- Total knee arthroplasty (TKA) is associated with significant postoperative pain, and effective pain control affects postoperative rehabilitation and long-term outcomes.
- Several publications provide general opinions and guidelines for pain management after TKA but they often lack critical assessment of included studies.
- Therefore, the optimal combinations of analgesic interventions remain unclear.
- The aim of this review is to provide clinicians with recommendations for pain management after unilateral primary TKA with particular attention to early rehabilitation and mobilisation.
- This approach reports true clinical effectiveness by balancing the invasiveness of the analgesic interventions and the degree of pain after surgery, and also balancing efficacy and adverse effects.
The occurrence of severe knee pain, generally caused by osteoarthritis, has been increasing because of the aging population and an increase in pro-inflammatory conditions, such as obesity. Symptomatic knee pain represents a burden for modern healthcare systems. When conservative treatments, such as physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular steroid, hyaluronic acid injections and peri-articular infiltrations of genicular nerves have failed, total knee arthroplasty is considered the most effective treatment.1 Not surprisingly, the number of TKA performed is constantly increasing.
As TKA is painful, frequently performed and involves a reproducible surgical technique, approaches to the management of peri-operative pain have been extensively studied. There are numerous published systematic reviews and meta-analyses assessing single, individual, analgesic interventions for TKA.2–6 Furthermore, several publications provide general opinions and guidance for pain management after TKA.7–9 However, TKA remains a major orthopaedic procedure that is associated with severe postoperative pain and may lead to persistent pain in 15 to 20% of patients.10,11 Importantly, the best combination of interventions for optimal multimodal analgesia remains unclear.12
The PROSPECT (PROcedure SPEcific Postoperative Pain ManagemenT) Working Group is a global collaboration of surgeons and anaesthesiologists formulating procedure-specific recommendations for pain management after common but potentially painful, operations.13 The PROSPECT approach is unique in that the available evidence is critically assessed for current clinical relevance, balanced with regards to the use of simple nonopioid analgesics, such as paracetamol and NSAIDs. This approach reports true clinical effectiveness by balancing the invasiveness of the analgesic interventions and the degree of pain after surgery, and also balancing efficacy and adverse effects. In addition, attention is paid to early rehabilitation and mobilisation. The aim of the present review was to update the 2009 recommendations using a modified PROSPECT approach for pain management after unilateral primary TKA. This included identifying systematic reviews and meta-analyses evaluating analgesic interventions for TKA, and then critically assessing the individual randomised controlled trials (RCTs) that were already evaluated for risk bias. Only the RCTs that conformed to aforementioned Prospect criteria were then used to develop recommendations.
Given the impressive number of RCTs that have been published to date regarding pain management after TKA, the PROSPECT group decided to critically assess the published systematic reviews and meta-analyses evaluating individual analgesic interventions for TKA.14,15 The systematic reviews and meta-analyses included in this review were performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) recommendations including assessments of risk of bias of RCTs using the Cochrane Collaboration tool.16 The PROSPECT Group decided to capitalise on previous work and not repeat much of the arduous basic work, performing risk bias assessments. This approach is termed Adolopment by the grades of recommendation, assessment, development and evaluation (GRADE) Working Group.17 This provides advantages of selectively combining adoption, adaptation and de novo development of guidelines recommendations whether updated or new.
A literature search was performed for systematic reviews and meta-analyses evaluating analgesic interventions for pain management in patients undergoing TKA published between January 2014 and December 2020. Although we performed the literature search from January 2014 to December 2020, the RCTs in the included systematic reviews/meta-analyses were those available since the database inception. The EMBASE, MEDLINE, PubMed and Cochrane Databases were queried using the search terms “knee replacement” OR “knee arthroplasty” AND “postoperative pain” AND “meta-analysis” OR “systematic review”. Only the publications assessing systemic analgesic interventions [paracetamol, NSAIDs, cyclo-oxygenase (COX)-2 specific inhibitors, gabapentinoids, corticosteroids, ketamine, α2-adrenergic agonists, opioids and others] and regional techniques [epidural analgesia, spinal opioids, peripheral nerve blocks, local infiltration analgesia (LIA) and others] were considered. Anaesthetic techniques (general anaesthesia and neuraxial anaesthesia), surgical techniques including tourniquet use and nonpharmacological interventions were not reviewed.
Each RCT included in the selected publication was critically evaluated according to the PROSPECT methodology including clinical relevance of the analgesic effects of the intervention according to pain intensity measured by validated pain scales, such as the visual analogue scale (VAS) and numerical rating scale (NRS). Of note, the differences in pain scores should be at least 1/10 cm or 10/100 mm on the VAS or 1/10 point on VAS/NRS. However, 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. Particular attention was paid to the added benefits of the co-analgesics (paracetamol and NSAIDs or COX-2 specific inhibitors) in addition to LIA because of their well documented analgesic effects, being simple, inexpensive and safe (NICE guidelines).18 The primary outcome was the degree of pain as determined by pain scores. The secondary outcome measures included reduction of the side effects of opioids and effects of the treatment on passive knee mobilisation and active rehabilitation, whenever available. In addition, the invasiveness of the analgesic technique and the specific side effects of the treatment itself were considered. Finally, the current clinical relevance of the interventions was considered. Of note, determination of safety of an analgesic intervention was based on all types of studies (RCTs and cohort studies) from all types of procedures.
The proposed recommendations along with the extraction tables that included details of individual RCTs were sent to the PROSPECT Working Group for review and comments and a modified Delphi approach was used to achieve a consensus. Following this, the lead authors drafted the final document that was ultimately approved by the Working Group.
A total of 6 meta-analyses19–24 assessing the analgesic effect of oral and intravenous paracetamol were identified with a total of 22 included studies. Of these, only two RCTs25,26 fulfilled PROSPECT inclusion criteria (Table S1, https://links.lww.com/EJA/A701), other studies being either retrospective cohort studies or mixed TKA and total hip arthroplasty (THA). No side effects related to the treatment were reported. On the basis of the assessments of the included RCTs, paracetamol is recommended preoperatively or intra-operatively and should be continued postoperatively.
Nonsteroidal anti-inflammatory drugs including cyclo-oxygenase-2-specific inhibitors
Two meta-analyses have assessed the efficacy and safety of NSAIDs in the context of TKA. Du and Gu27 assessed the effects of parecoxib versus saline, whereas Fillingham et al.28 analysed the effects of NSAIDs. From these two meta-analyses, six RCTs of good quality, all assessing peri-operative COX-2-specific inhibitors administration in TKA were considered for analysis (Table S1, https://links.lww.com/EJA/A701).29–35 In all the included RCTs, COX-2-specific inhibitors reduced postoperative pain scores at rest and during mobilisation and reduced postoperative opioid requirements but without decreasing opioid-related adverse effects like postoperative nausea and vomiting (PONV). It is worth noting that the benefits of COX-2-specific inhibitors, for both their analgesic and opioid-sparing effects, are observed even with concomitant paracetamol administration or LIA. Therefore, NSAIDs or COX-2-specific inhibitors are recommended preoperatively or intra-operatively and should be continued postoperatively.
Altogether 12 systematic reviews and meta-analyses were identified, of which 7 focused only on TKA, whereas 5 were combined trials of THA and TKA.14 From these meta-analyses, six RCTs were included. All RCTs included some form of combination of paracetamol, NSAID/COX-2-specific inhibitors and LIA (Table S1, https://links.lww.com/EJA/A701). The three RCTs assessing a single preoperative dose showed a reduction in pain, postoperative analgesic consumption and PONV.36–38 There were no safety issues. Similarly, the repeat dosing studies37,39–41 showed a significant reduction in postoperative pain up to 48 h together with reduction in postoperative opioid requirements and PONV. No safety issues were demonstrated but the total number of glucocorticoid-treated patients was small (n = 150). The data do not allow recommendations for a specific dose as no dose-finding studies have been performed but the single preoperative dose regimens have used a dose between 10 to 25 mg of dexamethasone equivalents. The safety of a single preoperative glucocorticoid dose is supported by a large before and after implementation study42 and a systematic review.43 However, no such safety studies are available for repeat-dosing regimens. Although several RCTs on local administration of glucocorticoids together with LIA are available,14 interpretation is hindered by the lack of a systemic dose for control. In summary, single preoperative or intra-operative dose of dexamethasone (≥10 mg, i.v.) is recommended, being simple, safe and effective even with concomitant use of paracetamol, NSAIDs, COX-2 specific inhibitors and LIA.
Gabapentinoids (gabapentin and pregabalin)
A total of six meta-analyses assessed the analgesic effects of gabapentinoids in patients undergoing TKA.15 Four systematic reviews assessed gabapentin administration,44–47 which included eight RCTs. Of these eight RCTs, four were included for evaluation (Table S2, https://links.lww.com/EJA/A701).48–51 There was significant variation in the dose (preoperative ranged from 600 1300 mg and postoperative up to 1300 mg, twice daily), timing of preoperative administration and duration of postoperative administration. The postoperative analgesic regimen included NSAID or COX-2-specific inhibitors ± paracetamol in only three RCTs, whereas a perineural catheter was used in one RCT. Opioids were used as rescue.
Four systematic reviews/meta-analysis,47,52–54 including a total of eight RCTs, assessed pregabalin administration, of which six RCTs were included for evaluation (Table S2, https://links.lww.com/EJA/A701).55–60 There was significant variation in the dose (preoperative: 50 to 300 mg and postoperative: 0 to 300 mg, twice daily), timing of preoperative administration (30 min to 24 h, preoperatively) and duration of postoperative administration (single dose to 6 weeks).55,56,58,59
Regional anaesthesia (combined spinal epidural or spinal alone) was used in all included RCTs. Most RCTs (n = 6) used regional analgesia, whereas one RCT administered i.v. patient-controlled analgesia (PCA). Supplementary analgesia included intrathecal opioid (n = 4; fentanyl, n = 1 and morphine, n = 3), femoral nerve block (FNB) (n = 2) and LIA (n = 1). Opioids were used as rescue.
In summary, gabapentinoids are not recommended because of lack of clinically relevant analgesia when combined with paracetamol, NSAID/COX-2 specific inhibitors and LIA and well documented risks of side effects.
