrotherapy reduced the use of opioids (mean difference, −3.50; 95% CI, −5.90 to −1.10 morphine equivalents in milligrams per kilogram per 48 hours; P = .004; I2 = 17%) and that acupuncture delayed opioid use (mean difference, 46.17; 95% CI, 20.84 to 71.50 minutes to the first patient-controlled analgesia; P < .001; I2 = 19%). There was low-certainty evidence that acupuncture improved pain (mean difference, −1.14; 95% CI, −1.90 to −0.38 on a visual analog scale at 2 days; P = .003; I2 = 0%). Very low-certainty evidence showed that cryotherapy was associated with a reduction in opioid consumption (mean difference, −0.13; 95% CI, −0.26 to −0.01 morphine equivalents in milligrams per kilogram per 48 hours; P = .03; I2 = 86%) and in pain improvement (mean difference, −0.51; 95% CI, −1.00 to −0.02 on the visual analog scale; P < .05; I2 = 62%). Low-certainty or very low-certainty evidence showed that continuous passive motion and preoperative exercise had no pain improvement and reduction in opioid consumption: for continuous passive motion, the mean differences were −0.05 (95% CI, −0.35 to 0.25) on the visual analog scale (P = .74; I2 = 52%) and 6.58 (95% CI, −6.33 to 19.49) opioid consumption at 1 and 2 weeks (P = .32, I2 = 87%), and for preoperative exercise, the mean difference was −0.14 (95% CI, −1.11 to 0.84) on the Western Ontario and McMaster Universities Arthritis Index Scale (P = .78, I2 = 65%).

Conclusions and Relevance  In this meta-analysis, electrotherapy and acupuncture after total knee arthroplasty were associated with reduced and delayed opioid consumption.

Introduction

There are 234 million major surgical procedures performed every year worldwide, and most patients experience moderate to severe postoperative pain.1,2 Inadequate postoperative pain management has profound acute effects, including immune system suppression, decreased mobility that increases deep vein thrombosis and pulmonary embolism rates, myocardial infarction, and pneumonia.3 Long-term influences of poor pain management include transition to chronic pain and prolonged narcotic consumption,4 which can result in opioid dependence, an epidemic in the United States.5

First-line therapies to treat postoperative pain are pharmacological, including anesthetics, opioids, and acetaminophen.6,7 Recently, nonpharmacological approaches to pain management aimed at reducing the use of prescription medications have increased.8 Physiotherapy is effective in treating postoperative pain and quality-of-life improvement and is standard treatment.9 However, other commonly used interventions for pain management have conflicting evidence on their effectiveness.10,11 As opioid addiction becomes a national priority,5 the importance of using effective nonpharmacological strategies for postoperative pain is now a top scientific priority.12

Total knee arthroplasty (TKA) is one of the most frequently performed surgical procedures worldwide. It is used for patients with advanced knee osteoarthritis, and the goals of surgery are to decrease pain, restore mobility and function, and improve health-related quality of life.13 Total knee arthroplasty is associated with intense postoperative pain, and many patients report moderate to severe postoperative pain past the anticipated recovery period.14 Therefore, many nonpharmaceutical therapies are performed in this population.10,11,15,16 Ensuring effective therapies for postoperative pain management is an important part of TKA care.17

We undertook a systematic review and meta-analysis to evaluate the effectiveness of commonly used drug-free interventions for pain management after TKA. We gathered evidence from randomized clinical trials (RCTs) on postoperative pain as measured by established pain metrics and reduced analgesic consumption, including opioids and nonsteroidal anti-inflammatory drugs (NSAIDs). This comprehensive analysis of nonpharmaceutical pain management therapies can inform practice and identify effective pain management regimens that could also potentially reduce the prescribing of opioids after surgery.

Methods

We conducted a systematic review and meta-analysis in accord with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).18 The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO).19

Search Strategy
Databases

In an academic medical setting, we searched electronic databases to identify relevant studies for the period between January 1946 and April 2016, including MEDLINE (PubMed), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Web of Science (ISI database), Physiotherapy Evidence (PEDRO) database, and clinicaltrials.gov. We scanned reference lists of selected reviews, original articles, and textbooks to find additional articles. We conducted a gray literature search for other documents and hand searches of key conference proceedings, journals, professional organizations’ websites, national joint replacement registries, and guideline clearing houses. Snowball technique was applied to the search strategy.20

Search Criteria

Because our aim was to be as comprehensive as possible in the systematic review, we did not place time or publication status limits to the search except for restriction to the English language. Two Chinese studies with English abstracts were considered; however, translation resources were not available to include them. We used the following search string in each database: (postoperative pain* OR postoperative pain OR post-operative pain) AND (total knee* or total knee arthroplasty OR total knee replacement OR TKA). Asterisks are used to truncate words, so that every desinence after the asterisks will be searched. To achieve the highest sensitivity, we used a combination of keywords and indexed terms (eg, PubMed Medical Subject Headings).

Patients, Interventions, Comparators, and Outcomes

Our primary search objective addressed the PICO (patients, interventions, comparators, and outcomes) question. These targets included (P) patients undergoing primary TKA, (I) nonpharmacological treatments for pain management (plus usual analgesic therapy), (C) other nonpharmacological intervention or no intervention (plus usual analgesic therapy), and (O) postoperative pain relief, and opioid and NSAID consumption.

