Total Knee Arthroplasty 2020

TKA-specific evidence

Data table: Paracetamol for pain management after TKA

Study details:

• 6 meta-analyses were identified that assessed the analgesic effect of oral and IV paracetamol for patients undergoing TKA, THA or total joint arthroplasty (Guo 2018; Liang 2017; Shi 2018; Sun 2018; Yang 2017; Fillingham 2020). These included 22 studies, of which two RCTs in TKA met PROSPECT inclusion criteria (O’Neal 2017; Murata-Ooiwa 2017).

Arguments for…

• One of two RCTs showed a benefit of paracetamol vs placebo for reducing pain scores (O’Neal 2017; Murata-Ooiwa 2017). No side effects related to treatment were reported.

PROSPECT Recommendations

• Paracetamol and NSAIDs or COX-2-specific inhibitors are recommended, administered either preoperatively or intra-operatively, for management of postoperative pain after TKA.
• The recommendation for paracetamol is based on evidence in TKA from two RCTs of paracetamol (Murata-Ooiwa 2017; O’Neal 2017).
• A meta-analysis concluded that although paracetamol alone has limited analgesic and opioid-sparing efficacy, moderate evidence supports its use for peri-operative pain management after TKA (Fillingham 2020). It is a low-cost and low-risk option and it demonstrates an interesting opioid-sparing effect when combined with NSAIDs (Martinez 2017; Ong 2010).

TKA-specific evidence

Data table: NSAIDs/COX-2-specific inhibitors for pain management after TKA

Study details:

• Two meta-analyses assessed the efficacy and safety of NSAIDs or COX-2-specific inhibitors for patients undergoing TKA (Du 2018; Fillingham 2020). From these, six RCTs evaluating peri-operative COX-2-specific inhibitors were included in the PROSPECT review (Zhu 2014; Essex 2018; Gong 2013; Munteanu 2016; Reynolds 2003; Meunier 2007).

Arguments for…

• Six RCTs showed reduced postoperative pain scores at rest and during mobilisation, and reduced opioid requirements, with use of COX-2-specific inhibitors (Zhu 2014; Essex 2018; Gong 2013; Munteanu 2016; Reynolds 2003; Meunier 2007).
• The benefits of COX-2-specific inhibitors were observed even with concomitant administration of paracetamol or LIA.

Arguments against…

• Results showed no decrease in opioid-related adverse effects like PONV with use of COX-2-specific inhibitors (Zhu 2014; Essex 2018; Gong 2013; Munteanu 2016; Reynolds 2003).

PROSPECT Recommendations

• Paracetamol and NSAIDs or COX-2-specific inhibitors are recommended, administered either preoperatively or intra-operatively, for management of postoperative pain after TKA.
• Recommendations for NSAIDs or COX-2-specific inhibitors are based on evidence in TKA from six studies of COX-2-specific inhibitors, showing analgesic and opioid-sparing effects (Zhu 2014; Essex 2018; Gong 2013; Munteanu 2016; Reynolds 2003; Meunier 2007).
• This is in agreement with the strong recommendation for NSAIDs and COX-2-specific inhibitors in a meta-analysis by Fillingham 2020.
• COX-2-specific inhibitors possess similar analgesic efficacy to NSAIDs but with no effects on platelet function, and thus, could be administered preoperatively.
• A meta-analysis found that NSAIDs are unlikely to be the cause of postoperative bleeding complications (Bongiovanni 2021).
• No safety concerns were reported with NSAIDs and COX-2-specific inhibitors but prescribers need to remain vigilant as the typical older TKA population may be at a higher risk of adverse effects (Fillingham 2020).

TKA-specific evidence

Data table: Glucocorticoids for pain management after TKA

Study details:

• From 12 systematic reviews and meta-analyses assessing the use of glucocorticoid for patients undergoing TKA/THA (Kehlet 2020), six RCTs in TKA met the PROSPECT criteria and were included (Lunn 2011; Koh 2013; Xu B 2018; Xu H 2018; Dissanayake 2018; Li 2019).
  • All included some combination of paracetamol, NSAIDs/COX-2-specific inhibitors and LIA.