Three meta-analyses assessed analgesic effects of peri-operative ketamine after TKA61 or after both TKA and THA.62,63 Five RCTs assessed intravenous low doses of ketamine after TKA (other studies assessed intra-articular, epidural or only postoperative PCA, or assessed ketamine use in THA). In three RCTs, ketamine was used as a bolus dose (0.5 mg kg−1) and a continuous infusion of 4 to 6 μg kg−1 min−1 until the end of surgery, whereas in two RCTs, a ketamine bolus (0.5 mg kg−1) was followed by a continuous infusion of 1.5 to 3.0 μg kg−1 min−1 over 48 h after surgery (Table S2, https://links.lww.com/EJA/A701). In all these studies, ketamine was compared with placebo, whereas one RCT also included a nefopam group.64 In two RCTs, ketamine administration displayed significant analgesic effect at rest and during mobilisation independent of the duration of administration but PCA morphine alone was available for postoperative analgesia and nonopioid analgesics were not administered.64,65 Ketamine was more effective than nefopam in reducing postoperative pain in a single study comparing ketamine to nefopam.64 When a basic analgesic regimen (NSAID, paracetamol and/or LIA)66 or continuous FNB67 was used, systemic ketamine did not significantly reduce postoperative pain intensity. Although opioid-sparing was observed in four of five RCTs,64,65,67,68 it did not affect opioid side effects (PONV). In two RCTs,64,67 ketamine was associated with faster passive rehabilitation. Finally, four RCTs66–69 questioned the long-term benefits of peri-operative ketamine without clear evidence regarding chronic pain development.
In summary, ketamine, intra-operatively and/or postoperatively, is not recommended because of lack of evidence when using a basic analgesia regimen (paracetamol NSAID's/COX-2 specific inhibitors and LIA).
Systemic α2-adrenergic agonists
One meta-analysis evaluated the efficacy and safety of intravenous dexmedetomidine in patients undergoing TKA and THA.70 After exclusion of RCTs where dexmedetomidine was used in THA and those where it was added to local anaesthetic in perineural blocks, two RCTs remained for analysis (Table S2, https://links.lww.com/EJA/A701). A dexmedetomidine bolus dose of 0.5 to 1.0 μg kg−1 followed by a continuous infusion of 0.1 to 0.5 μg kg−1 h−1 until the end of surgery administered to patients undergoing TKA under spinal anaesthesia was compared either with placebo71 or to propofol sedation.72 The primary endpoint of both RCTs was postoperative opioid-sparing effect. Dexmedetomidine significantly decreased postoperative morphine as well as itching (5 versus 30%) and PONV (5 versus 30%) in the study of Chan et al.71 and significantly decreased postoperative fentanyl consumption in the study of Shin et al.72 but without affecting the use of postoperative antiemetics. Although basic analgesics (paracetamol and NSAIDs) were used in both RCTs, dexmedetomidine only reduced pain intensity in one of the two RCTs72 precluding any conclusion about its analgesic effect. In the later study,72 patients also received femoral nerve block, LIA, pregabalin and dexamethasone.
In summary, dexmedetomidine is not recommended as it was used for sedation during spinal anaesthesia and because of limited and conflicting evidence and concerns of adverse effects, such as bradycardia and hypotension.
Intrathecal morphine has been demonstrated to be better than placebo (Table S1, https://links.lww.com/EJA/A701).73–84 Three meta-analyses including four RCTs compared intrathecal morphine with FNB85,86 and with LIA.87 The dose of intrathecal morphine varied between 100 and 300 μg (Table S1, https://links.lww.com/EJA/A701). Compared with single shot FNB, there was no clinically significant difference in postoperative pain at rest or during mobilisation and no postoperative opioid-sparing effect.88,89 Similar observations were made for the comparison with continuous FNB.78,90 Although postoperative opioid consumption was less in the immediate postoperative period (6 to 12 h), Intrathecal morphine increased opioid consumption at 18 to 24 h.78 In all studies, intrathecal morphine was associated with increased pruritus and decreased patient satisfaction. In a more recent meta-analysis,87 intrathecal morphine was compared with LIA in both TKA and THA. The four RCTs in TKA patients showed no differences in postoperative analgesia and opioid-sparing with intrathecal morphine (100 to 300 μg).91–94 In two RCTs, intrathecal morphine displayed inferior postoperative analgesia and morphine-sparing effects than LIA followed by repeated postoperative intra-articular injection.91–94
In summary, intrathecal morphine (100 μg) may be considered only for hospitalised patients receiving spinal anaesthesia and whenever regional analgesia (ACB and LIA) is not possible.
Two meta-analyses assessed epidural analgesia after TKA, in comparison to peripheral nerve blocks95 or to LIA.96 In the former,95 12 RCTs were included, which compared epidural analgesia either with FNB +/- sciatic nerve block (SNB) or with lumbar plexus block. Of these, eight RCTs fulfilled PROSPECT criteria.97–104 Epidural analgesia included the administration of a 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. 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. Only one study among the five RCTs reporting postoperative opioid sparing in favour of epidural analgesia when compared with continuous FNB.101 Epidural analgesia was associated with significantly higher risk of PONV, hypotension and urinary retention.95
The meta-analysis96 comparing epidural analgesia to LIA included seven RCTs (one RCT was excluded as it was performed in patients undergoing bilateral TKA). In the six included RCTs (Table S2, https://links.lww.com/EJA/A701),105–110 three reported the administration of high-volume LIA (60 to 100 ml) whereas three mentioned the use of intra-articular injection. In five of six studies, the epidural analgesia included local anaesthetic with or without opioid. Also, five of six studies reported the use of a NSAID as the basic analgesic regimen. Results demonstrated the equivalent analgesic efficacy of epidural analgesia and LIA. Interestingly, epidural analgesia was less effective than LIA in two of six trials.106,109 There were no differences between epidural analgesia and LIA for postoperative opioid consumption. Epidural analgesia was associated with an increased incidence of PONV and increased length of stay, and was less efficient with regards to mobilisation [lower range of motion (ROM)].
In summary, intra-operative and postoperative epidural analgesia, despite analgesic effects is not recommended because of potential adverse effects (reduced mobility, hypotension, urinary retention) precluding rapid recovery.
Femoral nerve block
A total of 16 systematic reviews and meta-analyses reporting FNB in TKA were identified. Postoperative analgesia and opioid-sparing effects of FNB have been compared with intrathecal morphine85,86 (two studies, refer to the intrathecal morphine section), epidural analgesia 95 (one study, refer to the Epidural analgesia section), ACB (eight studies, refer to the Adductor Canal Block section)111–118 and LIA119–123 (five studies, refer to the Local Infiltration Analgesia section). To summarise, FNB displays similar analgesic efficacy to intrathecal morphine, epidural analgesia ACB and LIA. FNB shows less side effects than intrathecal morphine and epidural analgesia. Importantly, FNB carries an increased risk of quadriceps weakness, particularly when a continuous infusion technique is used.124 Quadriceps weakness is worse with FNB than ACB.125 Therefore, FNB (single shot and/or postoperative infusion), despite analgesic effects is not recommended because of reduced mobility from muscle weakness which can preclude rapid recovery.
Sciatic nerve block
Three meta-analyses assessed the analgesic efficacy of SNB in addition to FNB126–128 and three meta-analyses evaluated benefits of adding either SNB or LIA to a FNB.121,129,130 Among nine studies included in these meta-analyses, seven RCTs met PROSPECT criteria (Table S2, https://links.lww.com/EJA/A701).131–137 All the RCTs showed no difference between SNB and LIA in term of postoperative analgesia and opioid consumption. Addition of SNB to the FNB or ACB did not provide any additional clinically relevant analgesic benefits and also no significant decrease of postoperative opioid use. Two studies assessed long-term benefits of SNB, and found no benefits at 3 and 6 weeks.131,132 Of note, basic analgesics were used consistently in the included studies. 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. Therefore, SNB is not recommended because of concerns of quadriceps weakness and delayed ambulation.
Adductor canal block
A total of 26 systematic reviews and meta-analyses were identified reporting ACB in TKA [ACB versus FNB (n= 8),111–118 ACB versus LIA (n = 10),138–147 and ACB technique (n = 7)].148–152 Five RCTs compared ACB with saline ACB (either bolus or repeated boluses or continuous infusion) (Table S1, https://links.lww.com/EJA/A701).153–157 Of these, two RCTs evaluated rescue (postoperative) ACB in patients with severe postoperative pain either at 6 h or on postoperative day 2.154,155 A multimodal analgesic protocol was used in all studies. In all the RCTs, ACB significantly reduced pain associated with knee flexion and mobilisation. However, a decrease in postoperative opioid use was inconsistent with no impact on PONV. When administered in patients enduring severe postoperative pain, ACB provided pain relief at rest and during knee flexion with a duration of up to 6 h.
Four RCTs compared single shot ACB with single shot FNB in terms of postoperative pain relief and quadriceps muscle motor function (Table S1, https://links.lww.com/EJA/A701).158–161 No differences in analgesic effects and opioid use were found between the two techniques. ACB allowed superior knee function and mobilisation by sparing quadriceps muscle function. Eight RCTs compared continuous ACB with continuous FNB without significant differences in postoperative analgesia and opioids use. Here also, ACB allowed better preservation of knee function than FNB by sparing the quadriceps.115
Seven RCTs assessed single shot injection ACB with continuous ACB.162–168 The majority of the studies also used a multimodal analgesic protocol but rarely LIA. In this setting, no significant benefit of continuous ACB infusion was demonstrated in terms of analgesia and use of rescue opioids (six of seven RCTs). One study questioned the benefit of 48 h ACB infusion over 24 h or single shot.165 One study also compared ACB bolus and continuous infusion using local anaesthetic alone, with single shot ACB including a mixture of 20 ml bupivacaine 0.25% with clonidine, dexamethasone and buprenorphine.163 No important differences were found between the groups.
A total of eight RCTs compared ACB with LIA54,169–175 (six of them included in a recent meta-analysis142). In four RCTs, ACB had greater analgesic efficacy than LIA, particularly regarding dynamic pain, whereas in others, ACB was not inferior to LIA.169,172,174,175 Postoperative opioid consumption was similar between ACB and LIA in four RCTs, whereas in others opioid-sparing was greater but without reduction of opioid-related adverse effects. The majority of the RCTs used multimodal analgesia with paracetamol, COX-2-specific inhibitor, gabapentinoid and systemic opioid. There was a significant variability in the LIA volume (40 and 100 ml, five of eight RCTs) or solution (three of eight RCTs).