Study Selection
Design

Postoperative pain management is generally layered, including pharmacological and nonpharmacological interventions. Hence, we selected studies comparing nonpharmacological interventions with routine pharmacological treatment either with other nonpharmacological approaches or with only routine pharmacological treatments. We restricted our meta-analysis to RCTs in which patients were 18 years or older and had elective primary surgical procedures that included all forms of fixation (cemented, hybrid, or cementless), surgical approaches (medial, lateral, parapatellar, or minimally invasive), and types of prostheses (constrained, semiconstrained, or mobile platform).

Outcomes of Interest

Three of us (D.T., D.G., and K.R.D.) independently screened all identified articles by scanning abstracts or portions of the text to determine if they met the inclusion criteria. Any disagreements were resolved through discussion and consensus between the reviewers. Postoperative pain relief was defined as the mean difference in scores on the visual analog scale (VAS) or the Western Ontario and McMaster Universities Arthritis Index Scale (WOMAC). Opioid and other analgesic consumption was evaluated in terms of the mean difference in consumption of morphine equivalents in milligrams per kilogram per 48 hours, while other analgesic consumption was evaluated as the mean difference in the number of tablets per day. Time to first request for analgesia (patient-controlled analgesia [PCA]) in the acupuncture group was defined as minutes from the end of the intervention to the first PCA.

Information about quality of life was not systematically provided in the studies. Therefore, it was not included.

Intervention

We restricted our focus to commonly studied postoperative pain interventions. These included continuous passive motion (CPM), preoperative exercise, cryotherapy, electrotherapy, and acupuncture.

Continuous passive motion consists of using an external machine to provide regular movement to the knee using a predetermined range of motion (ROM). Theoretically, the repeated movements help increase ROM, while simultaneously improving pain.21

Preoperative exercise (or prehabilitation) involves sessions performed by the patients in the weeks preceding surgery. This regimen enables them to cope better with the physical stress associated with the surgical procedure and aids postoperative rehabilitation efforts.22

Cryotherapy is based on applying cold to the surgical site either through ice bags or cooled water to minimize tissue trauma. The theory is that application of cooler substances reduces intra-articular temperatures, which interferes with the conduction of nerve signals and reduces local blood flow. These changes lead to decreased swelling and perceived pain.23

Electrotherapy (based on electrophysical agents) aims to reduce pain and improve function through an energy transfer to the body. These modalities include transcutaneous electrical nerve stimulation and pulsed electromagnetic fields.24

Acupuncture is a form of traditional Chinese medicine that requires the insertion of needles at specific points on the body to alleviate pain and other ailments. The plausible mechanism of acupuncture analgesia is its effect on the central nervous system, particularly a short-term and long-term effect on µ-opioid receptors, and consequent regulation of neurotransmitters and hormones.25,26

Study Quality Assessment

Two of us (D.T. and D.G.) independently assessed the risk of bias of included studies using the parameters defined by the Cochrane Handbook for Systematic Reviews of Interventions criteria.27 Disagreement was resolved through discussion and consensus between the reviewers. Based on the information provided from included studies, each item was recorded as low risk of bias, high risk of bias, or unclear (lack of information or unknown risk of bias).

Two of us (D.T. and D.G.) independently assessed the quality of the body of evidence for the different outcomes considered through the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, a validated and widely implemented tool to rate the quality of scientific evidence.28 According to the GRADE approach, we assessed 5 domains, grading the strength of evidence for each outcome.

Data Analysis and Synthesis

Three of us (D.T., D.G., and K.R.D.) independently extracted the data from included articles. Key information was gathered systematically using a standardized form. These variables included country, year of publication, number of participants, intervention, age, sex, study design, duration of intervention, outcome time points, statistical method, postoperative pain, opioid or analgesic consumption, and summary of the results.

For the pain scores, we standardized the results to a single scale by converting outcomes reported on a numerical rating scale to a 10-point VAS. Where possible, the results were extracted manually from the published figures. Data in other forms (ie, median, interquartile range, and mean [95% CI]) were converted to means (SDs) according to the Cochrane Handbook for Systematic Reviews of Interventions.27 If data (eg, SDs and SEs) were not presented in the original article, corresponding authors were contacted to acquire the missing data, although no responses were received. We also normalized data for pain relief and analgesic consumption, opioid and other analgesic consumption, and time before the first analgesic treatment. Specifically, all data on opioid consumption were converted to milligrams per kilogram per 48 hours, other analgesic consumption was converted to the number of tablets per day, and time before the first analgesic treatment was converted to minutes.

We examined the evidence tables for clinical (participants, interventions, controls, outcomes, and measurement tools) and methodological heterogeneity to determine whether the studies were similar enough to perform a meta-analysis.29 Where appropriate to pool the results, we used weighted mean differences for continuous data using the same measurement scales and standardized mean differences for continuous outcomes using different scales. We pooled both sets of summary statistics using the inverse variance method, which included studies from different time points, and we conducted sensitivity analyses by single time point.

We tested statistical heterogeneity to determine if it was appropriate to combine the studies for meta-analysis. We examined heterogeneity graphically using forest plots and statistically by calculating the I2 statistic, which describes the percentage of the variability in effect estimates that is due to heterogeneity rather than sampling error (chance). We considered an I2 statistic greater than 50% to be substantially heterogeneous. According to the Cochrane Handbook for Systematic Reviews of Interventions,27 in cases where the number of studies was less than 5 or studies were substantially heterogeneous, we used a random-effects model. We calculated the random-effects estimates for the corresponding statistics using the method by DerSimonian and Laird.30 Forest plots were created to display effect estimates with 95% CIs for individual trials and pooled results. For all data analysis, we used a software program (RevMan, version 5.3; The Cochrane Collaboration).

