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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)., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

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., Trial Registration: Clinicaltrials.gov NCT03506789., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Næstved, Slagelse, and Ringsted Hospitals’ Research Fund and the Department of Anaesthesiology at Næstved, Slagelse and Ringsted Hospitals for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Limited data exist on fast-track protocols in relation to revision knee arthroplasty. Hence, the aim of this study was to report length of stay (LOS), risk of LOS > 5 days and readmission ≤ 90 days after revision knee arthroplasty in centers with a well-established fast-track protocol in both primary and revision surgery., Methods: An observational cohort study from the Centre for Fast-track Hip and Knee Replacement and the Danish Knee Arthroplasty Register. We included elective aseptic major component revision knee arthroplasties consecutively from 6 dedicated fast-track centers from 2010 to 2018., Results: 1439 revision knee arthroplasties were analyzed, including 900 total revisions, 171 large partial revisions (revision of either femoral or tibia component) and 368 revisions of unicompartmental knee arthroplasty (UKA) to total knee arthroplasty (TKA). Mean age was 65 years (SD 10.9) and 66% were females. Mean LOS was 3.7 days (SD 3.9) in the study period, but decreased to 2.4 days (SD 1.3) in 2018. Risk factors for LOS > 5 days was ≥ 1 previous revision, use of walking aid, BMI > 35, ages < 50, 70-79 and ≥ 80 years, whereas revision of UKA to TKA and large partial revision were negatively associated. The 90-day readmission and mortality risk was 9.1% and 0.5%. Cardiac disease and use of walking aid were associated with increased risk of readmission ≤ 90 days., Conclusion: Elective aseptic major component revision knee arthroplasty using similar fast-track protocols as in primary TKA is safe with short and decreasing LOS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Optimization of post-operative pain treatment is of upmost importance. Multimodal analgesia is the main post-operative pain treatment principle, but the evidence on optimal analgesic combinations is unclear. With the "DEXamethasone twice for pain treatment after TKA" trial, we aim to investigate the role of one or two doses of glucocorticoid for post-operative pain treatment after total knee arthroplasty. To ensure transparency and minimization of bias, we present this article with a detailed statistical analysis plan, to be published before the last participant is enrolled., Methods: "DEXamethasone twice for pain treatment after TKA" (DEX-2-TKA) is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three intervention groups: single dose of iv dexamethasone 24 mg, two consecutive doses of iv dexamethasone 24 mg or matching iv placebo. All three intervention groups will receive paracetamol, NSAID (ibuprofen) and local infiltration analgesia. Participants, treatment providers, outcome assessors, data managers, statisticians and conclusion drawers will be blinded to the allocated intervention. The primary outcome is total opioid consumption (iv morphine milligram equivalents) 0-48 hours post-operatively. Secondary outcomes are (1) visual analogue scale pain levels: (a) during active 45 degrees flexion of the knee at 24 and 48 hours post-operatively, (b) at rest at 24 and 48 hours post-operatively, and (c) during 0-24 hours (highest score) and 24-48 hours post-operatively (highest score); and (2) the proportion of participants with one or more adverse events within 48 hours post-operatively., Discussion: The DEX-2-TKA trial will provide high quality data regarding benefits and harms of adding one or two high-doses of dexamethasone to a multimodal analgesic regimen., Trial Registration: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019)., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Multimodal analgesia is considered the leading principle for post-operative pain treatment, but no gold standard after total knee arthroplasty (TKA) exists., Aim: To investigate the beneficial and harmful effects of one or two doses of 24 mg intravenous dexamethasone (DXM) as part of a multimodal analgesic regimen (paracetamol, NSAID and perioperative local infiltration analgesia) after TKA. We hypothesize that addition of DXM will reduce post-operative opioid consumption., Methods: DEXamethasone twice for pain treatment after TKA is a randomized, blinded, three-group multicentre clinical trial. Participants will be randomized to one of three groups: placebo, single