Twelve studies evaluated the benefits of combining ACB with LIA in comparison with either technique alone. Among them, five RCTs compared a combination of ACB and LIA to ACB alone.169–172,176 All studies included a multimodal analgesic regimen. In this setting, ACB alone was equivalent (three of five) or inferior (two of five) to the combination of ACB and LIA in term of analgesia and opioid consumption. Five RCTs compared a combination of ACB and LIA to LIA alone.169,172,176–178 The combination of ACB and LIA was superior to LIA for pain control only during the first 24 h. All the studies used a multimodal analgesic regimen, except one177 where patients received only paracetamol and morphine but no NSAIDs. Regarding opioid-sparing effect, the combination of ACB and LIA was not superior to LIA alone (five of five RCTs).
In summary, a single shot ACB is recommended and preferably combined with LIA. Continuous ACB is not recommended because of inconsistent benefits.
Local infiltration analgesia
Most meta-analyses assessing the analgesic efficacy of LIA have compared it with other regional analgesic techniques. All meta-analyses 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 considered efficacy of LIA versus no injection or placebo.179–183 In a systematic review by Seangleulur et al.,181 peri-articular but not intra-articular injection reduced pain at rest at 24 and 48 h and increased range of motion (n = 7 RCTs). Twenty meta-analyses111,112,114–116,118–120,123,125–127,129,130,146,184–188 compared the analgesic benefits of LIA with various peripheral nerve blocks.4 The RCTs comparing LIA with ACB have been reported above. There were 11 meta-analyses compared LIA with FNB with mixed results.5,119,120,123,188,189 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.179,181 However, deep knee infection was reported in 3 out of 735 patients receiving a catheter included in the meta-analysis of Seangleulur et al.181 Similar conclusions were drawn by Zhang et al. who included seven RCTs in their meta-analyses183 and by Sun et al.190 who included 10 RCTS in their meta-analyses. Another meta-analysis191 found that the use of continuous peripheral nerve blocks (FNB or ACB) does not provide superior analgesic benefit over single shot LIA. The potential benefits of using liposomal bupivacaine has been evaluated in six meta-analyses125,192–197 and a Cochrane review.198 The role of liposomal bupivacaine in LIA for TKA remains unclear because of conflicting evidence.
Overall, the included RCTs showed improved pain relief and reduced opioid requirements with LIA. In addition, LIA allowed earlier functional recovery, range of motion, time to straight leg raise and 90° knee flexion but influence on hospital length of stay was inconsistent. Compared with control group, the catheter LIA technique was associated with reduced pain and opioid requirements up to 72 h postoperatively but there are concerns of infection. Of note, cost-effectiveness of LIA has been supported by the NICE guidelines.18
In summary, peri-articular LIA is recommended. However, continuous LIA or continuous intra-articular local anaesthetic infusion are not recommended because of inconsistent benefits and concerns of potential infection. The optimal site and volume for peri-articular administration of drugs remains unclear because of heterogeneity between the studies.
This review examined the effects of analgesic interventions for the management of pain after unilateral, primary TKA. The selected RCTs were critically assessed according to the PROSPECT methodology, which goes beyond evaluating the statistical differences in pain scores and opioid use.13 Considerable attention was given to the use of basic analgesics (paracetamol and NSAIDs), the balance of analgesic efficacy and adverse effects of the intervention and current clinical relevance.
The use of NSAIDs or COX-2-specific inhibitors administered either preoperatively or intra-operatively, and continued postoperatively is recommended. This is in agreement with the strong recommendation made in a recent meta-analysis by Fillingham et al.28 Both NSAIDs and COX-2 specific inhibitors have been reported to control pain and promote rehabilitation for 3 to 6 weeks after TKA.34,199 In a large population-based study involving 1 028 069 knee arthroplasties, NSAIDs and COX-2-specific inhibitors were found to be the most effective means of improving peri-operative outcomes and reducing resource utilisation (19% fewer respiratory and 26% fewer gastro-intestinal complications, up to 18.5% reduction in opioid prescriptions and 12.1% reduction in hospital length of stay).200,201 Of note, COX-2-specific inhibitors possess similar analgesic efficacy to NSAIDs but with no effects on platelet function, and thus, could be administered preoperatively. A recent meta-analysis including a large number of patients receiving various types of NSAIDs and undergoing a variety of surgical procedures found that NSAIDs are unlikely to be the cause of postoperative bleeding complications.202 To date, no safety concerns have been reported but prescribers need to remain vigilant as the typical older TKA population may be at a higher risk of adverse effects.28 Although paracetamol alone has limited analgesic and opioid-sparing efficacy, moderate evidence supports its use for peri-operative pain management after TKA.24 It is a low-cost and low-risk option and more importantly, it demonstrates an interesting opioid-sparing effect when combined to NSAIDs.203,204
Glucocorticoids for a long time have been considered as the ‘ultimate anti-inflammatory drugs’, and there has been increased attention given to their peri-operative use to provide PONV prophylaxis, analgesia and fatigue reduction.14 Glucocorticoid administration was beneficial both in terms of pain relief and opioid-sparing effects even when used as a component of multimodal analgesic regimen. Therefore, a single intra-operative intravenous dexamethasone dose is recommended, being simple, safe and effective with concomitant use of basic analgesics and LIA.14 It is worth noting that glucocorticoids represent a highly valuable alternative for some patients who have contraindications to NSAIDs and COX-2-specific inhibitors. However, the safety of repeated doses of glucocorticoids to improve postoperative recovery remains questionable. The optimal dose of preoperative dexamethasone still remains undetermined as the dose used in the different RCTs varied significantly from 10 to 25 mg.14 However, a previous meta-analysis in a mixed surgical population has reported that dexamethasone greater than 0.1 mg kg−1 was an effective adjunct to multimodal strategies.205 In the TKA setting, a recent study reported a significant reduction of postoperative pain from 12 to 21 h when a preoperative dose of 0.15 mg kg−1 dexamethasone was used.206 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.42,43
Gabapentinoids have been reported to reduce postoperative pain scores and opioid consumption. However, a critical analysis of the published literature shows major flaws that limit the interpretation for the recommended use of peri-operative gabapentinoids in TKA.15 Furthermore, there are several concerns of potential adverse effects of gabapentinoids, such as sedation, dizziness and visual disturbances that might interfere with early ambulation. These concerns are of even greater importance when gabapentinoids are combined with opioids,207,208 which are typically necessary after TKA despite use of nonopioid analgesic strategies. Therefore, gabapentinoids are not recommended for TKA.
As TKA may be performed under spinal anaesthesia, intrathecal morphine might seem to be a good choice for control of early (first 12 to 24 h) postoperative pain. It is easier to perform compared with regional blocks like FNB or ACB, which require skill and training and may be time consuming. However, intrathecal morphine carries bothersome side effects (pruritus, nausea, urinary retention), which interfere with postoperative recovery.85,86 Also, the administration of intrathecal morphine does not seem to provide superior benefit to LIA.87 The interpretation of intrathecal morphine studies is hindered by the fact that most studies did not use LIA and had a variable use of basic analgesics. 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). Also, intrathecal morphine was associated with a rebound increase in postoperative opioid use at 18 to 24 h.78 Furthermore, although intrathecal morphine 100 μg is safe with respect to respiratory depression,209,210 it is associated with bothersome side effects like PONV, pruritus and urinary retention. These potential adverse effects may delay ambulation and oral intake, and influence patient satisfaction. Given that sufficient pain relief may be achieved with the combination of paracetamol, NSAIDs, dexamethasone and LIA, and also the possibility of bothersome adverse effects, the use of intrathecal morphine remains controversial. Of note, intrathecal morphine is not suitable for ambulatory TKA because of potential concerns of respiratory depression, albeit remote. Therefore, low-dose intrathecal morphine (100 μg) may only be considered in hospitalised patients when the surgery is performed under spinal anaesthesia and in the rare situation wherein both ACB and LIA are not possible.
Although epidural analgesia provides effective pain relief, and was once considered a standard of care for managing pain after TKA, it suffers several limitations, particularly delayed time to ambulation.211,212 Several RCTs found no significant differences between epidural analgesia and peripheral nerve blocks at any time point until 48 h after surgery. Also, RCTs comparing epidural analgesia and LIA favoured the use of LIA, as it provides similar pain relief and does not negatively affect early rehabilitation. Therefore, epidural analgesia is not recommended for management of pain after TKA. The analysis of the RCTs using PROSPECT criteria is in agreement with the conclusions of the published meta-analysis and systematic reviews.95,96
FNB was widely used to control postoperative pain and opioid consumption after TKA,3,5 although it only covers pain from the antero-medial part of the knee, leaving the posterior knee uncovered. However, FNB induces quadriceps weakness, which, combined with the muscle loss after knee surgery, may impair postoperative mobilisation.115 Also, continuous blocks have been incriminated in the risk of falls.213 Therefore, it has been replaced with ACB, which demonstrates similar analgesic efficacy to FNB but seems to better preserve quadriceps function.214 Single shot ACB has been used as a rescue block to control pain on the first or second postoperative day when it reduced pain at rest (92% success) but less so during active flexion (22% success).155 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.
Since its first description in 2008 by Kerr and Kohan,215 LIA has demonstrated consistent benefits in terms of postoperative analgesia and opioid-sparing effect, allowing faster mobilisation and in some case earlier discharge when compared with ‘older’ analgesic techniques like intrathecal morphine and epidural analgesia. Of note, unlike other analgesic interventions, in which we used assessment of individual RCTs to determine the recommendation, the conclusions of meta-analyses were accepted as most included RCTs conformed to Prospect inclusion criteria. The NICE expert group reviewed evidence for best anaesthesia and analgesia techniques for knee replacement including costs involved with these techniques and recommends LIA and peripheral nerve blocks.18 Also, LIA was considered cost-effective whereas nerve blocks were cost-effective only if administered by an experienced anaesthesiologist.18 Overall, LIA is an effective, simple and minimally invasive analgesic technique, which should be considered as ‘basic’ analgesia in combination with paracetamol and NSIADs/COX-2-specific inhibitors. Of note, there was no additional analgesic benefit of adding posterior capsular infiltration to LIA,216 particularly as it is not without risk of intravascular and neurological injury.