Arguments for…

• Three RCTs assessed a single pre-operative dose of glucocorticoid (dose between 10 to 25 mg of dexamethasone equivalents) and showed a reduction in pain, postoperative analgesic consumption and PONV, with no safety issues (Lunn 2011; Koh 2013; Xu H 2018).
  • The safety of a single pre-operative glucocorticoid dose is supported by a large before and after implementation study (Jørgensen 2017) and a systematic review (Feeley 2021).
• Four RCTs assessed repeat dosing of glucocorticoids and showed a significant reduction in postoperative pain up to 48 h, together with reduction in postoperative opioid requirements and PONV (Xu B 2018; Xu H 2018; Dissanayake 2018; Li 2019).

Arguments against…

• No dose-finding studies were identified.
• No safety studies are available for repeat-dosing regimens. Within the included RCTs, no safety issues were identified with repeat dosing but the total number of glucocorticoid-treated patients was small (n=150) (Xu B 2018; Xu H 2018; Dissanayake 2018; Li 2019).
• Several RCTs on local administration of glucocorticoids together with LIA are available (Kehlet 2020) but interpretation is hindered by the lack of a systemic dose for control.

PROSPECT Recommendations

• Dexamethasone (≥10 mg, IV) is recommended, administered intra-operatively, for management of postoperative pain after TKA.
• The recommendation is based on three RCTs assessing a single preoperative dose of glucocorticoid (from 10 to 25 mg of dexamethasone equivalents) (Koh 2013; Xu H 2018; Lunn 2011). These showed a reduction in pain, postoperative analgesic consumption and PONV, and no safety issues, even with concomitant use of paracetamol, NSAIDs/COX-2-specific inhibitors and LIA.
• A single, intra-operative IV dexamethasone dose is simple, safe and effective with concomitant use of basic analgesics and LIA (Kehlet 2020). The optimal dose remains undetermined as the dose used in the different RCTs varied.
• The safety of repeated doses of glucocorticoids to improve postoperative recovery remains questionable.
• Although side effects of wound healing and infections are of potential concern, these have so far not been demonstrated, although more data are required in diabetic patients (Jørgensen 2017; Feeley 2021).

TKA-specific evidence

Data table: Systemic α2-adrenergic agonists for pain management after TKA

Study details:

• From one meta-analysis evaluating the efficacy and safety of IV dexmedetomidine in patients undergoing TKA and THA (Yang 2020), two RCTs focused on TKA met the PROSPECT criteria (Chan 2016; Shin 2019):
  • A dexmedetomidine bolus (0.5–1.0 µg/kg) then continuous infusion (0.1–0.5 µg/kg/h until the end of surgery) was compared with placebo (Chan 2016) or propofol sedation (Shin 2019) in patients undergoing TKA under spinal anaesthesia; postoperative opioid-sparing effect was the primary endpoint in both studies.
  • Both studies used basic analgesia (paracetamol and NSAIDs); Shin 2019 also used femoral nerve block, LIA, pregabalin and dexamethasone.

Arguments for…

• Dexmedetomidine significantly reduced postoperative morphine, itching and PONV vs placebo (Chan 2016), but there was no significant difference in postoperative pain scores.
• Dexmedetomidine significantly reduced postoperative fentanyl consumption vs propofol sedation (Shin 2019), but there was no significant difference in postoperative anti-emetic use.

Arguments against…

• In the procedure-specific studies, dexmedetomidine was used for sedation during spinal anaesthesia (Chan 2016; Shin 2019).
• There are concerns of adverse effects, such as bradycardia and hypotension, with use of dexmedetomidine.

PROSPECT Recommendations

• Dexmedetomidine is not recommended for management of postoperative pain after TKA due to inconsistent procedure-specific evidence.