dose of DXM or two consecutive doses of DXM. Participants, treatment providers and investigators will be blinded to the allocated intervention. The primary outcome is total opioid consumption (units of morphine equivalents) 0-48 hours post-operatively., Inclusion Criteria: unilateral, primary TKA; age ≥18 years; American Society of Anesthesiologists-Score 1-3; Body Mass Index ≥18 and ≤40; for women-not pregnant; and written informed consent., Exclusion Criteria: allergy or contraindications against trial medication; daily use of high dose opioid and/or use of methadone/transdermal opioids; daily use of systemic glucocorticoids; dysregulated diabetes; and patients suffering from alcohol and/or drug abuse. Four-hundred-and-eighty-six eligible participants are needed to detect or discard a difference of 10 mg morphine equivalents 0-48 hours post-operatively maintaining a familywise error rate of 0.05 and a power of 90% for the three possible pairwise comparisons., Discussion: Recruiting is planned to commence September 2018 and expected to finish March 2020., Trial Registration: EudraCT: 2018-001099-39 (08/06-18); ClinicalTrials.gov: NCT03506789 (24/04-2019). Editorial Comment This is the protocol for the largest randomized clinical trial investigating the effect of one or two doses of dexamethasones on pain treatment after total knee arthroplasty. Due to the pragmatic and rigerous design this study will deliver results of high quality and external validity., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: To evaluate the effect of a single preoperative dose of 125 mg methylprednisolone (MP) on glycemic homeostasis early after fast-track total hip and knee arthroplasty., Methods: One-hundred thirty-four patients undergoing elective unilateral total hip arthroplasty and total knee arthroplasty were randomized (1:1) to preoperative intravenous MP 125 mg (group MP) or isotonic saline intravenous (group C). All procedures were performed under spinal anesthesia, using a standardized multimodal analgesic regime. The primary outcome was the change in plasma glucose 2 hours postoperatively, and secondary outcomes included plasma C-peptide concentrations, homeostatic model assessment (HOMA), HOMA-IR (insulin resistance), and HOMA-B (β-cell function). Fasting blood samples were collected at baseline and 2, 6 (nonfasting), 24, and 48 hours after surgery with complete samples from 122 patients (group MP = 62, group C = 60) for analyses., Results: MP patients had increased plasma glucose levels at 2 hours (adjusted mean [95% CI], 7.4 mmol·L [7.2-7.5] vs 6.0 mmol·L [5.9-6.2]; P = .023) and 6 hours (13.9 mmol·L [13.3-14.5] vs 8.4 mmol·L [7.8-9.0]; P < .001), and in plasma C-peptide 24 hours postoperatively (1675 pmol·L [1573-1778] vs 1248 pmol·L [1145-1351]; P < .001). An impaired insulin response was also observed in group MP as reflected by HOMA-B (P < .001). Additionally, HOMA-IR increased 24 hours postoperatively in group MP compared to group C (P < .001). Parameters were normalized 48 hours postoperatively., Conclusions: Preoperative administration of MP 125 mg resulted in a transient postoperative increase in plasma glucose and insulin resistance and impaired insulin secretion in response to hyperglycemia.

Preoperative glucocorticoid administration reduces the systemic inflammatory response. Pentraxin 3 (PTX3) is a novel inflammatory marker belonging to the humoral arm of innate immunity exerting a potentially protective host response. This study evaluated PTX3 and other complement marker changes after preoperative methylprednisolone (MP) early after total knee arthroplasty (TKA). Seventy patients were randomized (1 : 1) to preoperative intravenous (i.v.) MP 125 mg (group MP) or isotonic saline i.v. (group C). The outcomes included change in plasma PTX3, mannose-binding lectin (MBL), ficolins (ficolin-1, -2 and -3), complement components (C4 and C3), terminal complement complex (TCC) and C-reactive protein (CRP) concentrations. Blood samples were analysed at baseline and 2, 6, 24 and 48 h after surgery with complete sampling from 63 patients for analyses. MP resulted in an increase in circulating PTX3 compared to saline from baseline to 24 h postoperatively (P < 0·001), while MP reduced the systemic inflammatory response (CRP) 24 and 48 h postoperatively (P < 0·001). However, the small postoperative changes in MBL, ficolin-1, -2 and -3, C4, C3 and TCC concentrations did not differ between groups (P > 0·05). In conclusion, preoperative MP 125 mg increased circulating PTX3 and reduced the general inflammatory response (CRP) early after TKA, but did not affect other complement markers., (© 2017 British Society for Immunology.)