Results
Search Findings

Supplementary information is provided in eTables 1, 2, and 3 in the Supplement and in eFigures 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, and 42 in the Supplement. Our search yielded 5509 studies, of which 120 (112 from selection and 8 added by hand and snowball searching) were appropriate for further assessment. Of the 77 RCTs we read in extenso, we extracted the data from 39 RCTs for our meta-analysis (eFigure 1 in the Supplement). Included studies were published between 1991 and 2015.

Study Characteristics

A pooled total of 2391 patients were examined in the RCTs (Table 1). We categorized the 39 RCTs based on 2 outcomes (pain relief and analgesic consumption, including different measures and types) and 5 interventions, including 18 studies in the CPM group (14 on pain and 5 on analgesics), 3 studies in the preoperative exercise group (all on pain), 12 studies in the cryotherapy group (8 on pain and 10 on analgesics), 4 studies in the electrotherapy group (2 on pain and 2 on analgesics), and 4 studies in the acupuncture group (2 on pain and 3 on analgesics). One study48 recurred in 3 different categories owing to multiple comparison groups within the article. For the studies that did not provide sufficient data, we attempted to contact authors but received no response.

Quality Assessment

All studies were assessed for the risk of bias (eTable 1 in the Supplement). The methodological heterogeneity reflects the different range of interventions we examined. We identified that the highest bias in studies was due to improper or absent masking during the study (31 of 39 RCTs). In 2 studies54,58 on cryotherapy, masking was adequately achieved. Studies also showed high risk of bias for selective outcome reporting in 13 cases, particularly in those testing the effectiveness of CPM, cryotherapy, and electrotherapy RCTs.32,35,37,40,41,43,53,55,57,58,63,65,68 There was also high risk of bias due to improper or absent random sequencing methods in 8 studies.33,34,42,44,45,47,57,59 Last, a study65 in the electrotherapy group showed high risk of bias for incomplete outcome data. We conducted sensitivity subgroup analyses for all the outcomes considered, classifying for sequence generation and allocation concealment availability, and no significant differences were shown (eFigures 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 in the Supplement). The GRADE quality of evidence certainty level of evidence assessment is reported in detail below in the Assessed Outcomes and Evidence Synthesis subsection, in Table 2, and in eTable 2 in the Supplement.

Publication Bias

To address publication bias, we created funnel plots for all analyses. No asymmetric patterns were seen (eFigures 24, 25, 26, 27, 28, and 29 in the Supplement).

Interventions

The key findings of the meta-analysis are summarized in Table 2 for 2 types of pain scales and for 3 types of analgesic outcomes. Figure 1 and Figure 2 show the meta-analyses that reported statistically significant results.

Assessed Outcomes and Evidence Synthesis
Pain Relief and Analgesic Consumption

We found that the quality of evidence was of low certainty or very low certainty for pain improvement in all examined interventions (Table 2). Meta-analysis of 2 pain relief studies (189 patients) suggested a significant improvement in experimental groups vs controls with electrotherapy, with mean differences of −1.95 (95% CI, −2.68 to −1.22; P < .001; I2 = 17%) on the VAS at 1 month, −2.34 (95% CI, −4.49 to −0.19; P = .03; I2 = 94%) on the VAS at 2 months, and −2.60 (95% CI, −5.12 to −0.08; P = .04; I2 = 83%) on the VAS at 6 months (Figure 1A). Meta-analysis of 3 studies (230 patients) suggested a significant improvement in experimental groups vs controls with acupuncture, with a mean difference of −1.14 (95% CI, −1.90 to −0.38; P = .003; I2 = 0%) on the VAS at 6 months (Figure 1B). Meta-analysis of 8 studies (1383 patients) showed a mean difference with cryotherapy of −0.51 (95% CI, −1.00 to −0.02; P < .05; I2 = 62%), but all subgroup analyses showed no statistically significant mean differences (eFigure 2 in the Supplement). Meta-analysis of 9 studies (1025 patients) suggested no significant improvement in experimental groups vs controls with CPM (mean differences, −0.05; 95% CI, −0.35 to 0.25; P = .74; I2 = 52% on the VAS at 1 week and 6 months and −0.20; 95% CI, −0.62 to 0.23; P = .54; I2 = 0% on the CPM WOMAC at 6 weeks and 6 months) (eFigure 3 and eFigure 4 in the Supplement) or with preoperative exercise (mean difference, −0.14; 95% CI, −1.11 to 0.84; P = .78; I2 = 65% on the WOMAC at 6 and 12 weeks) (eFigure 5 in the Supplement).

To address possible overestimation that could originate from the study design (ie, pain as a primary or secondary outcome), we conducted sensitivity subgroup analyses. No significant differences were found (eFigures 20, 21, 22, and 23 in the Supplement).

