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Background Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. Methods The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. Findings Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12–38) in the paracetamol plus ibuprofen group, 20 mg (12–32) in the paracetamol plus dexamethasone group, 16 mg (10–30) in the ibuprofen plus dexamethasone group, and 15 m, Background: Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. Methods: The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. Findings: Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12–38) in the paracetamol plus ibuprofen group, 20 mg (12–32) in the paracetamol plus dexamethasone group, 16 mg (10–30) in the ibuprofen plus dexamethasone group, and 15 mg (8–26) in the paraceta

Background Morphine-sparing effects are often used to evaluate non-opioid analgesic interventions. The exact effect that would warrant the implementation of these interventions in clinical practice (a minimally important difference) remains unclear. We aimed to determine this with anchor-based methods. Methods This was a post hoc analysis of three studies investigating pain management after hip or knee arthroplasty (PANSAID [NCT02571361], DEX-2-TKA [NCT03506789] and Pain Map [NCT02340052]). The overall population was median aged 70, median ASA 2, 54% female. We examined the correlation between 0 and 24 h postoperative iv morphine equivalent consumption and the severity of nausea, vomiting, sedation and dizziness. The anchor was different severity degrees of these opioid-related adverse events. The primary outcome was the difference in morphine consumption between patients experiencing no versus only mild events. Secondary outcomes included the difference in morphine consumption between patients with mild versus moderate and moderate versus severe events. We used Hodges–Lehmann median differences, exact Wilcoxon–Mann–Whitney tests and quantile regression. Results The difference in iv morphine consumption was 6 mg (95% confidence interval: 4–8) between patients with no versus only mild events, 5 mg (2–8) between patients with mild versus moderate events and 0 mg (−4 to 4) between patients with moderate versus severe events. Conclusions In populations comparable to this post-hoc analysis (orthopaedic surgery, median age 70 and ASA 2), we suggest a minimally important difference of 5 mg for 0–24 h postoperative iv morphine consumption., BACKGROUND: Morphine-sparing effects are often used to evaluate non-opioid analgesic interventions. The exact effect that would warrant the implementation of these interventions in clinical practice (a minimally important difference) remains unclear. We aimed to determine this with anchor-based methods.METHODS: This was a post hoc analysis of three studies investigating pain management after hip or knee arthroplasty (PANSAID [NCT02571361], DEX-2-TKA [NCT03506789] and Pain Map [NCT02340052]). The overall population was median aged 70, median ASA 2, 54% female. We examined the correlation between 0 and 24 h postoperative iv morphine equivalent consumption and the severity of nausea, vomiting, sedation and dizziness. The anchor was different severity degrees of these opioid-related adverse events. The primary outcome was the difference in morphine consumption between patients experiencing no versus only mild events. Secondary outcomes included the difference in morphine consumption between patients with mild versus moderate and moderate versus severe events. We used Hodges-Lehmann median differences, exact Wilcoxon-Mann-Whitney tests and quantile regression.RESULTS: The difference in iv morphine consumption was 6 mg (95% confidence interval: 4-8) between patients with no versus only mild events, 5 mg (2-8) between patients with mild versus moderate events and 0 mg (-4 to 4) between patients with moderate versus severe events.CONCLUSIONS: In populations comparable to this post-hoc analysis (orthopaedic surgery, median age 70 and ASA 2), we suggest a minimally important difference of 5 mg for 0-24 h postoperative iv morphine consumption.