Background: Revision of infected knee arthroplasties is associated with high failure rates (30-40%). An understanding of the microbiology is important to optimize treatment and outcome. We describe microbiological diagnostic practice and diagnosis in revision of infected knee arthroplasties., Methods: One hundred and two partial revisions (open debridement and exchange of tibial insert) and 213 two-stage procedures performed due to infection in 275 patients from 1 July 2011 to 30 June 2013 were included and analysed by linkage to data from a nationwide registry on microbiological test results., Results: 78 (24.8%) revisions were culture negative, 192 (60.9%) showed monomicrobial growth and 43 (14.3%) polymicrobial growth. Staphylococcus aureus was the most frequent isolate in mono-culture in 70 (22.2%) revisions and in polymicrobial culture in 15 revisions with a total frequency of 27.0%. Only one case (1.4%) of methicillin-resistance was registered. Coagulase-negative staphylococci (CoNS) were frequent, sole pathogen in 65 revisions and in polymicrobial cultures in 28 revisions with a total frequency of 29.5%. A pre-operative knee aspiration was performed in 50% and preoperative blood cultures were performed in 22% of cases. In 73% of the preoperative knee-aspirations bacteriological findings were fully or partially in accordance with intraoperative cultures. In 54% of the later re-revisions due to infection (treatment-failures) the cultured species differed from or was not detected at index revision surgery., Conclusions: The 25% culture negative cases in combination with only 50% preoperative knee aspirations and prevailing high failure rates confirm the need for improvement of diagnostic practice and treatment of infected knee arthroplasties.

Background and purpose - Patients undergoing total knee arthroplasty (TKA) face challenges related to postoperative reduction in knee-extension strength. We evaluated whether inhibition of the inflammatory response by a single preoperative dose of methylprednisolone (MP) reduces the pronounced loss of knee-extension strength at discharge after fast-track TKA. Patients and methods - 70 patients undergoing elective unilateral TKA were randomized (1:1) to preoperative intravenous (IV) MP 125 mg (group MP) or isotonic saline IV (group C). All procedures were performed under spinal anesthesia without tourniquet, and with a standardized multimodal analgesic regime. The primary outcome was change in knee-extension strength from baseline to 48 hours postoperatively. Secondary outcomes were knee joint circumference, functional performance using the Timed Up and Go (TUG) test, pain during the aforementioned tests, rescue analgesic requirements, and plasma C-reactive protein (CRP) changes. Results - 61 patients completed the follow-up. The loss in quadriceps muscle strength was similar between groups; group MP 1.04 (0.22-1.91) Nm/kg (-89%) vs. group C 1.02 (0.22-1.57) Nm/kg (-88%). Also between-group differences were similar for knee circumference, TUG test, and pain scores. MP reduced the inflammatory response (CRP) at 24 hours postoperatively; group MP 33 (IQR 21-50) mg/L vs. group C 72 (IQR 58-92) mg/L (p < 0.001), and 48 hours postoperatively; group MP 83 (IQR 56-125) mg/L vs. group C 192 (IQR 147-265) mg/L (p < 0.001), respectively. Interpretation - Preoperative systemic administration of MP 125 mg did not reduce the pronounced loss of knee-extension strength or other functional outcomes at discharge after fast-track TKA despite a reduced systemic inflammatory response.