LIA generally includes infiltration of different knee compartments with a cocktail consisting of local anaesthetic (typically, bupivacaine or ropivacaine) and one or more drugs, such as epinephrine, ketorolac, clonidine, glucocorticoids and morphine. The addition of ketorolac, which was part of the original mixture described by Kerr and Kohan,215 was claimed to provide further reduction of early postoperative pain scores, on top of NSAIDs and paracetamol,217,218 but this is debatable when compared with concomitant use of a systemic dose of NSAID.107,179 Similarly, the need for epinephrine in LIA is questionable.219 The addition of glucocorticoids to local anaesthetic mixture has also been studied without definitive conclusion and without direct comparison with the systemic administration of the drug.14,220 The use of liposomal bupivacaine has been evaluated in several RCTs but it did not demonstrate benefits over plain bupivacaine with regards to analgesic efficacy221 or postoperative analgesic outcomes, functional outcomes and safety.222 The risk of local anaesthetic systemic toxicity with LIA has been evaluated in several studies but not reported to be a problem. These studies used high-dose ropivacaine (300 to 400 mg), and reported free plasma levels of ropivacaine ranging from 0.37 to 1.35 μg ml−1, which are lower than the toxicity threshold concentration of 1.5 μg ml−1.223
The present review suffers from the limitations inherent in the included studies just like any other meta-analysis or systematic review. Also, these recommendations do not address pain management in patients undergoing re-operation or associated secondary surgical procedures. Neither did this review addresses one of the key goals of peri-operative pain management, patient stratification.224 Also, several sub-groups of patients still experience severe acute postoperative pain despite standardised postoperative analgesia, such as those with preoperative chronic pain conditions, and those taking preoperative opioids.225,226 Unfortunately, those patients remain excluded from most RCTs, so studies aiming to assess the benefit of specific intervention are too scarce. In addition, a modified methodology was utilised when the literature search was performed for systematic reviews and meta-analyses that evaluate analgesic interventions rather than searching individual RCTs. Thus, it is possible that some of the RCTs evaluating newer regional analgesia techniques for TKA (iPACK block, cryoneurolysis, genicular nerve block, saphenous nerve block methocarbamol and others) may not be included. However, based on the PROSPECT methodology, these analgesic interventions could not have been recommended because of limited evidence. A novel block, ‘iPACK’, which targets the interspace between the popliteal artery and the capsule of the posterior knee, has promise as a good compromise between posterior knee analgesia and knee function.227 However, unlike LIA, which is easy to perform and has proven to be very safe and effective, iPACK uses ultrasound techniques that requires some expertise and is time consuming. A recent MRI and cadaveric study seems to show that saphenous nerve block is feasible from within the knee, and thus could be performed by the surgeon.228
It was observed that administration of basic analgesics (NSAIDs or COX-2-specific inhibitors combined with paracetamol) was missing in a significant number of RCTs, which precludes an objective evaluation of the benefits of the analgesic intervention studied.229 There was considerable heterogeneity between studies with regards to anaesthetic and analgesic techniques as well as variability in outcomes assessed. TKA patients represent a specific group of patients presenting with factors, which adversely influence postoperative pain, like long-lasting preoperative pain and opioid use (∼28% of the patients filled an opioid prescription 1 month before their surgery).230 However, studies evaluating analgesic interventions in this challenging group with chronic pain states, chronic opioid use, and psychiatric disorders are lacking.225,231 It is possible that analgesic interventions 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 in situations where the currently recommended interventions are not possible. Also, studies assessing the effects of analgesic interventions on functional outcomes, which is mandatory for rehabilitation, hospital length of stay, persistent postoperative pain and patient-related outcomes, are lacking. Although enhanced recovery pathways are increasingly implemented, none of the included studies reported use of such protocols,232 and there are no high-quality studies to assess the relative importance of the different analgesic techniques to facilitate an outpatient TKA facility. Recent reviews on the effect of peripheral nerve blocks on postoperative outcomes in TKA have supported their use,233 but it is noteworthy that this evidence is not built on studies with a short 1 to 2 days or an outpatient TKA facility, thereby limiting conclusions for current practice in many places.
The present review identified an optimal analgesic regimen for unilateral, primary TKA (Table 1). Analgesic interventions that could not be recommended were also identified (Table 2). Future well designed studies should evaluate the analgesic interventions in comparison with the use of co-analgesics (paracetamol, NSAIDs, local infiltration analgesia and glucocorticoid) instead of being placebo-controlled studies.14,234 Furthermore, these studies should focus on enhanced recovery programs232 with regards to early ambulation and patient-related outcomes. Also, studies assessing analgesic techniques in specific challenging patient groups are urgently needed.
Table 1 -
Overall recommendations for pain management following primary total knee arthroplasty
|Preoperative and intra-operative
| Paracetamol and nonsteroidal anti-inflammatory drugs or cyclo-oxygenase-2 specific inhibitors, administered either preoperatively or intra-operatively
| Single shot adductor canal block administered preoperatively and peri-articular local infiltration analgesia administered intra-operatively. Combination of these two techniques is preferred
| Dexamethasone (≥10 mg, i.v.) administered intra-operatively
| Intrathecal morphine (100 μg) may only be considered only in hospitalised patients when surgery is performed under spinal anaesthesia and in the rare situation wherein both adductor canal block and local infiltration analgesia are not possible
| Paracetamol and nonsteroidal anti-inflammatory drug or cyclo-oxygenase-2 specific inhibitors
| Opioids should be reserved as rescue analgesics
Table 2 -
Analgesic interventions that are not recommended for pain management following primary total knee arthroplasty
||Reason for not recommending
||Minimal analgesic and opioid-sparing effects and concerns of potential adverse effects, particularly when combined with postoperative opioids, which are typically high for total knee arthroplasty
||Potential adverse effects precluding rapid recovery
|Femoral nerve block
||Negative impact on functional recovery
|Sciatic nerve block
||Negative impact on functional recovery
Acknowledgements relating to this article
Assistance with the article: the authors thank Mrs Annett Finken for her help formatting the manuscript.
Financial support and sponsorship: PROSPECT is supported by an unrestricted grant from the European Society of Regional Anaesthesia and Pain Therapy (ESRA). In the past, PROSPECT has received unrestricted grants from Pfizer Inc. New York, New York, USA and Grunenthal, Aachen, Germany.
Conflicts of interest: GJ has received honoraria from Baxter International Inc and Pacira Bioscience Inc. FB has received honoraria from Pfizer, The Medicine Company, Abbott France and Nordic Pharma France. SS's institution has received research and travel funding and speaking and consulting honoraria from bioCSL, Eli Lilly, Indivior, iX Biopharma and Pfizer. MVdV received honoraria from Sintetica, Grunenthal, Vifor Pharma, MSD, Nordic Pharma, CLS Behring, Janssen Pharmaceuticals, Heron Therapeutics and Aquettant.
PROSPECT Working Group: G.P. Joshi, E. Pogatzki-Zahn, M. Van de Velde, M-P. Bonnet, H. Kehlet, F. Bonnet, N. Rawal, A. Delbos, P. Lavand’homme, H. Beloeil, J. Raeder, A. Sauter, E. Albrecht, P. Lirk, S. Freys, D. Lobo.
1. Price AJ, Alvand A, Troelsen A, et al. Knee replacement. Lancet
2. Karlsen AP, Wetterslev M, Hansen SE, et al. Postoperative pain treatment after total knee arthroplasty: a systematic review. PloS One
3. Dong P, Tang X, Cheng R, et al. Comparison of the efficacy of different analgesia treatments for total knee arthroplasty: a network meta-analysis. Clin J Pain
4. Soffin EM, Wu CL. Regional and multimodal analgesia to reduce opioid use after total joint arthroplasty: a narrative review. HSS J
5. Terkawi AS, Mavridis D, Sessler DI, et al. Pain management modalities after total knee arthroplasty: a network meta-analysis of 170 randomized controlled trials. Anesthesiology
6. Soffin EM, Gibbons MM, Ko CY, et al. Evidence review conducted for the agency for healthcare research and quality safety program for improving surgical care and recovery: focus on anesthesiology for total knee arthroplasty. Anesth Analg
7. Kopp SL, Borglum J, Buvanendran A, et al. Anesthesia and analgesia practice pathway options for total knee arthroplasty: an evidence-based review by the American and European Societies of Regional Anesthesia and Pain Medicine. Reg Anesth Pain Med
8. Soffin EM, Memtsoudis SG. Anesthesia and analgesia for total knee arthroplasty. Minerva Anestesiol
9. Sah AP, Liang K, Sclafani JA. Optimal multimodal analgesia treatment recommendations for total joint arthroplasty: a critical analysis review. JBJS Rev
10. Grosu I, Lavand’homme P, Thienpont E. Pain after knee arthroplasty: an unresolved issue. Knee Surg Sports Traumatol Arthrosc
11. Wylde V, Beswick A, Bruce J, et al. Chronic pain after total knee arthroplasty. EFORT Open Rev
12. Joshi GP, Kehlet H. PROSPECT Working Group. Guidelines for perioperative pain management: need for re-evaluation. Br J Anaesth
13. Joshi GP, Van de Velde M, Kehlet H. PROSPECT Working Group Collaborators. Development of evidence-based recommendations for procedure-specific pain management: PROSPECT methodology. Anaesthesia
14. Kehlet H, Joshi GP. The systematic review/meta-analysis epidemic: a tale of glucocorticoid therapy in total knee arthroplasty. Anaesthesia
15. Joshi GP, Kehlet H. Meta-analyses of gabapentinoids for pain management after knee arthroplasty: a caveat emptor? A narrative review. Acta Anaesthesiol Scand
16. Benzon HT, Joshi GP, Gan TJ, et al. Development, reporting, and evaluation of clinical practice guidelines. Anesth Analg
17. Tugwell P, Knottnerus JA. Adolopment - a new term added to the Clinical Epidemiology Lexicon. J Clin Epidemiol
18. NICE. Evidence review for anaesthesia for knee replacement. Nice guideline NG 1517. June 2020. National Institute for Health and Care Excellence. 2020.
