The OPI•AID Zone Tool as a composite outcome for postoperative pain management quality-A protocol for an observational pilot study.

BACKGROUND: Managing postoperative pain while minimizing opioid-related adverse drug events (ORADEs) remains a significant challenge. The OPI•AID Zone Tool is proposed as a novel clinical decision support tool that - both graphically and in a scoring-system - represents the relationship between pain management and the occurrence of ORADEs, aiming to enhance patient outcomes in postoperative care. The OPI•AID Zone Tool places pain score on the x-axis and an ORADE score on the y-axis, and stratifies patients into five zones to reflect the composite impact of pain severity and ORADEs on the quality of postoperative patient care. The study will have two key aims: (1) to explore whether the OPI•AID Zone Tool can function as a composite outcome measure for postoperative pain and ORADEs, and (2) to evaluate the use of the OPI•AID Zone Tool in visual presentations and for evaluation of patients' postoperative pain management quality. METHODS: This prospective observational cohort study will include 200 adults undergoing various surgical procedures in general anesthesia with a subsequent stay in the post-anesthesia care unit (PACU) at Bispebjerg Hospital, Denmark. Substudy 1 primary outcome: To assess whether a zone score in the OPI•AID Zone Tool is associated with patient-perceived health (EQ VAS), quality of recovery (QoR-PACU), and time to discharge readiness in PACU, and if the zone score has a stronger association than pain and ORADE score in themselves. Substudy 2 primary outcome: To assess how the use of intraoperative non-opioid analgesics impact where patients are placed in the OPI•AID Zone Tool's XY scatterplot right after surgery. To assess if patients who receive more comprehensive non-opioid analgesic basic regimens, generally fall into lower zones. CONCLUSION: The OPI•AID Zone Tool could potentially be a valuable clinical decision-making tool for optimizing postoperative care by simultaneously addressing pain management and the risk of ORADEs. By computing a composite measure of these two critical outcomes, the tool could guide more nuanced and patient-centered analgesic regimens, potentially improving patient satisfaction and operational efficiency in postoperative settings. The tool's applicability will be explored in this observational pilot and followed up in a planned series of studies (opiaid.dk).

Minimal important difference in postoperative morphine consumption after hip and knee arthroplasty using nausea, vomiting, sedation and dizziness as anchors.

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.

Prolonged effects of dexamethasone following total knee arthroplasty: A pre-planned sub-study of the DEX-2-TKA trial.

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).

Opioids and personalized analgesia in the perioperative setting: A protocol for five systematic reviews.

BACKGROUND: Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure-specific pain management, efforts regarding personalized pain treatment are increasing. The OPI•AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment. METHODS: Inclusion of adult populations in English-written studies. Review-specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant). CONCLUSION: These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPI•AID) that will be validated and tested clinically against standard of care.

Minimal important difference in opioid consumption based on adverse event reduction-A study protocol.

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.

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

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-saving.

Effect of dexamethasone on intraoperative remifentanil dose in total knee arthroplasty surgery under general anaesthesia.

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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05002361 (12 August 2021).

Perioperative prevention of persistent pain after total hip and knee arthroplasty-Protocol for two systematic reviews.

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.

Oral Midodrine Hydrochloride for Prevention of Orthostatic Hypotension during Early Mobilization after Hip Arthroplasty: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Early postoperative mobilization is essential for rapid recovery but may be impaired by orthostatic intolerance (OI) and orthostatic hypotension (OH), which are highly prevalent after major surgery. Pathogenic mechanisms include an insufficient postoperative vasopressor response. The oral α-1 agonist midodrine hydrochloride increases vascular resistance, and the authors hypothesized that midodrine would reduce the prevalence of OH during mobilization 6 h after total hip arthroplasty relative to placebo. METHODS: This double-blind, randomized trial allocated 120 patients 18 yr or older and scheduled for total hip arthroplasty under spinal anesthesia to either 5 mg midodrine hydrochloride or placebo orally 1 h before mobilization at 6 and 24 h postoperatively. The primary outcome was the prevalence of OH (decrease in systolic or diastolic arterial pressures of > 20 or 10 mmHg, respectively) during mobilization 6 h after surgery. Secondary outcomes were OI and hemodynamic responses to mobilization at 6 and 24 h. RESULTS: At 6 h, 14 (25%; 95% CI, 14 to 38%) versus 23 (39.7%; 95% CI, 27 to 53%) patients had OH in the midodrine and placebo group, respectively, relative risk 0.63 (0.36 to 1.10; P = 0.095), whereas OI was present in 15 (25.0%; 15 to 38%) versus 22 (37.3%; 25 to 51%) patients, relative risk 0.68 (0.39 to 1.18; P = 0.165). At 24 h, OI and OH prevalence did not differ between groups. CONCLUSIONS: Preemptive use of oral 5 mg midodrine did not significantly reduce the prevalence of OH during early postoperative mobilization compared with placebo. However, further studies on dose and timing are warranted since midodrine is effective in chronic OH conditions.

Role of preoperative pain, muscle function, and activity level in discharge readiness after fast-track hip and knee arthroplasty.