TKA-specific evidence

Data tables:
Gabapentin for pain management after TKA
Pregabalin for pain management after TKA

Study details:

• Six meta-analyses evaluated gabapentinoids for analgesia in patients undergoing TKA (Joshi, Kehlet 2021).
• Four systematic reviews assessed gabapentin administration (Kang 2020; Han 2016; Zhai 2016; Hamilton 2016), including eight RCTs, of which four were included in the PROSPECT review (Clarke 2009; Clarke 2014; Paul 2013; Lunn 2015).
  • The postoperative analgesic regimen included NSAIDs or COX-2-specific inhibitors ± paracetamol in only three RCTs; a perineural catheter was used in one RCT.
• Four systematic reviews/meta-analyses assessed pregabalin administration (Hamilton 2016; Dong 2016; Han 2017; Li 2017), including eight RCTs, of which six were included in the PROSPECT review (Buvanendran 2010; Jain 2012; Lee 2015; Singla 2015; YaDeau 2015; Yik 2019).
  • All included RCTs used regional anaesthesia (combined spinal epidural or spinal alone), and most used regional analgesia; one administered IV PCA.

Arguments against…

• Procedure-specific evidence shows a lack of clinically-relevant analgesic benefit and minimal opioid-sparing effects when gabapentinoids are used together with paracetamol, NSAID/COX-2-specific inhibitors and LIA (Clarke 2009; Clarke 2014; Paul 2013; Lunn 2015; Buvanendran 2010; Jain 2012; Lee 2015; Singla 2015; YaDeau 2015; Yik 2019).
• The studies showed a significant variation in the dose, timing of pre-operative administration and duration of postoperative administration of gabapentin and pregabalin.

PROSPECT Recommendations

• Gabapentinoids are not recommended due to minimal analgesic and opioid-sparing effects and concerns of potential adverse effects, particularly when combined with postoperative opioids, which are typically high for TKA.

TKA-specific evidence

Data table: Systemic ketamine for pain management after TKA

Study details:

• Three meta-analyses assessed analgesic effects of peri-operative systemic ketamine after TKA (Li 2019) or after TKA/THA (Wang 2020; Xu 2019). From these, five RCTs were identified that examined IV low doses of ketamine after TKA vs placebo (Adam 2005; Aveline 2009; Perrin 2009; Cengiz 2014; Tan 2019). Aveline 2009 also included a nefopam group.
  • Ketamine was administered as a bolus dose (0.5 mg/kg) followed by a continuous infusion either until the end of surgery (4 to 6 µg/kg/min; Perrin 2009; Cengiz 2014; Tan 2019) or over 48 h after surgery (1.5 to 3 µg/kg/min; Adam 2005; Aveline 2009).

Arguments for…

• In two RCTs, ketamine administration was associated with significant analgesic effect vs placebo at rest and during mobilisation, independent of the duration of administration (Aveline 2009; Cengiz 2014). However, PCA morphine alone was available for postoperative analgesia and non-opioid analgesics were not administered.
• Systemic ketamine was associated with significant opioid-sparing in four of five studies (Aveline 2009; Cengiz 2014; Adam 2005; Perrin 2009).
• Two RCTs found that ketamine was associated with faster passive rehabilitation (Aveline 2009; Adam 2005).
• In one study, ketamine was more effective than nefopam in reducing postoperative pain (Aveline 2009).

Arguments against…

• When a basic analgesic regimen (NSAID, paracetamol and/or LIA) (Tan 2019) or continuous FNB (Adam 2005) was used, systemic ketamine did not significantly reduce postoperative pain intensity.
• Systemic ketamine did not affect the incidence of opioid side effects (PONV), despite the opioid-sparing effect (Aveline 2009; Cengiz 2014; Adam 2005; Perrin 2009).
• Four RCTs questioned the long-term benefits of peri-operative ketamine without clear evidence regarding chronic pain development (Adam 2005; Aveline 2009; Perrin 2009; Tan 2019).

PROSPECT Recommendations

• Ketamine is not recommended for management of postoperative pain after TKA due to conflicting procedure-specific evidence.