OBJECTIVES: The DEX-2-TKA trial demonstrated that one and two doses of 24 mg intravenous dexamethasone reduced opioid consumption and pain after total knee arthroplasty (TKA). We aimed to investigate the prolonged effects of dexamethasone after the 48-h intervention period.DESIGN: This was a prospective, pre-planned questionnaire follow-up on postoperative days 3-7 of patients in the DEX-2-TKA trial that randomly received: DX1 (dexamethasone 24 mg + placebo), DX2 (dexamethasone 24 mg + dexamethasone 24 mg), and placebo (placebo + placebo) perioperatively and 24 h later.SETTING: A multicenter trial performed at five Danish hospitals.PARTICIPANTS: We analyzed 434 of 485 adult participants enrolled in the DEX-2-TKA trial.OUTCOME MEASURES: Primary outcome was difference between groups in average of all numerical rating scale (NRS) pain scores reported in the morning, at bedtime, and the daily average pain on postoperative days 3-7. Secondary outcomes were sleep quality and patient satisfaction.RESULTS: The median (interquartile range) pain intensity levels for postoperative days 3-7 were: DX2 3.2 (2.1-4.3); DX1 3.3 (2.3-4.1); and placebo 3.3 (2.5-4.7). Hodges-Lehmann median differences between groups were: 0 (95% confidence interval - 0.54 to 0.2), P = 0.38 between DX1 and placebo; 0.1 (-0.47 to 0.33), p = .87 between DX1 and DX2; and 0.1 (-0.6 to 0.13), p = .20 between DX2 and placebo. We found no relevant differences between groups on sleep quality on postoperative days 3-7 nor for patient satisfaction with the analgesic treatment.CONCLUSIONS: We found that neither one nor two doses of 24 mg intravenous dexamethasone demonstrated prolonged effects on overall pain or sleep quality on postoperative days 3-7 after total knee arthroplasty. We also found that dexamethasone had no effect on patient satisfaction.TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03506789 (main result trial).

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-s

Background: The patient-relevant minimal important difference for opioid consumption remains undetermined, despite its frequent use as primary outcome in trials on postoperative pain management. A minimal important difference is necessary to evaluate whether significant trial results are clinically relevant. Further, it can be used as effect size to ensure that trials are powered to find clinically relevant effects. By exploring the dose–response relationship between postoperative opioid consumption and opioid-related adverse effects, we aim to approximate the minimal important difference in opioid consumption anchored to opioid-related adverse effects. Methods: This is a post-hoc analysis of aggregated data from two clinical trials (PANSAID NCT02571361 and DEX2TKA NCT03506789) and one observational cohort study (Pain Map NCT02340052) on pain management after total hip and knee arthroplasty. The primary outcome is the Hodges–Lehmann median difference in opioid consumption between patients with no opioid-related adverse effects and patients experiencing the mildest degree of one or more opioid-related adverse effects (i.e., mild nausea, sedation and/or dizziness or vomiting). Secondary outcomes include the Hodges–Lehmann median difference in opioid consumption that corresponds to one point on a cumulated opioid-related adverse event 0–10 scale. Further, we will explore the proportion of patients that experience opioid-related adverse effects for consecutive opioid dose intervals of 2 mg iv morphine equivalents. Quantile regression will be used to assess any significant interactions with patient baseline characteristics. Conclusions: This study will hopefully bring us one step closer to determining relevant opioid reductions and thereby improve our understanding of intervention effects and planning of future trials.

BackgroundThe effects of glucocorticoids may include both genomic and rapid nongenomic effects. The potential rapid analgesic effect during surgery has not previously been investigated. We aimed to explore the effect of dexamethasone on intraoperative infusion rate of remifentanil in patients undergoing total knee arthroplasty surgery under general anaesthesia.MethodsIn this post-hoc subgroup analysis we included patients randomized in the DEX-2-TKA trial, who were operated under total intravenous anaesthesia with remifentanil and propofol. Trial medication, intravenous dexamethasone 24 mg or placebo, was administered immediately after anaesthesia onset. The primary outcome was the median weight-corrected infusion rate of remifentanil during surgery. Secondary outcomes included median weight-corrected infusion rate of propofol, median intraoperative bispectral index, and time spent in the post anaesthesia care unit.ResultsEighty-seven patients were included in the analysis of the primary outcome. A significantly higher remifentanil infusion rate was observed in the dexamethasone group compared with the placebo group, p=0.02. None of the secondary outcomes resulted in statistically significant differences between groups.ConclusionThis explorative post-hoc analysis of the randomized DEX-2-TKA trail showed that patients undergoing total knee arthroplasty surgery under general anaesthesia and who received dexamethasone, seemed to have a higher remifentanil infusion rate compared with patients who received placebo. The clinical implications of the potentially increased remifentanil infusion rate need to be validated and explored further. This article is protected by copyright. All rights reserved., Background The effects of glucocorticoids may include both genomic and rapid nongenomic effects. The potential rapid analgesic effect during surgery has not previously been investigated. We aimed to explore the effect of dexamethasone on intraoperative infusion rate of remifentanil in patients undergoing total knee arthroplasty (TKA) surgery under general anaesthesia. Methods In this post hoc subgroup analysis, we included patients randomised in the DEX-2-TKA trial, who were operated under total intravenous anaesthesia with remifentanil and propofol. Trial medication, intravenous dexamethasone 24 mg or placebo, was administered immediately after anaesthesia onset. The primary outcome was the median weight-corrected infusion rate of remifentanil during surgery. Secondary outcomes included median weight-corrected infusion rate of propofol, median intraoperative bispectral index and time spent in the post-anaesthesia care unit. Results Eighty-seven patients were included in the analysis of the primary outcome. A significantly higher remifentanil infusion rate was observed in the dexamethasone group compared with the placebo group, p = .02. None of the secondary outcomes resulted in statistically significant differences between groups. Conclusion This explorative post hoc analysis of the randomised DEX-2-TKA trail showed that patients undergoing TKA surgery under general anaesthesia and who received dexamethasone seemed to have a higher remifentanil infusion rate compared with patients who received placebo. The clinical implications of the potentially increased remifentanil infusion rate need to be validated and explored further.