Opioid and Other Analgesic Consumption

Meta-analysis of 2 studies (99 patients) showed moderate-certainty reduction in opioid consumption for electrotherapy (mean difference, −3.50; 95% CI, −5.90 to −1.10 opioids in milligrams per hour; P = .004; I2 = 17%) (Figure 2A). Meta-analysis of 7 studies (468 patients) showed very low-certainty reduction in opioid consumption for cryotherapy (mean difference, −0.13; 95% CI, −0.26 to −0.01 opioids in milligrams per hour; P = .03; I2 = 86%) (Figure 2B). Meta-analysis of 3 studies (363 patients) showed very low-certainty nonreduction in nonsteroidal antiinflammatory drug (NSAID) consumption for cryotherapy (mean difference, −0.75; 95% CI, −1.63 to 0.12 tablets per day; P = .09; I2 = 95%). Nevertheless, subgroup analyses showed a significant reduction in NSAID consumption, with mean differences of −1.90 (95% CI, −2.25 to −1.55 tablets per day; P < .01; I2 = not applicable) for cryotherapy vs nothing (1 study, with 60 patients) and −0.31 (95% CI, −0.55 to −0.07 tablet per day; P = .01; I2 = 0%) for cryotherapy vs compression (2 studies, with 303 patients) (eFigure 6 in the Supplement). Acupuncture (2 studies, with 123 patients) and CPM (5 studies, with 313 patients) showed no significant differences between experimental groups and controls for amount of opioid consumed after surgery, with low-certainty and very low-certainty evidence, respectively: the mean differences were −0.71 (95% CI, −1.44 to 0.02 opioids in milligrams per hour; P = .06; I2 = 64%) for acupuncture (eFigure 7 in the Supplement) and 6.58 (95% CI, −6.33, to 19.49 opioids in milligrams per hour; P = .32; I2 = 87%) for CPM (eFigure 8 in the Supplement). Preoperative exercise studies did not report data on opioid consumption.

To address opioid consumption changes across the study period, we conducted sensitivity analyses stratifying for period (before or after 2000). The results were not significant (eFigure 39 and eFigure 40 in the Supplement).

Time Before the First Analgesic Treatment

In 2 studies (124 patients), we assessed time to first PCA in the acupuncture group and found moderate-certainty evidence that acupuncture significantly increases this period (mean difference, 46.17; 95% CI, 20.84-71.50 minutes; P < .001; I2 = 19%) (eFigure 9 in the Supplement). Also, a subgroup analysis carried out in 1 study69 revealed a stronger difference in the acupuncture group compared with controls, with a mean difference of 57.90 (95% CI, 6.52-99.28 minutes; P = .006; I2 = not applicable).

Conflict of Interest of Included Studies

Authors of 7 studies reported at least 1 conflict of interest statement. Only 3 studies32,33,49 explicitly identified the funding sources (eTable 3 in the Supplement).

Discussion

This meta-analysis found moderate evidence that electrotherapy and acupuncture improved postoperative pain management and reduced opioid consumption. We found very low-certainty evidence that cryotherapy reduced opioid consumption, but there was no evidence that it improves perceived pain. The meta-analysis suggests that CPM and preoperative exercise do not help alleviate pain (measured at different time points and using different scales) or reduce opioid consumption.

Electrotherapy and acupuncture are known to reduce postoperative pain. Electrotherapy is thought to decrease pain by stimulating the pain fibers with a nonpainful stimulus that blocks painful stimuli from reaching the brain and is free of adverse effects.10 One study70 recommended electrotherapy to reduce analgesic use for various surgical procedures. Our findings suggest that electrotherapy may not only reduce early pain but also change the long-term trajectory of recovery from pain after TKA. We found evidence that electrotherapy changed pain severity at 1, 2, and 6 months, with increasing effect sizes over time. Hence, electrotherapy might be considered an effective nonpharmacological ancillary intervention to standard pharmacological therapy for long-term pain improvement. This finding is an important and underappreciated contribution to the literature that examines factors influencing the propensity to develop chronic pain after surgery, an area of significant general interest in clinical literature.4 However, because the quality of the studies analyzed for this outcome was very low, more high-quality RCTs on long-term pain improvement after electrotherapy are needed.

Our findings showed that acupuncture pain relief benefits concentrate in the early postoperative phase but are ineffective in the long run. A delay in opioid consumption can be considered a proxy of lower pain levels; high postoperative pain can lead to chronic pain.3 Our results suggest that acupuncture led to a modest delay in PCA requests, leading to possible benefits in this critical time window. Similarly, others have found that acupuncture provides significant pain improvement in patients undergoing TKA and total hip arthroplasty in the first 2 days after surgery.16 The acupuncture studies had less risk of bias than other modalities, so our conclusions regarding their benefit are more secure. If confirmed in future studies, our findings support the use of both electrotherapy and acupuncture after TKA.

We found less evidence that cryotherapy reduced opioid and NSAID consumption. While a Cochrane review article reported a small benefit of cryotherapy for pain at 2 days after surgery but not at 1 and 3 days,23 our results demonstrated very low-certainty evidence for this intervention on postoperative analgesia after TKA. More research about this intervention could focus on opioid consumption effects.

The CPM results are particularly notable. Continuous passive motion is commonly used after TKA, with the 2 proposed benefits of improved function and reduced pain. However, recent work has not shown the usefulness of CPM in improving functionality and rehabilitation.11 The RCTs included in our meta-analysis found very low-certainty evidence that CPM reduces opioid consumption during the early postoperative phase and found low-certainty or very low-certainty evidence that CPM provides no improvement in perceived pain. Our findings are consistent with a Cochrane review article that also found no benefits of CPM on function, pain, or quality of life after TKA.11 These results need to be cautiously considered because CPM is not without risk.71 Also, CPM is an expensive and time-consuming procedure.33,71 Because the results of other studies have suggested that CPM is ineffective in improving functionality11 and that CPM is associated with increased hospital length of stay,71 careful consideration should be exercised before applying this treatment.

Our study also found little evidence to support that preoperative exercise improves postoperative pain and thus adds to conflicting literature. Several studies have reported that preoperative exercise had no significant benefit in improving functionality, quality of life, or pain for patients after TKA,72,73 whereas others found that the intervention improved postoperative pain, hospital length of stay, and physical function after various surgical procedures.74 However, given the poor quality of the evidence, our results do not support the use of preoperative exercise for patients after TKA and advocate for further high-quality studies on this topic.