TKA-specific evidence

Data table: Adductor canal block (ACB) for pain management after TKA

Study details:

• 26 systematic reviews and meta-analyses reported on ACB in TKA:
  • ACB vs FNB (n=8) (Dong 2016; Gao 2017; Kuang 2017; Kuang 2016; Li 2016; Wang 2017; Zhang 2019; Zhao 2016)
  • ACB vs LIA (n=10) (Li 2018; Lv 2020; Zhao 2019; Zuo 2019; Sardana 2019; Hussain 2021; Mingdeng 2022; Fan 2017; Fan 2015; Zhang 2019)
  • ACB technique (n=7) (Yu 2020; Sun 2020; Wang 2019; Zhang 2019; Schnabel 2019)
• Five RCTs compared ACB vs saline ACB (bolus or repeated boluses or continuous infusion) (Jenstrup 2012; Jaeger 2012; Grevstad 2014; Hanson 2014; Zhang 2014).
  • Jaeger 2012 and Grevstad 2014 evaluated rescue (postoperative) ACB in patients with severe postoperative pain either at 6 h or on postoperative day 2.
  • A multimodal analgesic protocol was used in all studies.
• Four RCTs compared single shot ACB with single shot FNB (Kim 2014; Grevstad 2015; Memtsoudis 2015; Macrinici 2017), while eight RCTs compared continuous ACB with continuous FNB (Li 2016).
• Seven RCTs compared single shot ACB with continuous ACB (Shah 2015; Turner 2018; Lee 2018; Elkassabany 2019; Zhang Y 2018; Lyngeraa 2019; Canbek 2019).
  • The majority of studies used a multimodal analgesic protocol.
• Eight RCTs compared ACB with LIA (Li 2017; Sawhney 2016; Grosso 2018; Zhou 2018; Kampitak 2018; Tong 2018; Nader 2016; Cicekci 2019).
  • The majority of studies used multimodal analgesia with paracetamol, COX-2-specific inhibitor, gabapentinoid and systemic opioid.
  • There was significant variability in the LIA volume (40 and 100 ml, five of eight RCTs) or solution (three of eight RCTs).
• Five RCTs compared a combination of ACB and LIA vs ACB alone (Sawhney 2016; Grosso 2018; Kampitak 2018; Zhou 2018; Goytizolo 2019).
  • All studies included a multimodal analgesic regimen.
• Five RCTs compared a combination of ACB and LIA vs LIA alone (Sawhney 2016; Kampitak 2018; Goytizolo 2019; Andersen 2013; Gudmundsdottir 2017).
  • All the studies used a multimodal analgesic regimen, except one (Andersen 2013) where patients received only paracetamol and morphine but no NSAIDs.

Arguments for…

• ACB significantly reduced pain associated with knee flexion and mobilisation vs saline ACB (Jenstrup 2012; Jaeger 2012; Grevstad 2014; Hanson 2014; Zhang 2014).
• In patients with severe postoperative pain, ACB provided pain relief at rest and during knee flexion with a duration of up to 6 h (Jaeger 2012; Grevstad 2014).
• Single shot ACB and single shot FNB were associated with similar analgesic effects and opioid use (Kim 2014; Grevstad 2015; Memtsoudis 2015; Macrinici 2017), but SSACB allowed superior knee function and mobilisation by sparing quadriceps muscle function.
• Continuous ACB and continuous FNB were also similar in terms of postoperative analgesia and opioid use, but continuous ACB allowed better preservation of knee function than FNB by sparing the quadriceps (Li 2016).
• In four RCTs, ACB had greater analgesic efficacy than LIA, particularly regarding dynamic pain (Sawhney 2016; Kampitak 2018; Nader 2016; Cicekci 2019); in three RCTs, ACB was not inferior to LIA (Grosso 2018; Zhou 2018; Tong 2018).
• ACB alone was equivalent (three of five RCTs) or inferior (two of five RCTs) to a combination of ACB and LIA in terms of analgesia and opioid consumption (Sawhney 2016; Grosso 2018; Kampitak 2018; Zhou 2018; Goytizolo 2019).
• The combination of ACB and LIA was superior to LIA for pain control only during the first 24 h (Sawhney 2016; Kampitak 2018; Goytizolo 2019; Andersen 2013; Gudmundsdottir 2017).