Background Between 9% and 20% of patients experience moderate to severe persistent postoperative pain after total hip or knee arthroplasty. Severe immediate postoperative pain limits rehabilitation and is associated with the development of persistent postoperative pain. Therefore, perioperative analgesic and physiotherapeutic interventions are of interest to reduce persistent pain. In two systematic reviews with identical methodology, we aim to investigate the effects of (a) perioperative analgesic interventions and (b) physiotherapeutic interventions in reducing persistent pain after total hip and knee arthroplasty. Methods We will include randomised and cluster-randomised controlled trials on perioperative analgesic and physiotherapeutic interventions for patients undergoing elective total hip or knee arthroplasty for osteoarthritis. After contact with the authors, trials without pain data 3-24 months postoperatively will be excluded. Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists will be searched for eligible trials. Two authors will independently screen, extract data and assess the risk of bias. The primary outcome is pain scores 3-24 months postoperatively. Meta-analyses will be performed for interventions with two or more trials. We will conduct trial sequential analyses and assign Grading of Recommendations, Assessment, Development and Evaluation (GRADE) ratings. Conclusion No previous review on reduction of persistent postoperative pain has included non-pharmacological or invasive analgesic techniques. These two reviews with identical methodology will summarise the evidence of analgesic and physiotherapeutic perioperative interventions to prevent persistent pain. PROSPERO registration CRD42021284175.

Introduction. Day surgery is increasing, making efforts to improve safe and effective patient turnover of importance. We hypothesised that the introduction of a simple protocol, dictating that anaesthesia should be induced only immediately prior to surgical incision (after surgical preparations) would lead to reduced duration of anaesthesia and postanaesthesia care unit (PACU) stay. Methods. This was a retrospective, single-centre, procedure-specific, explorative feasibility study of patients undergoing anterior cruciate ligament surgery. Timestamps were collected from the electronic patient records within a three-month period before and after introduction of the protocol at the Copenhagen University Hospital, Bispebjerg and Frederiksberg. Clinical outcomes were assessed using the PACU score, based on the modified Aldrete discharge criteria. Results. A total of 44 patients were included in the after-, and 74 in the before-new-protocol group. The protocol was feasible in 44/59 patients (75%). The duration of anaesthesia was significantly reduced: 113 (± 26) versus 135 (± 32), mean difference 22 (11-33) minutes, p < 0.001. The duration of the PACU stay was significantly reduced: 103 (± 54) versus 80 (± 35), mean difference 23 (6-40) minutes, p = 0.01. No difference was observed in clinical outcomes. Conclusions. A simple protocol by which total intravenous anaesthesia was induced immediately prior to surgical incision was feasible, reduced the duration of anaesthesia and yielded a significant reduction in the PACU stay. Further studies with a randomised design are needed to confirm these preliminary findings.

