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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.

Background Acute and persistent pain after surgery is well described. However, no large-scale studies on immediate postoperative pain in the operating room (OR) exist, hindering potential areas of research to improve clinical outcomes. Thus, we aimed to describe the occurrence and severity of immediate postoperative pain in a large, unselected cohort. Methods This was a prospective cohort study, encompassing all procedures in 31 public hospitals in the Danish Realm, during a 5-day period including the weekend. Data on procedures and anesthesia were collected and the main outcome was occurrence of moderate or severe pain in the OR. Secondary outcomes included pain, sedation and nausea in the OR or during the first 15 min in the postanesthesia care unit (PACU) including relevant risk factors. Descriptive and logistic regression statistics were used. Results A total of 3675 procedures were included for analysis (87% inclusion rate). Moderate or severe pain occurred in 7.4% (95% CI 6.5% to 8.3%) of cases in the OR immediately after awakening, rising to 20.2% in the OR and/or PACU. Large intraprocedure and interprocedure variations occurred (0.0%–37.5%), and in 20% of cases with epidural-general anesthesia patients experienced moderate or severe pain. Independent risk factors were female sex, younger age, preoperative pain, daily opioid use and major surgical procedures. Conclusion Moderate or severe pain in the immediate postoperative phase occurred in 20% of all cases with procedure and anesthesiological technique variations, suggesting a need for identification of relevant procedure-specific risk factors and development of preventive treatments.

Background: The “Paracetamol and Ibuprofen in Combination” (PANSAID) trial showed that combining paracetamol and ibuprofen resulted in lower opioid consumption than each drug alone and we did not find an increase in risk of harm when using ibuprofen vs paracetamol. The aim of this subgroup analysis was to investigate the differences in benefits and harms of the interventions in different subgroups. We hypothesized that the intervention effects would differ in subgroups with different risk of pain or adverse events. Methods: In these pre-planned subgroup analyses of the PANSAID trial population, we assessed subgroup heterogeneity in intervention effects between (a) subgroups (sex, age, use of analgesics, American Society of Anesthesiologists (ASA) score, and type of anesthesia) and morphine consumption, and (b) subgroups (sex, age, use of non-steroidal anti-inflammatory drugs (NSAIDs), and ASA score) and serious adverse events. Results: Test of interaction between age and the pairwise comparison between paracetamol 1 g vs paracetamol 0.5 g + ibuprofen 200 mg (P =.009) suggested lower morphine consumption in patients >65 years. However, post hoc analyses of related outcomes showed no interaction for this pairwise comparison. All other tests of interaction regarding both benefit and harm were not statistically significant. Conclusion: These pre-planned subgroup analyses did not suggest that patients in the investigated subgroups benefitted differently from a basic non-opioid analgesic regimen consisting of paracetamol and ibuprofen. Further, there was no evidence of subgroup heterogeneity regarding harm and use of ibuprofen. Because of reduced statistical power in subgroup analyses, we cannot exclude clinically relevant subgroup heterogeneity.

To determine the long-term sensitivity of the Greenland ice sheet to a warmer climate, we explored how it responded to the Holocene thermal maximum (8–5 cal. kyr B.P.; calibrated to calendar years before present, i.e., A.D. 1950), when lake records show that local atmospheric temperatures in Greenland were 2–4 °C warmer than the present. Records from five new threshold lakes complemented with existing geological data from south of 70°N show that the ice margin was retracted behind its present-day extent in all sectors for a limited period between ca. 7 and 4 cal. kyr B.P. and in most sectors from ca. 1.5 to 1 cal. kyr B.P., in response to higher atmospheric and ocean temperatures. Ice sheet simulations constrained by observations show good correlation with the timing of minimum ice volume indicated by the threshold lake observations; the simulated volume reduction suggests a minimum contribution of 0.16 m sea-level equivalent from the entire Greenland ice sheet, with a centennial ice loss rate of as much as 100 Gt/yr for several millennia during the Holocene thermal maximum. Our results provide an estimate of the long-term rates of volume loss that can be expected in the future as regional air and ocean temperatures approach those reconstructed for the Holocene thermal maximum., To determine the long-term sensitivity of the Greenland ice sheet to a warmer climate, we explored how it responded to the Holocene thermal maximum (8–5 cal. kyr B.P.; calibrated to calendar years before present, i.e., A.D. 1950), when lake records show that local atmospheric temperatures in Greenland were 2–4 °C warmer than the present. Records from five new threshold lakes complemented with existing geological data from south of 70°N show that the ice margin was retracted behind its present-day extent in all sectors for a limited period between ca. 7 and 4 cal. kyr B.P. and in most sectors from ca. 1.5 to 1 cal. kyr B.P., in response to higher atmospheric and ocean temperatures. Ice sheet simulations constrained by observations show good correlation with the timing of minimum ice volume indicated by the threshold lake observations; the simulated volume reduction suggests a minimum contribution of 0.16 m sea-level equivalent from the entire Greenland ice sheet, with a centennial ice loss rate of as much as 100 Gt/yr for several millennia during the Holocene thermal maximum. Our results provide an estimate of the long-term rates of volume loss that can be expected in the future as regional air and ocean temperatures approach those reconstructed for the Holocene thermal maximum.