19. Guo H, Wang C, He Y. A meta-analysis evaluates the efficacy of intravenous acetaminophen for pain management in knee or hip arthroplasty. J Orthop Sci
20. Liang L, Cai Y, Li A, et al. The efficiency of intravenous acetaminophen for pain control following total knee and hip arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore)
21. Shi SB, Wang XB, Song JM, et al. Efficacy of intravenous acetaminophen in multimodal management for pain relief following total knee arthroplasty: a meta-analysis. J Orthop Surg Res
22. Sun L, Zhu X, Zou J, et al. Comparison of intravenous and oral acetaminophen for pain control after total knee and hip arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore)
23. Yang L, Du S, Sun Y. Intravenous acetaminophen as an adjunct to multimodal analgesia after total knee and hip arthroplasty: a systematic review and meta-analysis. Int J Surg
24. Fillingham YA, Hannon CP, Erens GA, et al. The efficacy and safety of acetaminophen in total joint arthroplasty: systematic review and direct meta-analysis. J Arthroplasty
25. O’Neal JB, Freiberg AA, Yelle MD, et al. Intravenous vs oral acetaminophen as an adjunct to multimodal analgesia after total knee arthroplasty: a prospective, randomized, double-blind clinical trial. J Arthroplasty
26. Murata-Ooiwa M, Tsukada S, Wakui M. Intravenous acetaminophen in multimodal pain management for patients undergoing total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. J Arthroplasty
27. Du X, Gu J. The efficacy and safety of parecoxib for reducing pain and opioid consumption following total knee arthroplasty: a meta-analysis of randomized controlled trials. Int J Surg
28. Fillingham YA, Hannon CP, Roberts KC, et al. The efficacy and safety of nonsteroidal anti-inflammatory drugs in total joint arthroplasty: systematic review and direct meta-analysis. J Arthroplasty
29. Zhu Y, Wang S, Wu H, et al. Effect of perioperative parecoxib on postoperative pain and local inflammation factors PGE2 and IL-6 for total knee arthroplasty: a randomized, double-blind, placebo-controlled study. Eur J Orthop Surg Traumatol
30. Essex MN, Choi HY, Bhadra Brown P, et al. A randomized study of the efficacy and safety of parecoxib for the treatment of pain following total knee arthroplasty in Korean patients. J Pain Res
31. Gong L, Dong JY, Li ZR. Effects of combined application of muscle relaxants and celecoxib administration after total knee arthroplasty (TKA) on early recovery: a randomized, double-blind, controlled study. J Arthroplasty
32. Munteanu AM, Cionac Florescu S, Anastase DM, et al. Is there any analgesic benefit from preoperative vs. postoperative administration of etoricoxib in total knee arthroplasty under spinal anaesthesia?: a randomised double-blind placebo-controlled trial. Eur J Anaesthesiol
33. Reynolds LW, Hoo RK, Brill RJ, et al. The COX-2 specific inhibitor, valdecoxib, is an effective, opioid-sparing analgesic in patients undergoing total knee arthroplasty. J Pain Symptom Manage
34. Meunier A, Lisander B, Good L. Effects of celecoxib on blood loss, pain, and recovery of function after total knee replacement: a randomized placebo-controlled trial. Acta Orthop
35. Bian YY, Wang LC, Qian WW, et al. Role of parecoxib sodium in the multimodal analgesia after total knee arthroplasty: a randomized double-blinded controlled trial. Orthop Surg
36. Koh IJ, Chang CB, Lee JH, et al. Preemptive low-dose dexamethasone reduces postoperative emesis and pain after TKA: a randomized controlled study. Clin Orthop Rel Res
37. Xu H, Zhang S, Xie J, et al. Multiple doses of perioperative dexamethasone further improve clinical outcomes after total knee arthroplasty: a prospective, randomized, controlled study. J Arthroplasty
38. Lunn TH, Kristensen BB, Andersen LO, et al. Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial. Br J Anaesth
39. Xu B, Ma J, Huang Q, et al. Two doses of low-dose perioperative dexamethasone improve the clinical outcome after total knee arthroplasty: a randomized controlled study. Knee Surg Sports Traumatol Arthrosc
40. Li D, Zhao J, Yang Z, et al. Multiple low doses of intravenous corticosteroids to improve early rehabilitation in total knee arthroplasty: a randomized clinical trial. J Knee Surg
41. Dissanayake R, Du HN, Robertson IK, et al. Does dexamethasone reduce hospital readiness for discharge, pain, nausea, and early patient satisfaction in hip and knee arthroplasty? A randomized, controlled trial. J Arthroplasty
42. Jorgensen CC, Pitter FT, Kehlet H. Lundbeck Foundation Center for Fast-track H, Knee Replacement Collaborative Group. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement. Br J Anaesth
43. Feeley AA, Feeley TB, Feeley IH, et al. Postoperative infection risk in total joint arthroplasty after perioperative IV corticosteroid administration: a systematic review and meta-analysis of comparative studies. J Arthroplasty
44. Kang J, Zhao Z, Lv J, et al. The efficacy of perioperative gabapentin for the treatment of postoperative pain following total knee and hip arthroplasty: a meta-analysis. J Orthop Surg Res
45. Han C, Li XD, Jiang HQ, et al. The use of gabapentin in the management of postoperative pain after total knee arthroplasty: a PRISMA-compliant meta-analysis of randomized controlled trials. Medicine (Baltimore)
46. Zhai L, Song Z, Liu K. The effect of gabapentin on acute postoperative pain in patients undergoing total knee arthroplasty: a meta-analysis. Medicine (Baltimore)
47. Hamilton TW, Strickland LH, Pandit HG. A meta-analysis on the use of gabapentinoids for the treatment of acute postoperative pain following total knee arthroplasty. J Bone Joint Surg Am
48. Clarke H, Pereira S, Kennedy D, et al. Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty. Pain Res Manag
49. Clarke HA, Katz J, McCartney CJ, et al. Perioperative gabapentin reduces 24 h opioid consumption and improves in-hospital rehabilitation but not postdischarge outcomes after total knee arthroplasty with peripheral nerve block. Br J Anaesth
50. Paul JE, Nantha-Aree M, Buckley N, et al. Gabapentin does not improve multimodal analgesia outcomes for total knee arthroplasty: a randomized controlled trial. Can J Anaesth
51. Lunn TH, Husted H, Laursen MB, et al. Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty: a randomized, double-blind, placebo-controlled dose-finding study. Pain
52. Dong J, Li W, Wang Y. The effect of pregabalin on acute postoperative pain in patients undergoing total knee arthroplasty: a meta-analysis. Int J Surg
53. Han C, Kuang MJ, Ma JX, et al. Is pregabalin effective and safe in total knee arthroplasty? A PRISMA-compliant meta-analysis of randomized-controlled trials. Medicine (Baltimore)
54. Li F, Ma J, Kuang M, et al. The efficacy of pregabalin for the management of postoperative pain in primary total knee and hip arthroplasty: a meta-analysis. J Orthop Surg Res
55. Buvanendran A, Kroin JS, Della Valle CJ, et al. Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg
56. Jain P, Jolly A, Bholla V, et al. Evaluation of efficacy of oral pregabalin in reducing postoperative pain in patients undergoing total knee arthroplasty. Ind J Orthop
57. Lee JK, Chung KS, Choi CH. The effect of a single dose of preemptive pregabalin administered with COX-2 inhibitor: a trial in total knee arthroplasty. J Arthroplasty
58. Singla NK, Chelly JE, Lionberger DR, et al. Pregabalin for the treatment of postoperative pain: results from three controlled trials using different surgical models. J Pain Res
59. Yadeau JT, Paroli L, Kahn RL, et al. Addition of pregabalin to multimodal analgesic therapy following ankle surgery: a randomized double-blind, placebo-controlled trial. Reg Anesth Pain Med
60. Yik JH, Tham WYW, Tay KH, et al. Perioperative pregabalin does not reduce opioid requirements in total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc
61. Li Z, Chen Y. Ketamine reduces pain and opioid consumption after total knee arthroplasty: a meta-analysis of randomized controlled studies. Int J Surg
62. Wang P, Yang Z, Shan S, et al. Analgesic effect of perioperative ketamine for total hip arthroplasties and total knee arthroplasties: a PRISMA-compliant meta-analysis. Medicine (Baltimore)
63. Xu B, Wang Y, Zeng C, et al. Analgesic efficacy and safety of ketamine after total knee or hip arthroplasty: a meta-analysis of randomised placebo-controlled studies. BMJ Open
64. Aveline C, Gautier JF, Vautier P, et al. Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam. Eur J Pain
65. Cengiz P, Gokcinar D, Karabeyoglu I, et al. Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial. J Coll Physicians Surg Pak
66. Tan TL, Longenecker AS, Rhee JH, et al. Intraoperative ketamine in total knee arthroplasty does not decrease pain and narcotic consumption: a prospective randomized controlled trial. J Arthroplasty
67. Adam F, Chauvin M, Du Manoir B, et al. Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty. Anesth Analg
68. Perrin SB, Purcell AN. Intraoperative ketamine may influence persistent pain following knee arthroplasty under combined general and spinal anaesthesia: a pilot study. Anaesth Intensive Care
69. Aveline C, Roux AL, Hetet HL, et al. Pain and recovery after total knee arthroplasty: a 12-month follow-up after a prospective randomized study evaluating Nefopam and Ketamine for early rehabilitation. Clin J Pain
70. Yang Q, Ren Y, Feng B, et al. Pain relieving effect of dexmedetomidine in patients undergoing total knee or hip arthroplasty: A meta-analysis. Medicine (Baltimore)
71. Chan IA, Maslany JG, Gorman KJ, et al. Dexmedetomidine during total knee arthroplasty performed under spinal anesthesia decreases opioid use: a randomized-controlled trial. Can J Anaesth
72. Shin HJ, Do SH, Lee JS, et al. Comparison of intraoperative sedation with dexmedetomidine versus propofol on acute postoperative pain in total knee arthroplasty under spinal anesthesia: a randomized trial. Anesth Analg
73. Cole PJ, Craske DA, Wheatley RG. Efficacy and respiratory effects of low-dose spinal morphine for postoperative analgesia following knee arthroplasty. Br J Anaesth
74. Tan PH, Chia YY, Lo Y, et al. Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia after total knee replacement surgery. Can J Anaesth
75. Park CK, Cho CK, Lee JH, et al. Optimizing the dose of intrathecal morphine when combined with continuous 3-in-1 nerve block after total knee replacement. Korean J Anesthesiol