Limitations

Several limitations should be considered before interpreting these findings. First, for each intervention and outcome, we could only include a small number of studies in the analysis because of high heterogeneity in the timing and type of interventions. To address this issue, we pooled studies from different time points to obtain larger sample sizes, and subgroup analyses showed results similar to the overall findings (eFigures 30, 31, 32, 33, 34, 35, 36, 37, and 38 in the Supplement). Age and sex were not differently distributed in the groups (treatment vs control as shown in the meta-regressions) (eFigure 41 and eFigure 42 in the Supplement). Second, studies often showed a high risk or unclear risk of bias, which may have led to overestimations or underestimations of the reported effects. However, we assessed the quality of evidence through a validated tool and took into account the level of certainty of evidence for each outcome. Third, most studies did not achieve full masking, which also may have caused overestimation of effects in various meta-analyses conducted. Fourth, some studies lacked sufficient data to measure dispersion for the effect measurement (SD or SE). We attempted to address this problem by contacting authors but never obtained a response.

Conclusions

Although past studies8,10,11,16,23,73 have investigated individual nonpharmaceutical interventions for different postoperative outcomes after TKA, to our knowledge, this meta-analysis is the first comprehensive study to examine the most frequent treatments, adding new evidence on drug consumption. As prescription opioid use is under national scrutiny and because surgery has been identified as an avenue for addiction, it is important to recognize effective alternatives to standard pharmacological therapy, which remains the first option for treatment.5,12 Our study provides modest but clinically significant evidence that electrotherapy and acupuncture can potentially reduce and delay opioid consumption. However, strong supporting research is further needed. Evidence for other interventions, although limited by the quality of the underlying literature, had less support.

Back to top
Article Information

Accepted for Publication: April 29, 2017.

Corresponding Author: Tina Hernandez-Boussard, PhD, Department of Medicine, Stanford University, 1265 Welch Rd, Stanford, CA 94305 (boussard@stanford.edu).

Correction: This article was corrected on January 31, 2018, to fix an error in the Abstract.

Published Online: August 16, 2017. doi:10.1001/jamasurg.2017.2872

Author Contributions: Dr Hernandez-Boussard had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Tedesco, Asch, Carroll, Curtin, McDonald, Fantini, Hernandez-Boussard.

Acquisition, analysis, or interpretation of data: Tedesco, Gori, Desai, Curtin, Fantini, Hernandez-Boussard.

Drafting of the manuscript: Tedesco, Asch, Curtin.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Tedesco, Gori.

Obtained funding: Hernandez-Boussard.

Administrative, technical, or material support: Fantini, Hernandez-Boussard.

Study supervision: Asch, Carroll, Curtin, McDonald, Fantini, Hernandez-Boussard.

Conflict of Interest Disclosures: None reported.

