IMPORTANCE Multimodal postoperative analgesia is widely used but lacks evidence of benefit. OBJECTIVE Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens. DESIGN, SETTING, AND PARTICIPANTS Randomized, blinded, placebo-controlled, 4-group trial in 6Danishhospitalswith90-dayfollow-upthatincluded556patientsundergoingtotalhiparthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018. INTERVENTIONS Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS-PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery. MAIN OUTCOMES AND MEASURES Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P < .0042; minimal clinically important difference, 10 mg), and proportion of patients with 1 or more serious adverse events (SAEs) within 90 days (multiplicity-adjusted thresholds for statistical significance, P < .025). RESULTS Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM + IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM + IBU. The median difference in morphine consumption between the PCM + IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P < .001); for the PCM-alone group vs HS-PCM + IBU, 8 mg (99.6% CI, −1 to 14; P = .001); and for the PCM + IBU group vs IBU alone, 6 mg (99.6% CI, −2 to 16; P = .002). The difference in morphine consumption was not statistically significant for the PCM + IBU group vs HS-PCM + IBU (8 mg [99.6% CI, −2 to 16]; P = .005) or for the PCM-alone group vs IBU alone (10 mg [99.6% CI, −2 to 16]; P = .004) after adjustment for multiple comparisons and 2 co-primary outcomes. There was no significant difference between the IBU-alone group vs HS-PCM + IBU (2 mg [99.6% CI, −10 to 7]; P = .81). The proportion of patients with SAEs in groups receiving IBU was 15%, and in the PCM-alone group, was 11%. The relative risk of SAE was 1.44 (97.5% CI, 0.79 to 2.64; P = .18). CONCLUSIONS AND RELEVANCE Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia.

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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 .

PurposeWe described the settings, organization, content, and data quality of the Danish Knee Arthroplasty Register (DKR), as well as the incidence and the first results of the knee replacement procedures captured by the DKR. Our aim was to draw researchers’ attention to the DKR and its potential use in clinical epidemiological research.Patients and methodsThe DKR has collected data on all knee replacement procedures performed in Denmark since 1997. The validity of the register was compared with the Danish National Registry of Patients (DNRP). Incidence rate was calculated per 100,000 inhabitants. Implant survival was estimated by Kaplan–Meier method. Cox regression analyses were used to estimate the relative risk (RR) for revision with a 95% confidence interval (CI).ResultsA total of 62,586 primary knee arthroplasties and 6,683 revisions were registered in the DKR between January 1, 1997 and December 31, 2010. More than 90% of the private and public hospitals performing knee replacement surgery in Denmark have entered data to the DKR. Registration completeness of primary procedures and revisions has increased since the DKR initiation and was 88% in 2010 for both procedures, compared with registration in the DNRP. For primary knee arthroplasties, the annual incidence rate increased from 35.8 in 1997 to 155.2 in 2010 per 100,000 inhabitants. Incidence was higher in females than in males during the entire study period, and increased with age for both sexes. The overall implant survival after 14 years was 89% irrespective of diagnosis for surgery. Male patients had higher revision risk than females, and revision risk decreased with increasing age. Risk for any revision was higher for uncemented implants (RR = 1.48; 95% CI: 1.32–1.66), and lower for hybrid implants (RR = 0.84; 95% CI: 0.75–0.95) compared to cemented implants. Implant survival did not improve but remained the same throughout the study period when comparing patients operated in the periods 1997–2000 versus 2001–2003, 2004–2006, and 2007–2010.ConclusionThe DKR is a valuable tool for quality monitoring and research in knee arthroplasty surgery due to the high quality and completeness of prospective, routinely collected data. Large population-based epidemiological studies can be performed in order to study trends as well as risk factors for poor clinical outcome following knee arthroplasty surgery.

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