76. Lauretti GR, Righeti CC, Mattos AL. Intrathecal ketorolac enhances intrathecal morphine analgesia following total knee arthroplasty. J Anaesthesiol Clin Pharmacol
77. Kunopart M, Chanthong P, Thongpolswat N, et al. Effects of single shot femoral nerve block combined with intrathecal morphine for postoperative analgesia: a randomized, controlled, dose-ranging study after total knee arthroplasty. J Med Assoc Thai
78. Olive DJ, Barrington MJ, Simone SA, et al. A randomised controlled trial comparing three analgesia regimens following total knee joint replacement: continuous femoral nerve block, intrathecal morphine or both. Anaesth Intensive Care
79. Sundarathiti P, Thammasakulsiri J, Supboon S, et al. Comparison of continuous femoral nerve block (CFNB/SA) and continuous femoral nerve block with mini-dose spinal morphine (CFNB/SAMO) for postoperative analgesia after total knee arthroplasty (TKA): a randomized controlled study. BMC Anesthesiol
80. Barrington JW, Emerson RH, Lovald ST, et al. No difference in early analgesia between liposomal bupivacaine injection and intrathecal morphine after TKA. Clin Orthopaed Relat Res
81. Biswas A, Perlas A, Ghosh M, et al. Relative contributions of adductor canal block and intrathecal morphine to analgesia and functional recovery after total knee arthroplasty: a randomized controlled trial. Reg Anesth Pain Med
82. Kaczocha M, Azim S, Nicholson J, et al. Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial. BMC Anesthesiol
83. Miyamoto S, Sugita T, Aizawa T, et al. The effect of morphine added to periarticular multimodal drug injection or spinal anesthesia on pain management and functional recovery after total knee arthroplasty. J Orthop Sci
84. Schumer G, Mann JW 3rd, Stover MD, et al. Liposomal bupivacaine utilization in total knee replacement does not decrease length of hospital stay. J Knee Surg
85. Tang Y, Tang X, Wei Q, et al. Intrathecal morphine versus femoral nerve block for pain control after total knee arthroplasty: a meta-analysis. J Orthop Surg Res
86. Li XM, Huang CM, Zhong CF. Intrathecal morphine verse femoral nerve block for pain control in total knee arthroplasty: a meta-analysis from randomized control trials. Int J Surg
87. Qi BC, Yu J, Qiao WS. Comparison of intrathecal morphine versus local infiltration analgesia for pain control in total knee and hip arthroplasty: a meta-analysis. Medicine (Baltimore)
88. Sites BD, Beach M, Gallagher JD, et al. A single injection ultrasound-assisted femoral nerve block provides side effect-sparing analgesia when compared with intrathecal morphine in patients undergoing total knee arthroplasty. Anesth Analg
89. Frassanito L, Vergari A, Zanghi F, et al. Postoperative analgesia following total knee arthroplasty: comparison of low-dose intrathecal morphine and single-shot ultrasound-guided femoral nerve block: a randomized, single blinded, controlled study. Eur Rev Med Pharmacol Sci
90. Tarkkila P, Tuominen M, Huhtala J, et al. Comparison of intrathecal morphine and continuous femoral 3-in-1 block for pain after major knee surgery under spinal anaesthesia. Eur J Anaesthesiol
91. Essving P, Axelsson K, Aberg E, et al. Local infiltration analgesia versus intrathecal morphine for postoperative pain management after total knee arthroplasty: a randomized controlled trial. Anesth Analg
92. Tammachote N, Kanitnate S, Manuwong S, et al. Is pain after TKA better with periarticular injection or intrathecal morphine? Clin Orthopaed Relat Res
93. Zhang W, Zhang Y, Hui H. Intrathecal morphine versus local infiltration analgesia for pain control in total knee arthroplasty patients: a randomized clinical trial. Jiangsu Med J
94. McCarthy D, McNamara J, Galbraith J, et al. A comparison of the analgesic efficacy of local infiltration analgesia vs. intrathecal morphine after total knee replacement: a randomised controlled trial. Eur J Anaesthesiol
95. Gerrard AD, Brooks B, Asaad P, et al. Meta-analysis of epidural analgesia versus peripheral nerve blockade after total knee joint replacement. Eur J Orthop Surg Traumatol
96. Li C, Qu J, Pan S, et al. Local infiltration anesthesia versus epidural analgesia for postoperative pain control in total knee arthroplasty: a systematic review and meta-analysis. J Orthop Surg Res
97. Singelyn FJ, Deyaert M, Joris D, et al. Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty. Anesth Analg
98. Capdevila X, Barthelet Y, Biboulet P, et al. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology
99. Adams HA, Saatweber P, Schmitz CS, et al. Postoperative pain management in orthopaedic patients: no differences in pain score, but improved stress control by epidural anaesthesia. Eur J Anaesthesiol
100. Davies AF, Segar EP, Murdoch J, et al. Epidural infusion or combined femoral and sciatic nerve blocks as perioperative analgesia for knee arthroplasty. Br J Anaesth
101. Barrington MJ, Olive D, Low K, et al. Continuous femoral nerve blockade or epidural analgesia after total knee replacement: a prospective randomized controlled trial. Anesth Analg
102. Zaric D, Boysen K, Christiansen C, et al. A comparison of epidural analgesia with combined continuous femoral-sciatic nerve blocks after total knee replacement. Anesth Analg
103. Campbell A, McCormick M, McKinlay K, et al. Epidural vs. lumbar plexus infusions following total knee arthroplasty: randomized controlled trial. Eur J Anaesthesiol
104. Sakai N, Inoue T, Kunugiza Y, et al. Continuous femoral versus epidural block for attainment of 120 degrees knee flexion after total knee arthroplasty: a randomized controlled trial. J Arthroplasty
105. Klasen JA, Opitz SA, Melzer C, et al. Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty. Acta Anaesthesiol Scand
106. Andersen KV, Bak M, Christensen BV, et al. A randomized, controlled trial comparing local infiltration analgesia with epidural infusion for total knee arthroplasty. Acta Orthop
107. Spreng UJ, Dahl V, Hjall A, et al. High-volume local infiltration analgesia combined with intravenous or local ketorolac+morphine compared with epidural analgesia after total knee arthroplasty. Br J Anaesth
108. Binici Bedir E, Kurtulmus T, Basyigit S, et al. A comparison of epidural analgesia and local infiltration analgesia methods in pain control following total knee arthroplasty. Acta Orthop Traumatol Turc
109. Tsukada S, Wakui M, Hoshino A. Postoperative epidural analgesia compared with intraoperative periarticular injection for pain control following total knee arthroplasty under spinal anesthesia: a randomized controlled trial. J Bone Joint Surg Am
110. Kasture S, Saraf H. Epidural versus intra-articular infusion analgesia following total knee replacement. J Orthop Surg (Hong Kong)
111. Dong CC, Dong SL, He FC. Comparison of adductor canal block and femoral nerve block for postoperative pain in total knee arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore)
112. Gao F, Ma J, Sun W, et al. Adductor canal block versus femoral nerve block for analgesia after total knee arthroplasty: a systematic review and meta-analysis. Clin J Pain
113. Kuang MJ, Ma JX, Fu L, et al. Is adductor canal block better than femoral nerve block in primary total knee arthroplasty? A GRADE analysis of the evidence through a systematic review and meta-analysis. J Arthroplasty
114. Kuang MJ, Xu LY, Ma JX, et al. Adductor canal block versus continuous femoral nerve block in primary total knee arthroplasty: a meta-analysis. Int J Surg
115. Li D, Yang Z, Xie X, et al. Adductor canal block provides better performance after total knee arthroplasty compared with femoral nerve block: a systematic review and meta-analysis. Int Orthop
116. Wang D, Yang Y, Li Q, et al. Adductor canal block versus femoral nerve block for total knee arthroplasty: a meta-analysis of randomized controlled trials. Sci Rep
117. Zhang Z, Wang Y, Liu Y. Effectiveness of continuous adductor canal block versus continuous femoral nerve block in patients with total knee arthroplasty: a PRISMA guided systematic review and meta-analysis. Medicine (Baltimore)
118. Zhao XQ, Jiang N, Yuan FF, et al. The comparison of adductor canal block with femoral nerve block following total knee arthroplasty: a systematic review with meta-analysis. J Anesth
119. Mei S, Jin S, Chen Z, et al. Analgesia for total knee arthroplasty: a meta-analysis comparing local infiltration and femoral nerve block. Clinics (Sao Paulo)
120. Yun XD, Yin XL, Jiang J, et al. Local infiltration analgesia versus femoral nerve block in total knee arthroplasty: a meta-analysis. Orthop Traumatol Surg Res
121. Zhang Z, Yang Q, Xin W, et al. Comparison of local infiltration analgesia and sciatic nerve block as an adjunct to femoral nerve block for pain control after total knee arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore)
122. Zhang LK, Ma JX, Kuang MJ, et al. Comparison of periarticular local infiltration analgesia with femoral nerve block for total knee arthroplasty: a meta-analysis of randomized controlled trials. J Arthroplasty
123. Albrecht E, Guyen O, Jacot-Guillarmod A, et al. The analgesic efficacy of local infiltration analgesia vs femoral nerve block after total knee arthroplasty: a systematic review and meta-analysis. Br J Anaesth
124. Memtsoudis SG, Danninger T, Rasul R, et al. Inpatient falls after total knee arthroplasty: the role of anesthesia type and peripheral nerve blocks. Anesthesiology
125. Elkassabany NM, Antosh S, Ahmed M, et al. The risk of falls after total knee arthroplasty with the use of a femoral nerve block versus an adductor canal block: a double-blinded randomized controlled study. Anesth Analg
126. Abdallah FW, Madjdpour C, Brull R. Is sciatic nerve block advantageous when combined with femoral nerve block for postoperative analgesia following total knee arthroplasty? A meta-analysis. Can J Anaesth
127. Grape S, Kirkham KR, Baeriswyl M, Albrecht E. The analgesic efficacy of sciatic nerve block in addition to femoral nerve block in patients undergoing total knee arthroplasty: a systematic review and meta-analysis. Anaesthesia
128. Zorrilla-Vaca A, Li J. The role of sciatic nerve block to complement femoral nerve block in total knee arthroplasty: a meta-analysis of randomized controlled trials. J Anesth