Funding/Support: This project was supported by grant R01HS024096 from the Agency for Healthcare Research and Quality (to principal investigator Dr Hernandez-Boussard).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Weiser  TG, Regenbogen  SE, Thompson  KD,  et al.  An estimation of the global volume of surgery: a modelling strategy based on available data.  Lancet. 2008;372(9633):139-144.PubMedGoogle ScholarCrossref
2.
Apfelbaum  JL, Chen  C, Mehta  SS, Gan  TJ.  Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged.  Anesth Analg. 2003;97(2):534-540.PubMedGoogle ScholarCrossref
3.
Joshi  GP, Ogunnaike  BO.  Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain.  Anesthesiol Clin North America. 2005;23(1):21-36.PubMedGoogle ScholarCrossref
4.
Kehlet  H, Jensen  TS, Woolf  CJ.  Persistent postsurgical pain: risk factors and prevention.  Lancet. 2006;367(9522):1618-1625.PubMedGoogle ScholarCrossref
5.
Doctor  J, Cowan  P, Meeker  D, Bruckenthal  P, Broderick  J. Encouraging integrative, non-opioid approaches to pain: a policy agenda. http://healthaffairs.org/blog/2016/10/04/encouraging-integrative-non-opioid-approaches-to-pain-a-policy-agenda/. Accessed November 17, 2016.
6.
Kerr  DR, Kohan  L.  Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients.  Acta Orthop. 2008;79(2):174-183.PubMedGoogle ScholarCrossref
7.
Zukowski  M, Kotfis  K.  The use of opioid adjuvants in perioperative multimodal analgesia.  Anaesthesiol Intensive Ther. 2012;44(1):42-46.PubMedGoogle Scholar
8.
Chughtai  M, Elmallah  RD, Mistry  JB,  et al.  Nonpharmacologic pain management and muscle strengthening following total knee arthroplasty.  J Knee Surg. 2016;29(3):194-200.PubMedGoogle ScholarCrossref
9.
Shakespeare  D, Kinzel  V.  Rehabilitation after total knee replacement: time to go home?  Knee. 2005;12(3):185-189.PubMedGoogle ScholarCrossref
10.
Mascarin  NC, Vancini  RL, Andrade  ML, Magalhães  EP, de Lira  CA, Coimbra  IB.  Effects of kinesiotherapy, ultrasound and electrotherapy in management of bilateral knee osteoarthritis: prospective clinical trial.  BMC Musculoskelet Disord. 2012;13(13):182.PubMedGoogle ScholarCrossref
11.
Harvey  LA, Brosseau  L, Herbert  RD.  Continuous passive motion following total knee arthroplasty in people with arthritis.  Cochrane Database Syst Rev. 2014;(2):CD004260.PubMedGoogle Scholar
12.
Abbasi  J.  As opioid epidemic rages, complementary health approaches to pain gain traction.  JAMA. 2016;316(22):2343-2344.PubMedGoogle ScholarCrossref
13.
Brander  V, Stulberg  SD.  Rehabilitation after hip- and knee-joint replacement: an experience- and evidence-based approach to care.  Am J Phys Med Rehabil. 2006;85(11)(suppl):S98-S118.PubMedGoogle ScholarCrossref
14.
Beswick  AD, Wylde  V, Gooberman-Hill  R, Blom  A, Dieppe  P.  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. 2012;2(1):e000435-e000435.PubMedGoogle ScholarCrossref
15.
Puolakka  PA, Rorarius  MG, Roviola  M, Puolakka  TJ, Nordhausen  K, Lindgren  L.  Persistent pain following knee arthroplasty.  Eur J Anaesthesiol. 2010;27(5):455-460.PubMedGoogle ScholarCrossref
16.
Crespin  DJ, Griffin  KH, Johnson  JR,  et al.  Acupuncture provides short-term pain relief for patients in a total joint replacement program.  Pain Med. 2015;16(6):1195-1203.PubMedGoogle ScholarCrossref
17.
McCartney  CJ, Nelligan  K.  Postoperative pain management after total knee arthroplasty in elderly patients: treatment options.  Drugs Aging. 2014;31(2):83-91.PubMedGoogle ScholarCrossref
18.
Liberati  A, Altman  DG, Tetzlaff  J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.  J Clin Epidemiol. 2009;62(10):e1-e34.PubMedGoogle ScholarCrossref
19.
Gori  D, Tedesco  D, Fantini  MP, Hernandez-Boussard  T, Desai  K, Bianciardi  L. Non-pharmaceutical interventions in post-operative pain management of total knee replacement. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016052104. Accessed November 28, 2016.
20.
Greenhalgh  T, Peacock  R.  Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources.  BMJ. 2005;331(7524):1064-1065.PubMedGoogle ScholarCrossref
21.
Sheppard  MS, Westlake  SM, McQuarrie  A.  Continuous passive motion: where are we now?  Physiother Can. 1995;47(1):36-39.Google Scholar
22.
Beaupré  LA, Lier  D, Davies  DM, Johnston  DB.  The effect of a preoperative exercise and education program on functional recovery, health related quality of life, and health service utilization following primary total knee arthroplasty.  J Rheumatol. 2004;31(6):1166-1173.PubMedGoogle Scholar
23.
Adie  S, Kwan  A, Naylor  JM, Harris  IA, Mittal  R.  Cryotherapy following total knee replacement.  Cochrane Database Syst Rev. 2012;(9):CD007911.PubMedGoogle Scholar
24.
Watson  T.  Key concepts with electrophysical agents.  Phys Ther Rev. 2010;15(4):351-359.Google ScholarCrossref
25.
Sims  J.  The mechanism of acupuncture analgesia: a review.  Complement Ther Med. 1997;5(2):102-111. doi:10.1016/S0965-2299(97)80008-8Google ScholarCrossref
26.
Harris  RE, Zubieta  JK, Scott  DJ, Napadow  V, Gracely  RH, Clauw  DJ.  Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on µ-opioid receptors (MORs).  Neuroimage. 2009;47(3):1077-1085.PubMedGoogle ScholarCrossref
27.
Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. http://handbook.cochrane.org. Updated March 2011. Accessed July 10, 2016.
28.