Arguments against…

• A decrease in postoperative opioid use was inconsistent, with no impact on PONV, when ACB was compared with saline ACB (Jenstrup 2012; Jaeger 2012; Grevstad 2014; Hanson 2014; Zhang 2014).
• There was no significant benefit of continuous ACB compared with single shot ACB in terms of analgesia and use of rescue opioids in six of seven RCTs (Shah 2015; Turner 2018; Lee 2018; Elkassabany 2019; Zhang Y 2018; Lyngeraa 2019; Canbek 2019). One study questioned the benefit of 48-h ACB infusion over 24-h or single shot ACB (Elkassabany 2019).
• In one study, no important differences were found between ACB bolus (20 ml bupivacaine 0.25% plus clonidine, dexamethasone and buprenorphine) and continuous infusion using local anaesthetic alone (Turner 2018).
• Postoperative opioid consumption was similar between ACB and LIA in some studies, whereas in others opioid-sparing was greater in one group but without reduction of opioid-related adverse effects (Li 2017; Sawhney 2016; Grosso 2018; Zhou 2018; Kampitak 2018; Tong 2018; Nader 2016; Cicekci 2019).
• The combination of ACB and LIA was not superior to LIA alone regarding opioid-sparing effect (Sawhney 2016; Kampitak 2018; Goytizolo 2019; Andersen 2013; Gudmundsdottir 2017).

PROSPECT Recommendations

• Single shot adductor canal block (ACB) administered pre-operatively and peri-articular local infiltration analgesia (LIA) administered intra-operatively are recommended. The combination of these two techniques is preferred.
• ACB demonstrates similar analgesic efficacy to FNB but seems to better preserve quadriceps function (Kim 2014; Grevstad 2015; Memtsoudis 2015; Macrinici 2017).
• As ACB have analgesic effects limited to the anteromedial aspect of the knee, leaving the lateral and posterior compartments untargeted, the use of complementary blocks, such as LIA is recommended.

TKA-specific evidence

Study details:

• Meta-analyses assessing the analgesic efficacy of LIA report considerable heterogeneity including variability in types and doses of local anaesthetics used, volumes of injectate, types of analgesic adjuvant (clonidine, ketorolac, morphine), and injection sites.
• Five meta-analyses compared LIA vs no injection or placebo (Andersen, Kehlet 2014; Xu 2014; Seangleulur 2016; Fang 2015; Zhang, Shen 2018).
• Four meta-analyses examined placement of intra-articular catheter and subcutaneous catheter (Andersen, Kehlet 2014; Seangleulur 2016; Zhang, Shen 2018; Sun 2015).
• Meta-analyses compared LIA with various peripheral nerve blocks (Terkawi 2017; Hu 2016; Dong 2016; Gao 2017; Kuang 2016; Li D 2016; Wang 2017; Zhao 2016; Mei 2015; Yun 2015; Albrecht 2016; Elkassabany 2016; Abdallah 2016; Grape 2016; Li J 2016; Ma 2017; Fan 2015; Hussain 2016; Jiang 2016; Li, Ma 2016; Paul 2010; Wang 2015; Ma 2020).
• Six meta-analyses and a Cochrane review evaluated the potential benefits of liposomal bupivacaine (Elkassabany 2016; Wu 2016; Kuang 2017; Singh 2017; Wang 2017; Liu 2019; Sun 2019; Hamilton 2017).

