Evidence Review Process - ESRA
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Total Knee Arthroplasty 2020

Evidence Review Process

An explanation of PROSPECT methodology and Working Group processes can be found at the following link: https://esraeurope.org/prospect-methodology

For the TKA review, the Subgroup members were:

  • Patricia M. Lavand’homme1
  • Henrik Kehlet2
  • Narinder Rawal3
  • Girish P. Joshi4
  1. Department of Anaesthesiology and Perioperative Pain Service, Cliniques Universitaires St Luc, University Catholic of Louvain (UCL), Brussels, Belgium.
  2. Section of Surgical Pathophysiology 7621, Rigshospitalet, Copenhagen, Denmark.
  3. Department of Anaesthesiology, Orebro University, Orebro, Sweden.
  4. Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas, United States.

TKA literature strategy

  • Given the large number of RCTs evaluating pain management for TKA, the PROSPECT Working Group used the process of Adolopment to critically assess published systematic reviews and meta-analyses evaluating individual analgesic interventions for TKA, rather than repeat much of the work of previous reviews. This process combines adoption, adaptation, and de novo development of guidelines recommendations (Tugwell, Knottnerus 2017).

Literature search

  • The EMBASE, MEDLINE, PubMed and Cochrane Databases were searched between January 2014 and December 2020 to identify relevant systematic reviews and meta-analyses (however, RCTs in the selected systematic reviews and meta-analyses were published since database inception).

Search terms:

  • ‘‘Knee replacement’’ OR ‘‘knee arthroplasty’’ AND ‘‘postoperative pain’’ AND ‘‘meta-analysis’’ OR ‘‘systematic review’’.

Inclusion criteria:

  • Published systematic reviews and meta-analyses that assessed systemic or regional analgesic interventions for pain management in patients undergoing unilateral, primary TKA. The included systematic reviews and meta-analyses were performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) recommendations.
  • From these publications, individual RCTs were identified that met the PROSPECT criteria; all included RCTs reported on pain intensity according to validated pain scales (e.g. VAS, NRS).


  • Anaesthetic techniques, surgical techniques, and nonpharmacological interventions were not reviewed.

Included studies:

  • From 151 systematic reviews that were analysed, 106 RCTs were identified that met PROSPECT criteria.

Risk of bias assessments

Risk of bias of individual RCTs was not assessed as it had already been performed by the authors of the systematic reviews and meta-analyses.

  • Data extraction and data analysis for TKA adhered to the PROSPECT methodology (Joshi 2019, https://esraeurope.org/prospect-methodology).
  • Primary outcome: the degree of pain as measured by pain scores. Clinically relevant differences in pain scores were at least 1/10 cm or 10/100 mm on the VAS or 1/10 points on VAS/NRS.
  • Secondary outcomes included: reduction of opioid-related side effects, passive knee mobilisation and active rehabilitation, where reported.
  • Recommendations were made according to PROSPECT methodology (Joshi 2019, https://esraeurope.org/prospect-methodology).
  • To formulate the PROSPECT recommendations, each analgesic technique was critically evaluated in terms of its clinically relevant effects on pain scores, added benefit when used together with non-opioid analgesics, invasiveness, side effects, and current clinical relevance.
  • Particular attention was paid to the added benefits of co-analgesics (paracetamol and NSAIDs or COX-2-specific inhibitors) in addition to LIA, because of their well-documented analgesic effects, and being simple, inexpensive and safe (NICE guidelines. NG157, 2020).
  • Evidence of the safety of analgesic interventions was based on RCTs and cohort studies from various types of procedure, not only TKA.
  • The PROSPECT Working Group reviewed the proposed recommendations, together with the details of the individual RCTs, and provided comments. A modified Delphi approach was used to achieve a consensus. The lead authors drafted the final document that was ultimately approved by the Working Group.

The evidence included in this review has limitations, including:

  • Studies show heterogeneity with regards to anaesthetic and analgesic techniques as well as variability in outcomes assessed.
  • Many studies did not report administration of basic analgesics (NSAIDs or COX-2-specific inhibitors combined with paracetamol), which precludes an objective evaluation of the benefits of the analgesic intervention studied (Karlsen 2018).
  • Many studies lacked assessment of the effects of analgesic interventions on functional outcomes, hospital length of stay, persistent postoperative pain, and patient-related outcomes.
  • None of the included studies reported use of enhanced recovery protocols, even though these are increasingly implemented (Kehlet 2020).
  • No high-quality studies assess the relative importance of the different analgesic techniques to facilitate an outpatient TKA facility.
  • Evidence on the use of peripheral nerve blocks in TKA is not based on studies with a short, 1–2 days, inpatient stay or an outpatient TKA facility, thereby limiting the conclusions for current practice in many places.
  • Due to the use of a modified methodology to search the literature for systematic reviews and meta-analyses, rather than individual RCTs, it is possible that RCTs evaluating newer regional analgesia techniques for TKA were not included, such as iPACK, cryoanalgesia, genicular nerve block, saphenous nerve block, and methocarbamol. However, these interventions could not have been recommended due to limited procedure-specific evidence.

It is possible that analgesic interventions that were not recommended because of limited analgesic efficacy and/or concerns of adverse effects may be appropriate in patients at high risk of postoperative pain or when the currently recommended interventions are not possible. The current recommendations do not address:

  • Pain management in patients undergoing re-operation or associated secondary surgical procedures.
  • Specific groups of patients with factors that adversely affect postoperative pain (Pedersen 2020; DeMik 2020; Kehlet, Memtsoudis 2020), e.g. patients with severe acute postoperative pain despite standardised postoperative analgesia, such as those with pre-operative chronic pain conditions, those taking pre-operative opioids, and patients with psychiatric disorders.