Elective Hip Replacement Surgery Research Articles

Association between perioperative blood transfusion and early postoperative cognitive dysfunction in aged patients following total hip replacement surgery

Introduction. Accumulating evidence suggests that enhanced inflammatory responses contribute to the pathogenesis of postoperative cognitive dysfunction (POCD). Blood transfusion can trigger an enhancement of acute inflammatory responses. Therefore, we hypothesized that perioperative blood transfusion is associated with a higher risk of POCD in aged patients following total hip replacement surgery.Material and methods. Patients older than 65 years undergoing elective total hip replacement surgery were enrolled from October 2011 to December 2012. Neurocognitive tests were evaluated at baseline and at 7 d after surgery by a Mini-Mental State Test. Multivariate logistic regression analysis was used to determine risk factors associated with POCD.Results. Fifty-six patients (27.3%) developed POCD 7 d postoperatively. Patients who developed POCD were older, had a lower education level and preoperative hemoglobin concentration, had more blood loss, and had a lower body weight (p < 0.05). Patients with POCD were more likely to receive red blood cells (RBCs) transfusion (51.8% versus 31.5%; p < 0.05). A multivariable logistic regression model identified older age, lower education level, and perioperative blood transfusion of more than 3 units as independent risk factors for POCD 7 d postoperatively.Conclusion. Our data suggested that perioperative blood transfusion of more than 3 units of RBCs is an independent risk factor for POCD in aged patients following total hip replacement surgery.

Lower limb orthopaedic surgery results in changes to coagulation and non-specific inflammatory biomarkers, including selective clinical outcome measures

BackgroundWith an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective).MethodsTest subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever.ResultsTHR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections.ConclusionsThe most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care.

Preoperative insulin resistance reduces complications after hip replacement surgery in non-diabetic patients

BackgroundInsulin resistance negatively affects the outcome of surgery in patients with type 2 diabetes. This association is often believed to be present in other patient populations as well, but studies are lacking on the influence of preoperative insulin resistance on the clinical course of surgery in non-diabetic patients.MethodsSixty non-diabetic patients with a mean age of 68 years underwent a 75-min intravenous glucose tolerance test (IVGTT) one day before and after elective hip replacement surgery. Patients were regarded to be either insulin resistant (< median insulin sensitivity) or not (> median insulin sensitivity). Hypotensive events occurring in the postoperative care unit and complications in the orthopedic ward were recorded. Fatigue and well-being were assessed via questionnaires.ResultsA total of 52 patients were included in the final analysis. Insulin resistance before surgery was associated with a lower risk of arterial hypotension in the postoperative care unit (systolic pressure < 80 mmHg; P < 0.05) and with fewer complications in the orthopedic ward (mean 1.9 versus 1.2 per operation, P < 0.01), particularly with respect to nausea/vomiting (P < 0.04) and arterial hypotension (P < 0.05). Fewer of these patients had more than one complication (23% versus 58%, P < 0.001), while no statistical link between preoperative insulin resistance and fatigue or well-being was evident. Insulin resistance, when measured one day postoperatively, did not correlate with the number of complications.ConclusionsPreoperative insulin resistance offers some benefit in the postoperative period and early convalescence in non-diabetic patients who undergo hip replacement surgery.

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects

Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban. This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels - apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily- with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT). Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ~3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3-1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration-time profile. Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures.

Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery: A double-blind, randomised controlled clinical trial