Arguments for…

• Overall, the included RCTs showed improved pain relief and reduced opioid requirements with LIA, as well as earlier functional recovery, range of motion, time to straight leg raise and 90° knee flexion but influence on hospital length of stay was inconsistent (Andersen, Kehlet 2014; Xu 2014; Seangleulur 2016; Fang 2015; Zhang, Shen 2018).
  • A systematic review found that peri-articular, but not intra-articular injection, reduced pain at rest at 24 and 48 h and increased range of motion vs no injection or placebo (n=7 RCTs) (Seangleulur 2016).
• The included RCTs showed that catheter LIA technique was associated with reduced pain and opioid requirements up to 72 h postoperatively.
  • Placement of intra-articular catheter (n=10 RCTs) and subcutaneously (n=1 RCT) was associated with reduced pain and opioid requirements up to 72 h postoperatively (Andersen, Kehlet 2014; Seangleulur 2016).
  • Similar conclusions were drawn by Zhang, Shen 2018 (n=7 RCTs) and Sun 2015 (n=10 RCTs).
• RCTs comparing LIA with ACB are reported in the ACB section.
• Meta-analyses comparing LIA with FNB showed mixed results (Terkawi 2017; Mei 2015; Yun 2015; Albrecht 2016; Wang 2015; Hu 2016).
• One meta-analysis found that the use of continuous peripheral nerve blocks (FNB or ACB) does not provide superior analgesic benefit over single shot LIA (Ma 2020).
• Cost-effectiveness of LIA has been supported by the NICE guidelines (NICE guideline [NG157] 2020).

Arguments against…

• Deep knee infection was reported in 3 of 735 patients receiving a catheter in one meta-analysis (Seangleulur 2016). Similar conclusions were drawn by Sun 2015 (n=10 RCTs).
• The role of liposomal bupivacaine in LIA for TKA remains unclear because of conflicting evidence from six meta-analyses and a Cochrane review (Elkassabany 2016; Wu 2016; Kuang 2017; Singh 2017; Wang 2017; Liu 2019; Sun 2019; Hamilton 2017).

PROSPECT Recommendations

• Single shot adductor canal block (ACB) administered pre-operatively and peri-articular local infiltration analgesia (LIA) administered intra-operatively are recommended. The combination of these two techniques is preferred.
• LIA is an effective, simple and minimally-invasive analgesic technique, which should be considered as ‘basic’ analgesia in combination with paracetamol and NSAIDs/COX-2-specific inhibitors.
• Overall, multiple meta-analyses demonstrated improved pain relief, reduced opioid requirements and earlier functional recovery with LIA compared with no injection or placebo (Andersen 2014; Xu 2014; Seangleulur 2016; Fang 2015; Zhang Y 2018).
• LIA generally includes infiltration of different knee compartments with a cocktail consisting of local anaesthetic (typically, bupivacaine or ropivacaine) and one or more other drugs. However, the added benefit of drugs such as epinephrine or ketorolac is questionable.
• The optimal site and volume for peri-articular administration of drugs remains unclear because of heterogeneity between the studies.
• The NICE expert group reviewed evidence for best anaesthesia and analgesia techniques for knee replacement including costs involved with these techniques, and recommended LIA and peripheral nerve blocks (NICE guideline [NG157] 2020).
• Continuous LIA or continuous intra-articular local anaesthetic infusion are not recommended because of inconsistent benefits and concerns of potential infection.

TKA-specific evidence

Data table: Intrathecal morphine for pain management after TKA

Study details:

• A total of 12 RCTs were identified from systematic reviews and meta-analyses that compared intrathecal morphine with placebo (Cole 2000; Tan 2001; Park 2009; Lauretti 2013; Kunopart 2014; Olive 2015; Sundarathiti 2016; Barrington 2017; Biswas 2018; Kaczocha 2018; Miyamoto 2018; Schumer 2019).
• Two meta-analyses compared intrathecal morphine with FNB (Tang 2017; Li 2016), from which four RCTs were included (Sites 2004; Frassanito 2010; Tarkkila 1998; Olive 2015).
• One meta-analysis compared intrathecal morphine with LIA (Qi 2020), from which four RCTs were included (Essving 2011; Tammachote 2013; Zhang W 2018; McCarthy 2019).