Objective To investigate the effects of one and two doses of intravenous dexamethasone in patients after total knee arthroplasty. Design Randomised, blinded, placebo controlled trial with follow-up at 90 days. Setting Five Danish hospitals, September 2018 to March 2020. Participants 485 adult participants undergoing total knee arthroplasty. Intervention A computer generated randomised sequence stratified for site was used to allocate participants to one of three groups: DX1 (dexamethasone (24 mg)+placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was given preoperatively and after 24 hours. Participants, investigators, and outcome assessors were blinded. All participants received paracetamol, ibuprofen, and local infiltration analgesia. Main outcome measures The primary outcome was total intravenous morphine consumption 0 to 48 hours postoperatively. Multiplicity adjusted threshold for statistical significance was P<0.017 and minimal important difference was 10 mg morphine. Secondary outcomes included postoperative pain. Results 485 participants were randomised: 161 to DX1, 162 to DX2, and 162 to placebo. Data from 472 participants (97.3%) were included in the primary outcome analysis. The median (interquartile range) morphine consumptions at 0-48 hours were: DX1 37.9 mg (20.7 to 56.7); DX2 35.0 mg (20.6 to 52.0); and placebo 43.0 mg (28.7 to 64.0). Hodges-Lehmann median differences between groups were: −2.7 mg (98.3% confidence interval −9.3 to 3.7), P=0.30 between DX1 and DX2; 7.8 mg (0.7 to 14.7), P=0.008 between DX1 and placebo; and 10.7 mg (4.0 to 17.3), P<0.001 between DX2 and placebo. Postoperative pain was reduced at 24 hours with one dose, and at 48 hours with two doses, of dexamethasone. Conclusion Two doses of dexamethasone reduced morphine consumption during 48 hours after total knee arthroplasty and reduced postoperative pain.

We are grateful for the interest from Hu et al. in our article.1,2 There are different ways to select variables to be selected in a regression model, and there are different preferences among researchers. In general, p-values driven selection of covariates, such as stepwise selection of covariates, are being criticized by an increasing number of analysts, see Lydersen (2015) and references therein.3 Our initial list of candidate preventable risk factors were based on apriori judgment and potential clinical relevance, with use of conceptual frameworks as directed acyclic graphs to identify possible confounders.4 Then, we kept as candidate preventable risk factors only those that were statistically significant in the univariate analysis. For the rest, we have refrained from p-value driven selection of additional covariates. We did also ensure that no pairs of variables in the presented multivariable models were correlated to an extent that would lead to multicollinearity. We regard the step 2 and 3 proposed by you as having the potential to introduce similar problems as stepwise selection of covariates. We agree that the associations between postoperative haemoglobin and albumin and acute kidney injury are interesting. However, inclusion of postoperative albumin in a large multivariable model might have led to collider bias5 as several other covariates and the outcome all could lead to low albumin. Details of postoperative sepsis were unfortunately not available in our data set. We apologize for not clarifying these aspects clearly enough in the original article and once again want to express our gratitude to Hu et al. for their good questions.

BACKGROUND AND AIMS: Approximately 20% of patients having total knee arthroplasty (TKA) will experience chronic postoperative pain. Recently, preoperative pain facilitation has been associated with chronic pain after TKA, and gabapentin has been shown to decrease pain facilitation. The current study is a secondary follow-up of a primary RCT investigating the effect of gabapentin on acute postoperative pain after TKA and exploring the effect of pre- and perioperative administration of gabapentin on chronic postoperative pain and psychological state 3-4 years after TKA.METHODS: Patients scheduled for TKA were randomized to either gabapentin 1,300 mg/day, gabapentin 900 mg/day, or placebo daily from 2-h before and 6 days after operation. Pre- and 3-4 years postoperatively pain scores related to pain while walking, at rest, when flexing the hip or the knee were collected. At the same time, the pain catastrophizing scale (PCS) and hospital anxiety and depression scale subscales for anxiety (HADS-A) and depression (HADS-D) were collected.RESULTS: Lower postoperative pain while walking, flexing the hip, and at rest were found compared with preoperative scores (p<0.03), but these were not associated with gabapentin treatment (p>0.19). Significantly lower postoperative PCS and HADS-A scores were seen compared with preoperative scores (p<0.001), but these were not associated with gabapentin treatment (p>0.55).CONCLUSIONS: The current study found that pre- and perioperative administrations of gabapentin do not influence the pain or psychological state 3-4 years after TKA.IMPLICATIONS: The current study does not support that short-term pre- and perioperative use of gabapentin can reduce the development of chronic postoperative pain after TKA.

Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized (1:1:1) to either gabapentin 1300 mg/d (group A), gabapentin 900 mg/d (group B), or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery, and the secondary outcome was sedation 6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest and sedation during the first 48 hours and from days 2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, headache, visual disturbances, and adverse reactions. Pain upon ambulation (visual analog scale, mean [95% confidence interval]) 24 hours after surgery in group A vs B vs C was as follows: 41 [37-46] vs 41 [36-45] vs 42 [37-47], P = 0.93. Sedation (numeric rating scale, median [range]) 6 hours after surgery was as follows: 3.2 [0-10] vs 2.6 [0-9] vs 2.3 [0-9], the mean difference A vs C being 0.9 [0.2-1.7], P = 0.046. No between-group differences were observed in overall pain or morphine use the first 48 hours and from days 2-6. Sleep quality was better during the first 2 nights in group A and B vs C. Dizziness was more pronounced from days 2-6 in A vs C. More severe adverse reactions were observed in group A vs B and C. In conclusion, gabapentin may have a limited if any role in acute postoperative pain management of opioid-naive patients undergoing total knee arthroplasty and should not be recommended as a standard of care.

BACKGROUND AND PURPOSE: The concept of fast-track surgery has led to a decline in length of stay after total hip arthroplasty (THA) and total knee arthroplasty (TKA) to about 2-4 days. However, it has been questioned whether this is only achievable in selected patients-or in all patients. We therefore investigated the role of preoperative pain and functional characteristics in discharge readiness and actual LOS in fast-track THA and TKA.METHODS: Before surgery, hip pain (THA) or knee pain (TKA), lower-extremity muscle power, functional performance, and physical activity were assessed in a sample of 153 [corrected] patients and used as independent variables to predict the outcome (dependent variable) – readiness for hospital discharge – for each type of surgery. Discharge readiness was assessed twice daily by blinded assessorsRESULTS: Median discharge readiness and actual length of stay until discharge were both 2 days. Univariate linear regression followed by multiple linear regression revealed that age was the only independent predictor of discharge readiness in THA and TKA, but the standardized coefficients were small (≤ 0.03).INTERPRETATION: These results support the idea that fast-track THA and TKA with a length of stay of about 2-4 days can be achieved for most patients independently of preoperative functional characteristics.

BACKGROUND: Loading and contraction failure (muscular exhaustion) are strength training variables known to influence neural activation of the exercising muscle in healthy subjects, which may help reduce neural inhibition of the quadriceps muscle following total knee arthroplasty (TKA). It is unknown how these exercise variables influence knee pain after TKA.OBJECTIVE: To investigate the effect of loading and contraction failure on knee pain during strength training, shortly following TKA.DESIGN: Cross-sectional study.SETTING: Consecutive sample of patients from the Copenhagen area, Denmark, receiving a TKA, between November 2012 and April 2013.PARTICIPANTS: Seventeen patients, no more than 3 weeks after their TKA.MAIN OUTCOME MEASURES: In a randomized order, the patients performed 1 set of 4 standardized knee extensions, using relative loads of 8, 14, and 20 repetition maximum (RM), and ended with 1 single set to contraction failure (14 RM load). The individual loadings (kilograms) were determined during a familiarization session >72 hours prior. The patients rated their knee pain during each repetition, using a numerical rating scale (0-10).RESULTS: Two patients were lost to follow up. Knee pain increased with increasing load (20 RM: 3.1±2.0 points, 14 RM: 3.5±1.8 points, 8 RM: 4.3±2.5 points, P = 0.006), and repetitions to contraction failure (10% failure: 3.2±1.9 points, 100% failure: 5.4±1.6 points, P<0.001). Resting knee pain 60 seconds after the final repetition (2.7±2.4 points) was not different from that recorded before strength training (2.7±1.8 points, P = 0.88).CONCLUSION: Both loading and repetitions performed to contraction failure during knee- extension strength-training, increased post-operative knee pain during strength training implemented shortly following TKA. However, only the increase in pain during repetitions to contraction failure exceeded that defined as clinically relevant, and was v