Guyatt  GH, Oxman  AD, Schünemann  HJ, Tugwell  P, Knottnerus  A.  GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology J Clin Epidemiol. 2011;64(4):380-382.PubMedGoogle ScholarCrossref
29.
Furlan  AD, Malmivaara  A, Chou  R,  et al; Editorial Board of the Cochrane Back, Neck Group.  2015 Updated Method Guideline for Systematic Reviews in the Cochrane Back and Neck Group.  Spine (Phila Pa 1976). 2015;40(21):1660-1673.PubMedGoogle ScholarCrossref
30.
DerSimonian  R, Laird  N.  Meta-analysis in clinical trials.  Control Clin Trials. 1986;7(3):177-188.PubMedGoogle ScholarCrossref
31.
Beaupré  LA, Davies  DM, Jones  CA, Cinats  JG.  Exercise combined with continuous passive motion or slider board therapy compared with exercise only: a randomized controlled trial of patients following total knee arthroplasty.  Phys Ther. 2001;81(4):1029-1037.PubMedGoogle Scholar
32.
Bennett  LA, Brearley  SC, Hart  JA, Bailey  MJ.  A comparison of 2 continuous passive motion protocols after total knee arthroplasty: a controlled and randomized study.  J Arthroplasty. 2005;20(2):225-233.PubMedGoogle ScholarCrossref
33.
Bruun-Olsen  V, Heiberg  KE, Mengshoel  AM.  Continuous passive motion as an adjunct to active exercises in early rehabilitation following total knee arthroplasty: a randomized controlled trial.  Disabil Rehabil. 2009;31(4):277-283.PubMedGoogle ScholarCrossref
34.
Chen  LH, Chen  CH, Lin  SY,  et al.  Aggressive continuous passive motion exercise does not improve knee range of motion after total knee arthroplasty.  J Clin Nurs. 2013;22(3-4):389-394.PubMedGoogle ScholarCrossref
35.
Colwell  CW  Jr, Morris  BA.  The influence of continuous passive motion on the results of total knee arthroplasty.  Clin Orthop Relat Res. 1992;(276):225-228.PubMedGoogle Scholar
36.
Denis  M, Moffet  H, Caron  F, Ouellet  D, Paquet  J, Nolet  L.  Effectiveness of continuous passive motion and conventional physical therapy after total knee arthroplasty: a randomized clinical trial.  Phys Ther. 2006;86(2):174-185.PubMedGoogle Scholar
37.
Harms  M, Engstrom  B.  Continuous passive motion as an adjunct to treatment in the physiotherapy management of the total knee arthroplasty patient.  Physiotherapy. 1991;77(4):301-307. doi:10.1016/S0031-9406(10)61768-3Google ScholarCrossref
38.
Kim  TK, Park  KK, Yoon  SW, Kim  SJ, Chang  CB, Seong  SC.  Clinical value of regular passive ROM exercise by a physical therapist after total knee arthroplasty.  Knee Surg Sports Traumatol Arthrosc. 2009;17(10):1152-1158.PubMedGoogle ScholarCrossref
39.
Lenssen  A, de Bie  RA, Bulstra  SK, van Steyn  MJA.  Continuous passive motion (CPM) in rehabilitation following total knee arthroplasty: a randomised controlled trial.  Phys Ther Rev. 2003;(8):123-129. doi:10.1179/108331903225003019Google Scholar
40.
Lenssen  TA, van Steyn  MJ, Crijns  YH,  et al.  Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.  BMC Musculoskelet Disord. 2008;9:60.PubMedGoogle ScholarCrossref
41.
MacDonald  SJ, Bourne  RB, Rorabeck  CH, McCalden  RW, Kramer  J, Vaz  M.  Prospective randomized clinical trial of continuous passive motion after total knee arthroplasty.  Clin Orthop Relat Res. 2000;(380):30-35.PubMedGoogle Scholar
42.
Maniar  RN, Baviskar  JV, Singhi  T, Rathi  SS.  To use or not to use continuous passive motion post–total knee arthroplasty presenting functional assessment results in early recovery.  J Arthroplasty. 2012;27(2):193-200.e1.PubMedGoogle ScholarCrossref
43.
May  LA, Busse  W, Zayac  D, Whitridge  MR.  Comparison of continuous passive motion (CPM) machines and lower limb mobility boards (LLiMB) in the rehabilitation of patients with total knee arthroplasty.  Can J Rehabil. 1999;12:257-263.Google Scholar
44.
McInnes  J, Larson  MG, Daltroy  LH,  et al.  A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty.  JAMA. 1992;268(11):1423-1428.PubMedGoogle ScholarCrossref
45.
Montgomery  F, Eliasson  M.  Continuous passive motion compared to active physical therapy after knee arthroplasty: similar hospitalization times in a randomized study of 68 patients.  Acta Orthop Scand. 1996;67(1):7-9.PubMedGoogle ScholarCrossref
46.
Pope  RO, Corcoran  S, McCaul  K, Howie  DW.  Continuous passive motion after primary total knee arthroplasty: does it offer any benefits?  J Bone Joint Surg Br. 1997;79(6):914-917.PubMedGoogle ScholarCrossref
47.
Sahin  E, Akalin  E, Bircan  C,  et al.  The effects of continuous passive motion on outcome in total knee arthroplasty.  J Rheumatol Med Rehabil. 2006;17(2):85-90.Google Scholar
48.
Walker  RH, Morris  BA, Angulo  DL, Schneider  J, Colwell  CW  Jr.  Postoperative use of continuous passive motion, transcutaneous electrical nerve stimulation, and continuous cooling pad following total knee arthroplasty.  J Arthroplasty. 1991;6(2):151-156.PubMedGoogle ScholarCrossref
49.
Calatayud  J, Casaña  J, Ezzatvar  Y, Jakobsen  MD, Sundstrup  E, Andersen  LL.  High-intensity preoperative training improves physical and functional recovery in the early post-operative periods after total knee arthroplasty: a randomized controlled trial [published online January 14, 2016].  Knee Surg Sports Traumatol Arthrosc. PubMedGoogle Scholar
50.
Gstoettner  M, Raschner  C, Dirnberger  E, Leimser  H, Krismer  M.  Preoperative proprioceptive training in patients with total knee arthroplasty.  Knee. 2011;18(4):265-270.PubMedGoogle ScholarCrossref
51.