Arguments for…

• A majority of included RCTs showed that intrathecal morphine provided better analgesia than placebo (Cole 2000; Tan 2001; Park 2009; Lauretti 2013; Kunopart 2014; Olive 2015; Sundarathiti 2016; Barrington 2017; Biswas 2018; Kaczocha 2018; Miyamoto 2018; Schumer 2019).

Arguments against…

• When intrathecal morphine was compared with single shot FNB (Sites 2004; Frassanito 2010) there was no significant difference in postoperative pain at rest or during mobilisation and no postoperative opioid-sparing effect.
• The comparison with continuous FNB found no overall benefit of intrathecal morphine (Tarkkila 1998; Olive 2015); although in one study, intrathecal morphine was associated with less postoperative opioid consumption in the immediate postoperative period (6 to 12 h), the consumption was increased at 18 to 24 h (Olive 2015).
• Intrathecal morphine was associated with increased incidence of pruritus and decreased patient satisfaction vs FNB (Sites 2004; Frassanito 2010; Tarkkila 1998; Olive 2015).
• Four RCTs showed no differences in postoperative analgesia and opioid-sparing with intrathecal morphine (100 to 300 µg) vs LIA (Essving 2011; Tammachote 2013; Zhang W 2018; McCarthy 2019).
• Two RCTs found that intrathecal morphine displayed inferior postoperative analgesia and morphine-sparing effects than LIA followed by repeated postoperative intra-articular injection (Essving 2011; McCarthy 2019).

PROSPECT Recommendations

• Intrathecal morphine (100 μg) may be considered only in hospitalised patients when surgery is performed under spinal anaesthesia and in the rare situation wherein both ACB and LIA are not possible.
• Intrathecal morphine carries bothersome side effects (pruritus, nausea, urinary retention), which interfere with postoperative recovery (Tang 2017; Li 2016).
• Although intrathecal morphine has been demonstrated to be more beneficial than placebo, it has not been shown to be superior to regional analgesic techniques (peripheral nerve blocks and LIA) (Sites 2004; Frassanito 2010; Olive 2015; Tarkkila 1998; Qi 2020). Interpretation of studies is hindered as most did not use LIA and had a variable use of basic analgesics.
• Intrathecal morphine is not suitable for ambulatory TKA because of potential concerns of respiratory depression, albeit remote.

TKA-specific evidence

Data table: Epidural analgesia for pain management after TKA

Study details:

• One meta-analysis compared epidural analgesia after TKA with peripheral nerve blocks (Gerrard 2017), and included 12 RCTs that assessed epidural analgesia vs FNB ± sciatic nerve block or vs lumbar plexus block. Of these, eight RCTs fulfilled PROSPECT criteria (Singelyn 1998; Capdevila 1999; Adams 2002; Davies 2004; Barrington 2005; Zaric 2006; Campbell 2008; Sakai 2013).
  • Epidural analgesia included local anaesthetic alone or in combination with a lipophilic opioid (fentanyl and sufentanil) and/or epinephrine or clonidine.
  • Almost all the studies (7/8) used basic analgesic treatment like paracetamol and/or NSAID.
• One meta-analysis compared epidural analgesia to LIA and included seven RCTs (Li 2018). Six RCTs met the criteria for inclusion in the PROSPECT review (Klasen 1999; Andersen 2010; Spreng 2010; Binici Bedir 2014; Tsukada 2014; Kasture 2015).
  • Three reported administration of high-volume LIA (60 to 100 ml) and three mentioned the use of intra-articular injection.
  • In five of six studies, the epidural analgesia included local anaesthetic with or without opioid.
  • Five of six studies reported the use of NSAID as the basic analgesic regimen.