129. Li J, Deng X, Jiang T. Combined femoral and sciatic nerve block versus femoral and local infiltration anesthesia for pain control after total knee arthroplasty: a meta-analysis of randomized controlled trials. J Orthop Surg Res
130. Ma LP, Qi YM, Zhao DX. Comparison of local infiltration analgesia and sciatic nerve block for pain control after total knee arthroplasty: a systematic review and meta-analysis. J Orthop Surg Res
131. Safa B, Gollish J, Haslam L, et al. Comparing the effects of single shot sciatic nerve block versus posterior capsule local anesthetic infiltration on analgesia and functional outcome after total knee arthroplasty: a prospective, randomized, double-blinded, controlled trial. J Arthroplasty
132. Tanikawa H, Sato T, Nagafuchi M, et al. Comparison of local infiltration of analgesia and sciatic nerve block in addition to femoral nerve block for total knee arthroplasty. J Arthroplasty
133. Gi E, Yamauchi M, Yamakage M, et al. Effects of local infiltration analgesia for posterior knee pain after total knee arthroplasty: comparison with sciatic nerve block. J Anesth
134. Mahadevan D, Walter RP, Minto G, et al. Combined femoral and sciatic nerve block vs combined femoral and periarticular infiltration in total knee arthroplasty: a randomized controlled trial. J Arthroplasty
135. Uesugi K, Kitano N, Kikuchi T, et al. Comparison of peripheral nerve block with periarticular injection analgesia after total knee arthroplasty: a randomized, controlled study. Knee
136. Nagafuchi M, Sato T, Sakuma T, et al. Femoral nerve block-sciatic nerve block vs. femoral nerve block-local infiltration analgesia for total knee arthroplasty: a randomized controlled trial. BMC Anesthesiol
137. Spangehl MJ, Clarke HD, Hentz JG, et al. The Chitranjan Ranawat Award: periarticular injections and femoral & sciatic blocks provide similar pain relief after TKA: a randomized clinical trial. Clin Orthopaed Relat Res
138. Li Y, Li A, Zhang Y. The efficacy of combined adductor canal block with local infiltration analgesia for pain control after total knee arthroplasty: a meta-analysis. Medicine (Baltimore)
139. Lv J, Huang C, Wang Z, et al. Adductor canal block combined with local infiltration analgesia versus isolated adductor canal block in reducing pain and opioid consumption after total knee arthroplasty: a systematic review and meta-analysis. J Int Med Res
140. Zhao Y, Huang Z, Ma W. Comparison of adductor canal block with local infiltration analgesia in primary total knee arthroplasty: a meta-analysis of randomized controlled trials. Int J Surg
141. Zuo W, Guo W, Ma J, et al. Dose adductor canal block combined with local infiltration analgesia has a synergistic effect than adductor canal block alone in total knee arthroplasty: a meta-analysis and systematic review. J Orthop Surg Res
142. Sardana V, Burzynski JM, Scuderi GR. Adductor canal block or local infiltrate analgesia for pain control after total knee arthroplasty? a systematic review and meta-analysis of randomized controlled trials. J Arthroplasty
143. Hussain N, Brull R, Sheehy B, et al. Does the addition of iPACK to adductor canal block in the presence or absence of periarticular local anesthetic infiltration improve analgesic and functional outcomes following total knee arthroplasty? A systematic review and meta-analysis. Reg Anesth Pain Med
144. Mingdeng X, Yuzhang A, Xiaoxiao X, et al. Combined application of adductor canal block and local infiltration anesthesia in primary total knee arthroplasty: an updated meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg
2021; [Epub ahead of print].
145. Fan J, Li AJ, Zi CN. Combined adductor canal block with local infiltrative analgesia for pain management in total knee arthroplasty: a meta-analysis. Int J Surg
146. Fan L, Zhu C, Zan P, et al. The comparison of local infiltration analgesia with peripheral nerve block following total knee arthroplasty (TKA): a systematic review with meta-analysis. J Arthroplasty
147. Zhang LK, Li Q, Zhu FB, et al. Comparison of adductor canal block with periarticular infiltration analgesia in total knee arthroplasty: a meta-analysis of randomized controlled trials. Medicine (Baltimore)
148. Yu R, Wang H, Zhuo Y, et al. Continuous adductor canal block provides better performance after total knee arthroplasty compared with the single-shot adductor canal block?: An updated meta-analysis of randomized controlled trials. Medicine (Baltimore)
149. Sun C, Zhang X, Song F, et al. Is continuous catheter adductor canal block better than single-shot canal adductor canal block in primary total knee arthroplasty?: a GRADE analysis of the evidence through a systematic review and meta-analysis. Medicine (Baltimore)
150. Wang C, Chen Z, Ma X. Continuous adductor canal block is a better choice compared to single shot after primary total knee arthroplasty: a meta-analysis of randomized controlled trials. Int J Surg
151. Zhang LK, Zhang BY, Quan RF, et al. Single shot versus continuous technique adductor canal block for analgesia following total knee arthroplasty: a PRISMA-compliant meta-analysis. Medicine (Baltimore)
152. Schnabel A, Reichl SU, Weibel S, et al. Adductor canal blocks for postoperative pain treatment in adults undergoing knee surgery. Cochrane Database Syst Rev
153. Jenstrup MT, Jæger P, Lund J, et al. Effects of adductor-canal-blockade on pain and ambulation after total knee arthroplasty: a randomized study. Acta Anaesthesiol Scand
154. Jaeger P, Grevstad U, Henningsen MH, et al. Effect of adductor-canal-blockade on established, severe postoperative pain after total knee arthroplasty: a randomised study. Acta Anaesthesiol Scand
155. Grevstad U, Mathiesen O, Lind T, et al. Effect of adductor canal block on pain in patients with severe pain after total knee arthroplasty: a randomized study with individual patient analysis. Br J Anaesth
156. Hanson NA, Allen CJ, Hostetter LS, et al. Continuous ultrasound-guided adductor canal block for total knee arthroplasty: a randomized, double-blind trial. Anesth Analg
157. Zhang W, Hu Y, Tao Y, et al. Ultrasound-guided continuous adductor canal block for analgesia after total knee replacement. Chin Med J (Engl)
158. Kim DH, Lin Y, Goytizolo EA, et al. Adductor canal block versus femoral nerve block for total knee arthroplasty: a prospective, randomized, controlled trial. Anesthesiology
159. Grevstad U, Mathiesen O, Valentiner LS, et al. Effect of adductor canal block versus femoral nerve block on quadriceps strength, mobilization, and pain after total knee arthroplasty: a randomized, blinded study. Reg Anesth Pain Med
160. Memtsoudis SG, Yoo D, Stundner O, et al. Subsartorial adductor canal vs femoral nerve block for analgesia after total knee replacement. Int Orthop
161. Macrinici GI, Murphy C, Christman L, et al. Prospective, double-blind, randomized study to evaluate single-injection adductor canal nerve block versus femoral nerve block: postoperative functional outcomes after total knee arthroplasty. Reg Anesth Pain Med
162. Shah NA, Jain NP, Panchal KA. Adductor canal blockade following total knee arthroplasty-continuous or single shot technique? role in postoperative analgesia, ambulation ability and early functional recovery: a randomized controlled trial. J Arthroplasty
163. Turner JD, Dobson SW, Henshaw DS, et al. Single-injection adductor canal block with multiple adjuvants provides equivalent analgesia when compared with continuous adductor canal blockade for primary total knee arthroplasty: a double-blinded, randomized, controlled, equivalency trial. J Arthroplasty
164. Lee S, Rooban N, Vaghadia H, et al. A randomized non-inferiority trial of adductor canal block for analgesia after total knee arthroplasty: single injection versus catheter technique. J Arthroplasty
165. Elkassabany NM, Cai LF, Badiola I, et al. A prospective randomized open-label study of single injection versus continuous adductor canal block for postoperative analgesia after total knee arthroplasty. Bone Joint J
166. Zhang Y, Tan Z, Liao R, et al. The prolonged analgesic efficacy of an ultrasound-guided single-shot adductor canal block in patients undergoing total knee arthroplasty. Orthopedics
167. Lyngeraa TS, Jaeger P, Gottschau B, et al. Comparison of the analgesic effect of an adductor canal block using a new suture-method catheter vs. standard perineural catheter vs. single-injection: a randomised, blinded, controlled study. Anaesthesia
168. Canbek U, Akgun U, Aydogan NH, et al. Continuous adductor canal block following total knee arthroplasty provides a better analgesia compared to single shot: a prospective randomized controlled trial. Acta Orthop Traumatol Turc
169. Sawhney M, Mehdian H, Kashin B, et al. Pain after unilateral total knee arthroplasty: a prospective randomized controlled trial examining the analgesic effectiveness of a combined adductor canal peripheral nerve block with periarticular infiltration versus adductor canal nerve block alone versus periarticular infiltration alone. Anesth Analg
170. Grosso MJ, Murtaugh T, Lakra A, et al. Adductor canal block compared with periarticular bupivacaine injection for total knee arthroplasty: a prospective randomized trial. J Bone Joint Surg Am
171. Zhou M, Ding H, Ke J. Adductor canal block in combination with posterior capsular infiltration on the pain control after TKA. Ir J Med Sci
172. Kampitak W, Tanavalee A, Ngarmukos S, et al. Comparison of adductor canal block versus local infiltration analgesia on postoperative pain and functional outcome after total knee arthroplasty: a randomized controlled trial. Malays Orthop J
173. Tong QJ, Lim YC, Tham HM. Comparing adductor canal block with local infiltration analgesia in total knee arthroplasty: a prospective, blinded and randomized clinical trial. J Clin Anesth
174. Nader A, Kendall MC, Manning DW, et al. Single-dose adductor canal block with local infiltrative analgesia compared with local infiltrate analgesia after total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med
175. Cicekci F, Yildirim AO, Onal O, et al. Ultrasounds-guided adductor canal block using levobupivacaine versus periarticular levobupivacaine infiltration after total knee arthroplasty: a randomized clinical trial. Sao Paulo Med J
176. Goytizolo EA, Lin Y, Kim DH, et al. Addition of adductor canal block to periarticular injection for total knee replacement: a randomized trial. J Bone Joint Surg Am