McKay  C, Prapavessis  H, Doherty  T.  The effect of a prehabilitation exercise program on quadriceps strength for patients undergoing total knee arthroplasty: a randomized controlled pilot study.  PM R. 2012;4(9):647-656.PubMedGoogle ScholarCrossref
52.
Albrecht  S, le Blond  R, Köhler  V,  et al.  [Cryotherapy as analgesic technique in direct, postoperative treatment following elective joint replacement]  [in German].  Z Orthop Ihre Grenzgeb. 1997;135(1):45-51.PubMedGoogle ScholarCrossref
53.
Gibbons  CE, Solan  MC, Ricketts  DM, Patterson  M.  Cryotherapy compared with Robert Jones bandage after total knee replacement: a prospective randomized trial.  Int Orthop. 2001;25(4):250-252.PubMedGoogle ScholarCrossref
54.
Ivey  M, Johnston  RV, Uchida  T.  Cryotherapy for postoperative pain relief following knee arthroplasty.  J Arthroplasty. 1994;9(3):285-290.PubMedGoogle ScholarCrossref
55.
Kullenberg  B, Ylipää  S, Söderlund  K, Resch  S.  Postoperative cryotherapy after total knee arthroplasty: a prospective study of 86 patients.  J Arthroplasty. 2006;21(8):1175-1179.PubMedGoogle ScholarCrossref
56.
Levy  AS, Marmar  E.  The role of cold compression dressings in the postoperative treatment of total knee arthroplasty.  Clin Orthop Relat Res. 1993;(297):174-178.PubMedGoogle Scholar
57.
Morsi  E.  Continuous-flow cold therapy after total knee arthroplasty.  J Arthroplasty. 2002;17(6):718-722.PubMedGoogle ScholarCrossref
58.
Radkowski  CA, Pietrobon  R, Vail  TP, Nunley  JA  II, Jain  NB, Easley  ME.  Cryotherapy temperature differences after total knee arthroplasty: a prospective randomized trial.  J Surg Orthop Adv. 2007;16(2):67-72.PubMedGoogle Scholar
59.
Smith  J, Stevens  J, Taylor  M, Tibbey  J.  Bandaging and cold therapy in total knee replacement surgery.  Orthop Nurs. 2002;21(2):61-66.PubMedGoogle ScholarCrossref
60.
Su  EP, Perna  M, Boettner  F,  et al.  A prospective, multi-center, randomised trial to evaluate the efficacy of a cryopneumatic device on total knee arthroplasty recovery.  J Bone Joint Surg Br. 2012;94(11)(suppl A):153-156.PubMedGoogle ScholarCrossref
61.
Thienpont  E.  Does advanced cryotherapy reduce pain and narcotic consumption after knee arthroplasty?  Clin Orthop Relat Res. 2014;472(11):3417-3423.PubMedGoogle ScholarCrossref
62.
Webb  JM, Williams  D, Ivory  JP, Day  S, Williamson  DM.  The use of cold compression dressings after total knee replacement: a randomized controlled trial.  Orthopedics. 1998;21(1):59-61.PubMedGoogle Scholar
63.
Adravanti  P, Nicoletti  S, Setti  S, Ampollini  A, de Girolamo  L.  Effect of pulsed electromagnetic field therapy in patients undergoing total knee arthroplasty: a randomised controlled trial.  Int Orthop. 2014;38(2):397-403.PubMedGoogle ScholarCrossref
64.
Borckardt  JJ, Reeves  ST, Robinson  SM,  et al.  Transcranial direct current stimulation (tDCS) reduces postsurgical opioid consumption in total knee arthroplasty (TKA).  Clin J Pain. 2013;29(11):925-928.PubMedGoogle ScholarCrossref
65.
Moretti  B, Notarnicola  A, Moretti  L,  et al.  I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study.  BMC Musculoskelet Disord. 2012;13(1):88.PubMedGoogle ScholarCrossref
66.
Chen  CC, Yang  CC, Hu  CC, Shih  HN, Chang  YH, Hsieh  PH.  Acupuncture for pain relief after total knee arthroplasty: a randomized controlled trial.  Reg Anesth Pain Med. 2015;40(1):31-36.PubMedGoogle ScholarCrossref
67.
Mikashima  Y, Takagi  T, Tomatsu  T, Horikoshi  M, Ikari  K, Momohara  S.  Efficacy of acupuncture during post-acute phase of rehabilitation after total knee arthroplasty.  J Tradit Chin Med. 2012;32(4):545-548.PubMedGoogle ScholarCrossref
68.
Tsang  RC, Tsang  PL, Ko  CY, Kong  BC, Lee  WY, Yip  HT.  Effects of acupuncture and sham acupuncture in addition to physiotherapy in patients undergoing bilateral total knee arthroplasty: a randomized controlled trial.  Clin Rehabil. 2007;21(8):719-728.PubMedGoogle ScholarCrossref
69.
Tzeng  CY, Chang  SL, Wu  CC,  et al.  Single-blinded, randomised preliminary study evaluating the effects of 2 Hz electroacupuncture for postoperative pain in patients with total knee arthroplasty.  Acupunct Med. 2015;33(4):284-288.PubMedGoogle ScholarCrossref
70.
Bjordal  JM, Johnson  MI, Ljunggreen  AE.  Transcutaneous electrical nerve stimulation (TENS) can reduce postoperative analgesic consumption: a meta-analysis with assessment of optimal treatment parameters for postoperative pain.  Eur J Pain. 2003;7(2):181-188.PubMedGoogle ScholarCrossref
71.
Joshi  RN, White  PB, Murray-Weir  M, Alexiades  MM, Sculco  TP, Ranawat  AS.  Prospective randomized trial of the efficacy of continuous passive motion post total knee arthroplasty: experience of the Hospital for Special Surgery.  J Arthroplasty. 2015;30(12):2364-2369.PubMedGoogle ScholarCrossref
72.
Cabilan  CJ, Hines  S, Munday  J.  The effectiveness of prehabilitation or preoperative exercise for surgical patients: a systematic review.  JBI Database System Rev Implement Rep. 2015;13(1):146-187.PubMedGoogle ScholarCrossref
73.
Hoogeboom  TJ, Oosting  E, Vriezekolk  JE,  et al.  Therapeutic validity and effectiveness of preoperative exercise on functional recovery after joint replacement: a systematic review and meta-analysis.  PLoS One. 2012;7(5):e38031.PubMedGoogle ScholarCrossref
74.
Santa Mina  D, Clarke  H, Ritvo  P,  et al.  Effect of total-body prehabilitation on postoperative outcomes: a systematic review and meta-analysis.  Physiotherapy. 2014;100(3):196-207.PubMedGoogle ScholarCrossref
×