Effect of steroid in local infiltrative analgesia in one-stage bilateral total knee arthroplasty. A paired-randomized controlled study

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Effect of steroid in local infiltrative analgesia in one-stage bilateral total knee arthroplasty. A paired-randomized controlled study Vincent Chan 1, Chan PK 1, Chiu KY 1, Yan CH 1, FU CH 1, Chan CW 2 Division of Joint Replacement Surgery 1 Department of Orthopaedics and Traumatology 1 Department of Anaesthesiology 2 Queen Mary Hospital

Total Knee Arthroplasty Most successful for advanced OA knees Severe post-operative pain unresolved Multimodal, opioid sparing Options: Peripheral nerve blocks Epidural infusion Delay mobilization Patient-controlled analgesia Local infiltrative analgesia (LIA) Andersen. Anaesthesia 2009 Banerjee. Orthopedic 2013 Kerr and Kohan Acta Orthpaedica 2008

LIA Intra-op peri-articular injection of: Local anesthetic, adrenaline and NSAID Minimal side effects Proven effectiveness in multiple RCTs and meta-analysis Limitations Short duration Unclear role of individual components Andersen and Kehlet. Br J of Anaes 2014 Xu. The Knee 2014 Ng. JOA 2012 Kerr and Kohan. Acta Orthp 2008

Aim Study Aim and Hypothesis Evaluate the role of steroid in LIA Hypothesis Potent and long acting anti-inflammatory enhances LIA Local anesthetic Adrenaline NSAID STEROID Local anesthetic Adrenaline NSAID

LIA without steroid (n=26) Deep 75mg Ropivacaine 7.5mg Ketorolac 0.5mg Adrenaline Subcutaneous 75mg Ropivacaine 7.5mg Ketorolac Randomization Standardized LIA injections Avoid steroid in subcutaneous tissue and tendon (n=26) LIA with steroid (n=26) Deep 75mg Ropivacaine 7.5mg Ketorolac 0.5mg Adrenaline 40mg Triamcinolone Subcutaneous 75mg Ropivacaine 7.5mg Ketorolac Follow-up at 6 weeks and 3 months

Baseline characteristics LIA without steroid (n = 26) LIA with steroid (n = 26) P-value VAS at rest 1.4 ± 2.1 1.7 ± 2.3 0.30 VAS during activity 6.5 ± 2.0 6.4 ± 2.3 0.80 Passive ROM 94 ± 18 94 ± 19 0.80 Clinical, Radiological and Functional Active ROM 93 ± 17 92 ± 18 0.43 parameters are comparable Pre-op MTFA 13.6 ± 6.2 13.1 ± 5.8 0.79 Post-op MTFA 3.4 ± 3.7 3 ± 3.5 0.69 OT time (min) 73.2 ± 26 77 ± 30 0.24 Knee Society Score 41 ± 14 41 ± 13 0.62

VAS score at rest and during activity 8 7 6 5 4 Rest without steroid Rest with steroid Activity without steroid Activity with steroid 3 2 1 0 2hr 6hr 12hr D1 D2 D3 D4 D5 D6 D7 6wk 3mo denote p-value <0.05

Degrees 105 Active and passive ROM 100 95 90 85 80 75 70 65 60 Passive without steroid Passive with steroid Active without steroid Active with steroid D1 D2 D3 D4 D5 D6 D7 6wk 3mo denote p-value <0.05

Post-operative parameters LIA without steroid (n = 26) LIA with steroid (n = 26) P-value Time to achieve SLR 1.9 ± 1.7 1.2 ± 0.7 0.0067 Knee Society Score 83.1 ± 10 82.6 ± 11 0.53 At 6 weeks Knee Society Score 89.8 ± 5.6 89.1 ± 5.6 0.80 At 3 months Wound 0 0 1.0 complications Infections 0 0 1.0

DISCUSSION

Limitation of current evidence 7 RCTs on LIA with steroid Methodological limitations Pre-op analgesics not controlled Short outcome measurements Variable controls (NSAID/ adrenaline) Mental health, social status not mentioned Author Year Christensen 2009 Seah 2011 Yue 2013 Chia 2013 Ikeuchi 2014 Kwon 2014 Hoshino 2015

First within subject study to investigate role of components in LIA Pain most subjective Control confounders: Pain perception Peri-op analgesia Psychological state Social-economic backgrounds Increase statistical power Paired t-test, Wilcoxon test Reduce variance Increase power (with same no. of subjects)

Conclusion LIA with steroid provides better pain relief and early rehabilitation outcomes after TKR Local anesthetic Adrenaline NSAID STEROID

Effect of steroid in local infiltrative analgesia in one-stage bilateral total knee arthroplasty. A paired-randomized controlled study Vincent Chan 1, Chan PK 1, Chiu KY 1, Yan CH 1, FU CH 1, Chan CW 2 Division of Joint Replacement Surgery 1 Department of Orthopaedics and Traumatology 1 Department of Anaesthesiology 2 Queen Mary Hospital

Statistics Power analysis (alpha 0.5, power 0.8) 25 patients to detect difference in 2 VAS (minimal clinical important difference) Paired t-test for parametric variables Wilcoxon test for non-parameteric variables Fisher s exact test for categorical variables GraphPad software, San Diego, CA, USA Katz. J or Ortho Surg and Res 2015 Tubach. Ann Rheum Dis 2005 Farrar. Pain 2001

How does LIA with steroid work? Corticosteroid Nuclear steroid receptors Surgical trauma and local inflammation Phospholipase / Arachidonic acid/ COX-2 NSAID Local anesthetic Inflammatory mediators (ie.prostagladins) Peripheral nociceptors PNS/CNS Sensitization Robbin and Cotran s. Path Basis of Disease 8 th Ed. 2010

Clinical implication Readiness to discharge criteria Stable medical and wound condition Good pain control (VAS rest <3 ; activity < 5) Physical (active flexion 90deg) Functional (self-care, independent walking) Within subject comparison on POD 3 Both knees pass Both knees fail No steroid knee passed only Steroid knee passed only 9 (29%) 8 (26%) 0 (0%) 14 (45%) Kehlet. Acta Orthpaedica 2011 Ng. JOA 2012 Chan. Arthritis Care and Res 2014 Egmond. Acta Orthopaedica 2015

Sensitization reduction Less rest pain at 6 weeks Beyond action of triamcinolone (~14days) Acute pain can leads to chronic pain via sensitization Steroid blocks origin of inflammation and pain Reduces sensitization prolong effect? Carr. Lancet 1999 Samad. Nature 2001 Stephens. Am Fam Phys 2008 Yue. Chin Med Jounral 2013

Minimal clinical important difference (MCID) Smallest change in measured outcome perceived as beneficial (or detrimental) by the patient 2pt changes in VAS (0-10) is clinically important in OA knees Katz. J or Ortho Surg and Res 2015 Tubach. Ann Rheum Dis 2005 Farrar. Pain 2001

7 RCT (345 LIA with steroid TKR) No differences in infection and wound complications No patella tendon rupture Still underpowered 3500 TKRs to detect 50% differences in infection rate Zhao. J or Ortho Surg and Res 2015 Hoshino. BJJ 2015