Surgery initiates a series of physiological stress processes in the body, inducing transient insulin resistance. Preoperative carbohydrate treatment can reduce the latter phenomenon. We investigated the effects of carbohydrate loading on insulin sensitivity and beta-cell function after elective hip replacement. Twenty-three nondiabetic patients (mean age of 68 years) who underwent elective hip replacement surgery participated in this double-blind controlled study. The patients were randomised to a nutrition group, which ingested a carbohydrate-rich fluid (50 kcal/100 ml) (Preop(®)), or a control group (tap water flavoured with lemon) 800 ml + 400 ml before the surgery. The insulin response (beta-cell function) and the insulin sensitivity were measured with an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic euglycaemic glucose clamp, respectively, one day before and two days after the surgery. Insulin sensitivity decreased by 51% (median; 25-75th percentiles 35-61) after ingesting Preop(®) and by 39% (21-51) after ingesting in the control group (n.s.). The postoperative IVGTT in the nutrition group was followed by a significantly larger area under the curve (AUC) for plasma insulin (+54% versus the preoperative IVGTT) compared to the control group (+7%). This difference was already apparent during the first phase (0-10 min) of insulin secretion (+20 and -21%, respectively; P < 0.05). The patients randomised to the carbohydrate oral fluid or the water prior to the surgery demonstrated a significant but similar decrease in insulin sensitivity. The carbohydrates increased the beta-cell function as a compensatory response to the disposition index, resulting in a smaller reduction in surgery-induced insulin resistance compared to the tap water. The study was registered at http://www.clinicaltrials.gov (NCT01774084).

Use of analgesics and risk of death after discharge from elective hip or knee replacement - a nationwide cohort study

Purpose: Individual drugs for pain management may have different risk profile, especially among elderly individuals. We investigated the risk of mortality with use of analgesics during the first six months after discharge from elective hip or knee replacement surgery. Methods: Through cross-linkage of Danish nationwide administrative registers, we identified patients discharged alive after elective hip or knee replacement between mid 2004 and end 2009. Risk of mortality during the first six months associated with use of diclofenac, ibuprofen, naproxen, tramadol, and morphine was analyzed by multivariable time-dependent Cox proportional hazard regression. Results: In total 28,467 patients were included (60% women and mean age 69.0 (inter quartile range 61.6-76.5) years) of which 15,573 (55%) had a total hip replacement. A total of 2,459 patients received diclofenac, 7,044 ibuprofen, 379 naproxen, 9,851 tramadol, 11,696 paracetamol, and 6,679 morphine. During follow-up 380 patients died (21 in diclofenac, 37 in ibuprofen, 2 in naproxen, 80 in tramadol, 206 in paracetamol, and 87 in morphine treatment). The adjusted Cox regression analysis demonstrated that morphine and diclofenac were associated with increased mortality (Figure) while ibuprofen, naproxen, tramadol and paracetamol were not associated with increased risk. ![Figure][1] Figure 1 Conclusions: Treatment with diclofenac or morphine during the first six months after discharge from elective hip or knee replacement was associated with increased mortality-risk. Awareness on potential risk of adverse events associated with these drugs after hip- or knee-replacement surgery is warranted. [1]: pending:yes

A randomised controlled trial to evaluate the efficacy of a health maintenance clinic intervention for patients undergoing elective primary total hip and knee replacement surgery

AimThis paper is the report of a study exploring the efficacy of a health maintenance clinic intervention for patients with severe osteoarthritis of the hip and knee whilst awaiting primary joint replacement surgery. BackgroundHistorically in the UK patients with severe osteoarthritis waited many months for their hip and knee replacement surgery. The waiting time was often in the absence of support and advice relating to symptom management. A health maintenance intervention was developed to provide support to patients whilst awaiting their joint replacement and to optimise their health status ahead of the procedure. MethodsA randomised control trial (RCT) compared usual care (pre-operative assessment only) to a new intervention (health maintenance clinic plus pre-operative assessment). A sample of 250 people with osteoarthritis waiting for joint replacement were recruited via an orthopaedic out-patient department between 2005 and 2006. To assess the effectiveness of the intervention outcome, measures were recorded at two points in time (on referral to the waiting list and at 2weeks prior to surgery). ResultsNo significant difference between the total score on the disease specific outcome measure was found (p=0.69). However, participants in the experimental group were significantly more satisfied with their care (p=0.001) and had fewer incidences of postponement of surgery (p=0.002). ConclusionA tailored intervention for symptom management in the pre-operative period increases patient satisfaction which may have a positive impact on concordance and postoperative recovery. Also, reducing the number of surgical postponements has a positive economic value for health care providers.