Arguments against…

• There was no clinically significant difference in pain scores between epidural analgesia and peripheral nerve blocks at any time point from 0 to 48 h (Singelyn 1998; Capdevila 1999; Adams 2002; Davies 2004; Barrington 2005; Zaric 2006; Campbell 2008; Sakai 2013).
• Only one of five RCTs reported postoperative opioid sparing in favour of epidural analgesia when compared with continuous FNB (Barrington 2005).
• Epidural analgesia was associated with significantly higher risk of PONV, hypotension and urinary retention than peripheral nerve blocks (Gerrard 2017).
• Overall, results demonstrated equivalent analgesic efficacy of epidural analgesia and LIA (Klasen 1999; Spreng 2010; Binici Bedir 2014; Kasture 2015). However, epidural analgesia was less effective than LIA in two of six trials (Andersen 2010; Tsukada 2014).
• Epidural analgesia and LIA showed no differences in postoperative opioid consumption (Klasen 1999; Andersen 2010; Spreng 2010).
• Epidural analgesia was associated with an increased incidence of PONV, increased length of stay, and reduced mobility (lower range of motion) (Li 2018).

PROSPECT Recommendations

• Epidural analgesia is not recommended for management of postoperative pain after TKA due to potential adverse effects precluding rapid recovery.

TKA-specific evidence

Data table: Peripheral nerve blocks (PNB) for pain management after TKA

Study details:

• Sixteen systematic reviews and meta-analyses reported on FNB in TKA. Included RCTs compared FNB with:
  • Intrathecal morphine (Tang 2017; Li 2016)
  • Epidural analgesia (Gerrard 2017)
  • ACB (Dong 2016; Gao 2017; Kuang 2017; Kuang 2016; Li 2016; Wang 2017; Zhang 2019; Zhao 2016)
  • LIA (Mei 2015; Yun 2015; Albrecht 2016; Zhang 2017; Zhang Y 2018).
• Three meta-analyses investigated use of SNB in addition to FNB (Abdallah 2016; Grape 2016; Zorrilla-Vaca 2018) and three meta-analyses evaluated the addition of either SNB or LIA to FNB (Zhang 2017; Li 2016; Ma 2017). Seven of the included studies met the PROSPECT criteria (Gi 2014; Nagafuchi 2015; Safa 2014; Tanikawa 2014; Mahadevan 2012; Uesugi 2014; Spangehl 2015).
  • Basic analgesics were used in the included studies.

Arguments for…

• Results showed that FNB displayed similar analgesic efficacy to intrathecal morphine, epidural analgesia, ACB and LIA (Tang 2017; Li 2016; Gerrard 2017; Dong 2016; Gao 2017; Kuang 2017; Kuang 2016; Li 2016; Wang 2017; Zhang 2019; Zhao 2016; Mei 2015; Yun 2015; Albrecht 2016; Zhang 2017; Zhang Y 2018).
• FNB was associated with reduced incidence of side effects compared with intrathecal morphine and epidural analgesia (Tang 2017; Li 2016; Gerrard 2017).
• Results showed no overall difference between SNB and LIA in terms of postoperative analgesia and opioid consumption (Gi 2014; Nagafuchi 2015; Safa 2014; Tanikawa 2014; Mahadevan 2012; Uesugi 2014; Spangehl 2015).

Arguments against…

• Importantly, FNB carries an increased risk of quadriceps weakness, particularly when a continuous infusion technique is used (Memtsoudis 2014). Quadriceps weakness is worse with FNB than ACB (Elkassabany 2016).
• Addition of SNB to FNB or ACB did not provide any additional clinically relevant analgesic benefits and no significant decrease of postoperative opioid use.
• Two studies assessed long-term benefits of SNB and found no benefits at 3 and 6 weeks (Safa 2014; Tanikawa 2014).
• An important concern of SNB includes the potential for motor and sensory deficit of the lower leg, with reduction of foot mobility, which may impair early mobilisation and might delay postoperative recovery.

PROSPECT Recommendations

• Femoral nerve block is not recommended for management of postoperative pain after TKA due to evidence of a negative impact on functional recovery.
• Sciatic nerve block is not recommended for management of postoperative pain after TKA due to evidence of a negative impact on functional recovery.