177. Andersen HL, Gyrn J, Moller L, et al. Continuous saphenous nerve block as supplement to single-dose local infiltration analgesia for postoperative pain management after total knee arthroplasty. Reg Anesth Pain Med
178. Gudmundsdottir S, Franklin JL. Continuous adductor canal block added to local infiltration analgesia (LIA) after total knee arthroplasty has no additional benefits on pain and ambulation on postoperative day 1 and 2 compared with LIA alone. Acta Orthop
179. Andersen LO, Kehlet H. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty: a systematic review. Br J Anaesth
180. Xu CP, Li X, Wang ZZ, et al. Efficacy and safety of single-dose local infiltration of analgesia in total knee arthroplasty: a meta-analysis of randomized controlled trials. Knee
181. Seangleulur A, Vanasbodeekul P, Prapaitrakool S, et al. The efficacy of local infiltration analgesia in the early postoperative period after total knee arthroplasty: a systematic review and meta-analysis. Eur J Anaesthesiol
182. Fang R, Liu Z, Alijiang A, et al. Efficacy of intra-articular local anesthetics in total knee arthroplasty. Orthopedics
183. Zhang Z, Shen B. Effectiveness and weakness of local infiltration analgesia in total knee arthroplasty: a systematic review. J Int Med Res
184. Hussain N, Ferreri TG, Prusick PJ, et al. Adductor canal block versus femoral canal block for total knee arthroplasty: a meta-analysis: what does the evidence suggest? Reg Anesth Pain Med
185. Jiang X, Wang QQ, Wu CA, et al. Analgesic efficacy of adductor canal block in total knee arthroplasty: a meta-analysis and systematic review. Orthop Surg
186. Li D, Ma GG. Analgesic efficacy and quadriceps strength of adductor canal block versus femoral nerve block following total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc
187. Paul JE, Arya A, Hurlburt L, et al. Femoral nerve block improves analgesia outcomes after total knee arthroplasty: a meta-analysis of randomized controlled trials. Anesthesiology
188. Wang C, Cai XZ, Yan SG. Comparison of periarticular multimodal drug injection and femoral nerve block for postoperative pain management in total knee arthroplasty: a systematic review and meta-analysis. J Arthroplasty
189. Hu B, Lin T, Yan SG, et al. Local infiltration analgesia versus regional blockade for postoperative analgesia in total knee arthroplasty: a meta-analysis of randomized controlled trials. Pain Physician
190. Sun XL, Zhao ZH, Ma JX, et al. Continuous local infiltration analgesia for pain control after total knee arthroplasty: a meta-analysis of randomized controlled trials. Medicine (Baltimore)
191. Ma T, Liu Q, Zhou L, et al. Continuous nerve block versus single-shot nerve block for total knee arthroplasty: a meta-analysis from randomized controlled trials. Minerva Anestesiol
192. Wu ZQ, Min JK, Wang D. Liposomal bupivacaine for pain control after total knee arthroplasty: a meta-analysis. J Orthop Surg Res
193. Kuang MJ, Du Y, Ma JX, et al. The efficacy of liposomal bupivacaine using periarticular injection in total knee arthroplasty: a systematic review and meta-analysis. J Arthroplasty
194. Singh PM, Borle A, Trikha A, et al. Role of periarticular liposomal bupivacaine infiltration in patients undergoing total knee arthroplasty-a meta-analysis of comparative trials. J Arthroplasty
195. Wang X, Xiao L, Wang Z, et al. Comparison of peri-articular liposomal bupivacaine and standard bupivacaine for postsurgical analgesia in total knee arthroplasty: a systematic review and meta-analysis. Int J Surg
196. Liu Y, Zeng JF, Zeng Y, et al. Comprehensive comparison of liposomal bupivacaine with femoral nerve block for pain control following total knee arthroplasty: an updated systematic review and meta-analysis. Orthop Surg
197. Sun H, Huang Z, Zhang Z, et al. A meta-analysis comparing liposomal bupivacaine and traditional periarticular injection for pain control after total knee arthroplasty. J Knee Surg
198. Hamilton TW, Athanassoglou V, Mellon S, et al. Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev
199. Schroer WC, Diesfeld PJ, LeMarr AR, et al. Benefits of prolonged postoperative cyclooxygenase-2 inhibitor administration on total knee arthroplasty recovery: a double-blind, placebo-controlled study. J Arthroplasty
2011; 26: (6 Suppl): 2–7.
200. Memtsoudis SG, Poeran J, Zubizarreta N, et al. Do hospitals performing frequent neuraxial anesthesia for hip and knee replacements have better outcomes? Anesthesiology
201. Memtsoudis SG, Fiasconaro M, Soffin EM, et al. Enhanced recovery after surgery components and perioperative outcomes: a nationwide observational study. Br J Anaesth
202. Bongiovanni T, Lancaster E, Ledesma Y, et al. Systematic review and meta-analysis of the association between non-steroidal anti-inflammatory drugs and operative bleeding in the perioperative period. J Am Coll Surg
203. Martinez V, Beloeil H, Marret E, et al. Nonopioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials. Br J Anaesth
204. Ong CK, Seymour RA, Lirk P, et al. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg
205. De Oliveira GS Jr, Almeida MD, Benzon HT, et al. Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology
206. Tammachote N, Kanitnate S. Intravenous dexamethasone injection reduces pain from 12 to 21 hours after total knee arthroplasty: a double-blind, randomized, placebo-controlled trial. J Arthroplasty
207. Kharasch ED, Clark JD, Kheterpal S. Perioperative gabapentinoids: deflating the bubble. Anesthesiology
208. Verret M, Lauzier F, Zarychanski R, et al. Canadian Perioperative Anesthesia Clinical Trials (PACT) Group. Perioperative use of gabapentinoids for the management of postoperative acute pain: a systematic review and meta-analysis. Anesthesiology
209. Albrecht E, Bayon V, Hirotsu C, et al. Intrathecal morphine and sleep apnoea severity in patients undergoing hip arthroplasty: a randomised, controlled, triple-blinded trial. Br J Anaesth
210. Golaz R, Tangel VE, Lui B, et al. Postoperative outcomes and anesthesia type in total hip arthroplasty in patients with obstructive sleep apnea: a retrospective analysis of the State Inpatient Databases. J Clin Anesth
211. Joshi GP, Kehlet H. Functional recovery after knee arthroplasty with regional analgesia. Eur J Anaesthesiol
212. Rawal N. Current issues in postoperative pain management. Eur J Anaesthesiol
213. Wasserstein D, Farlinger C, Brull R, et al. Advanced age, obesity and continuous femoral nerve blockade are independent risk factors for inpatient falls after primary total knee arthroplasty. J Arthroplasty
214. Lund J, Jenstrup MT, Jaeger P, et al. Continuous adductor-canal-blockade for adjuvant postoperative analgesia after major knee surgery: preliminary results. Acta Anaesthesiol Scand
215. 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
216. Pinsornsak P, Nangnual S, Boontanapibul K. Multimodal infiltration of local anaesthetic in total knee arthroplasty; is posterior capsular infiltration worth the risk? a prospective, double-blind, randomised controlled trial. Bone Joint J
217. Kelley TC, Adams MJ, Mulliken BD, et al. Efficacy of multimodal perioperative analgesia protocol with periarticular medication injection in total knee arthroplasty: a randomized, double-blinded study. J Arthroplasty
218. Andersen KV, Nikolajsen L, Haraldsted V, et al. Local infiltration analgesia for total knee arthroplasty: should ketorolac be added? Br J Anaesth
219. Schotanus MGM, Bemelmans YFL, van der Kuy PHM, et al. No advantage of adrenaline in the local infiltration analgesia mixture during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc
220. Tran J, Schwarzkopf R. Local infiltration anesthesia with steroids in total knee arthroplasty: a systematic review of randomized control trials. J Orthop
221. Ilfeld BM, Eisenach JC, Gabriel RA. Clinical effectiveness of liposomal bupivacaine administered by infiltration or peripheral nerve block to treat postoperative pain. Anesthesiology
222. Hussain N, Brull R, Sheehy BT, et al. The mornings after-periarticular liposomal bupivacaine infiltration does not improve analgesic outcomes beyond 24 h following total knee arthroplasty: a systematic review and meta-analysis. Reg Anesth Pain Med
223. Gromov K, Grassin-Delyle S, Foss NB, et al. Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty. Br J Anaesth
224. Munirama S, McLeod G. 'Stratified’ approach to individualized anaesthetic care. Br J Anaesth
225. Pedersen C, Troensegaard H, Laigaard J, et al. Differences in patient characteristics and external validity of randomized clinical trials on pain management following total hip and knee arthroplasty: a systematic review. Reg Anesth Pain Med
226. Gilron I, Carr DB, Desjardins PJ, et al. Current methods and challenges for acute pain clinical trials. Pain Rep
227. Kampitak W, Tanavalee A, Ngarmukos S, et al. Motor-sparing effect of iPACK (interspace between the popliteal artery and capsule of the posterior knee) block versus tibial nerve block after total knee arthroplasty: a randomized controlled trial. Reg Anesth Pain Med
228. Kavolus JJ, Sia D, Potter HG, et al. Saphenous nerve block from within the knee is feasible for TKA: MRI and cadaveric study. Clin Orthopaed Relat Res
229. Karlsen AP, Mathiesen O, Dahl JB. Heterogenic control groups in randomized, controlled, analgesic trials of total hip and knee arthroplasty. Minerva Anestesiol
230. DeMik DE, Carender CN, Shamrock AG, et al. Opioid use after total knee arthroplasty: does tramadol have lower risk than traditional opioids? J Arthroplasty
231. Kehlet H, Memtsoudis SG. ERAS guidelines for hip and knee replacement - need for reanalysis of evidence and recommendations? Acta Orthop
232. Kehlet H. Enhanced postoperative recovery: good from afar, but far from good? Anaesthesia
2020; 75: (Suppl 1): e54–e61.
233. Memtsoudis SG, Cozowicz C, Bekeris J, et al. Peripheral nerve block anesthesia/analgesia for patients undergoing primary hip and knee arthroplasty: recommendations from the International Consensus on Anesthesia-Related Outcomes after Surgery (ICAROS) group based on a systematic review and meta-analysis of current literature. Reg Anesth Pain Med
234. Kehlet H, Joshi GP. Systematic reviews and meta-analyses of randomized controlled trials on perioperative outcomes: an urgent need for critical reappraisal. Anesth Analg