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 assessors RESULTS: 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.

Readmission and mortality before and after introduction of orthogeriatric home visits: A retrospective cohort study in hip fracture patients.

INTRODUCTION: Orthogeriatric collaboration in hip fracture patients during admission is well established, however, orthogeriatric involvement after discharge is not common. The aim of this study was to explore the association of orthogeriatric home visits with 30-day and 120-day readmission and mortality in ≥ 65-year-old patients surgically treated for hip fractures. MATERIALS AND METHODS: A cohort of patients who underwent acute hip fracture surgery in an usual care period from January 2018 to December 2018 was compared with a cohort of patients in an intervention period from June 2020 to June 2021. During the intervention period, patients were offered orthogeriatric home visits at day 2 and 9 after discharge. The home visits were performed by orthogeriatric nurses, in close collaboration with geriatricians and orthopedic surgeons based in the local hospital. Readmission was defined as ≥ 12 h hospital stay, regardless of reason. For the main analysis, we applied Cox-regression models adjusted for age, sex, New Mobility Score, Cumulated Ambulation Score regained, cognitive function, Charlson Comorbidity Index, complications, medication, discharge destination and emergency department visits. RESULTS: In total, 292 patients were included during the usual care period, and 308 patients during the intervention period. Thirty- and 120-day readmission rates were 27.7 % and 41.4 % in the usual care cohort vs. 21.8 % and 35.1 % in the home visit cohort. Adjusted Hazard Ratios for readmission in the intervention cohort after 30 and 120 days were 0.67 (CI95 %: 0.48-0.93) and 0.71 (CI95 %: 0.54-0.93) respectively. Thirty- and 120-day mortality rates were 7.2 % and 20.9 % in the usual care cohort versus 5.8 % and 13.3 % in the intervention cohort. Adjusted Hazard Ratios for mortality in the intervention cohort after 30 and 120 days were 0.68 (CI95 %: 0.35-1.31) and 0.56 (CI95 %: 0.37-0.84) respectively. CONCLUSIONS: In a period where hip fracture patients were offered two home visits after discharge, we observed lower 30- and 120- day readmission, and lower 120-day mortality, calling for more studies with a randomized design.

Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial.

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 paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. INTERPRETATION: In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. FUNDING: The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

Paracetamol, ibuprofen and dexamethasone for pain treatment after total hip arthroplasty: protocol for the randomised, placebo-controlled, parallel 4-group, blinded, multicentre RECIPE trial.

INTRODUCTION: Multimodal analgesia with paracetamol, non-steroidal anti-inflammatory drug and glucocorticoid is recommended for hip arthroplasty, but with uncertain effects of the different combinations. We aim to investigate benefit and harm of different combinations of paracetamol, ibuprofen and dexamethasone following total hip arthroplasty. METHODS AND ANALYSIS: RECIPE is a randomised, placebo-controlled, parallel 4-group, blinded trial with 90-day and 1-year follow-up performed at nine Danish hospitals. Interventions are initiated preoperatively and continued for 24 hours postoperatively. Eligible participants undergoing total hip arthroplasty are randomised to:group A: oral paracetamol 1000 mg × 4+oral ibuprofen 400 mg × 4+intravenous placebo; group B: oral paracetamol 1000 mg × 4+intravenous dexamethasone 24 mg+oral placebo; group C: oral ibuprofen 400 mg × 4+intravenous dexamethasone 24 mg+oral placebo; group D: oral paracetamol 1000 mg × 4+oral ibuprofen 400 mg × 4+intravenous dexamethasone 24 mg.Primary outcome is cumulative opioid consumption at 0-24 hours. Secondary outcomes are pain at rest, during mobilisation and during a 5 m walk and adverse events. Follow-up includes serious adverse events and patient reported outcome measures at 90 days and 1 year. A total of 1060 participants are needed to demonstrate a difference of 8 mg in 24-hour morphine consumption assuming an SD of 24.5 mg, a risk of type I errors of 0.0083 and a risk of type 2 errors of 0.2. Primary analysis will be a modified intention-to-treat analysis.With this trial we aim to verify recommendations for pain treatment after total hip arthroplasty, and investigate the role of dexamethasone as an analgesic adjuvant to paracetamol and ibuprofen. ETHICS AND DISSEMINATION: This trial is approved by the Region Zealand Committee on Health Research Ethics (SJ-799). Plans for dissemination include publication in peer-reviewed journals and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: NCT04123873.

Effect of dexamethasone as an analgesic adjuvant to multimodal pain treatment after total knee arthroplasty: randomised clinical trial.

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.

Surgical preparation and draping prior to induction of total intravenous anaesthesia.

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 less-than 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. FUNDING: departmental only. TRIAL REGISTRATION: not relevant.

The influence of pre- and perioperative administration of gabapentin on pain 3-4 years after total knee arthroplasty.

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.

Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty: a randomized, double-blind, placebo-controlled dose-finding study.

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.

Knee pain during strength training shortly following fast-track total knee arthroplasty: a cross-sectional study.

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 very short-lived. TRIAL REGISTRATION: ClinicalTrials.gov NCT01729520.