Massive Left Atrial Thrombus in a Patient With Rheumatic Mitral Stenosis and Atrial Fibrillation While Anticoagulated With Dabigatran

Dabigatran is an oral direct thrombin inhibitor licensed for use by the Food and Drug Administration.1,2 This novel anticoagulant is effective and approved for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation (AF) and prevention of venous thromboembolism in adults receiving elective total hip or knee replacement surgery.1,2 These images present a cautionary account of failed dabigatran anticoagulation in a patient with valvular AF: an indication for which its use has not been approved. A 50-year-old female with severe rheumatic mitral stenosis underwent open mitral valvotomy under cardiopulmonary bypass 25 years prior. On subsequent annual surveillance, she remained asymptomatic and her mitral stenosis remained moderate on echocardiography with a mean transmitral gradient of 8 mm Hg. Permanent AF was previously diagnosed 12 months earlier, and she was commenced on warfarin and metoprolol. She had stable anticoagulation monitoring, no bleeding complications, and normal renal function, but was needle-phobic with psychological …

Novel oral anticoagulants: clinical pharmacology, indications and practical considerations

Novel oral anticoagulants are approved in several indications: rivaroxaban, apixaban, and dabigatran for the prevention of venous thromboembolism after elective hip or knee replacement surgery, and edoxaban for hip or knee replacement surgery and hip fracture surgery (in Japan only); rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE; and rivaroxaban, apixaban, and dabigatran for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. These agents overcome some limitations of traditional anticoagulants, are suggested to have no requirement for routine coagulation monitoring, and are administered orally. Rivaroxaban, apixaban, and dabigatran have different pharmacological characteristics, and guidance is needed on optimum doses and dosing intervals and the effects of renal or hepatic impairment, age, food, and other drugs. Dabigatran has stricter prescribing advice than rivaroxaban or apixaban for patients with moderate-to-severe renal impairment. All three drugs have restrictions on use in patients with hepatic impairment. Apixaban requires twice-daily dosing in all indications, whereas rivaroxaban and dabigatran are dosed once- or twice-daily depending on indication. Although head-to-head comparisons are lacking, the novel oral anticoagulants may show favorable cost-benefit relations compared with traditional vitamin K antagonists or no therapy. This review summarizes the pharmacology of rivaroxaban, apixaban, edoxaban, and dabigatran, and the indications for which they are approved. Issues regarding the optimization of the use of these anticoagulants for the management of thromboembolic disorders will also be discussed.

Documenting informed consent in elective hip replacement surgery: a simple change in practice

Adequate documentation of informed consent is an important aspect of many doctors' work and failings in this area may result in patient dissatisfaction or litigation. In 2009 the documentation of risks and complications on the consent forms of patients undergoing primary hip replacement was audited at a specialist centre. Following this audit procedure-specific complication stickers were introduced in an attempt to improve the documentation of the consent process. This article discusses the results of a re-audit and aims to determine if this change in practice had resulted in any significant improvement in documentation. The consent forms of 100 consecutive patients undergoing primary total hip replacement were re-audited using a standardized data collection sheet in order to close the audit loop. The re-audit found that 86 consent forms used the procedure-specific complication sticker to list the potential complications associated with a total hip replacement. Statistically significant improvements in the documentation of fracture, neurovascular damage, leg length discrepancy, failure, premature loosening, death, medical complications, ongoing pain, stiffness, wound healing problems and other were all seen in the 2012 re-audit in comparison to the 2009 audit (P<0.0001). The cheap and simple introduction of procedure-specific complication stickers in order to help surgeons document the process of informed consent has resulted in significant improvements in practice. In the context of patient-focused care and satisfaction in the NHS, it is vital that simple measures such as the introduction of procedure-specific complication stickers are embraced.

Evidence-based review for patients undergoing elective hip and knee replacement

The objective of this study was to evaluate the evidence for different interventions in the preoperative, perioperative and post-operative care for people undergoing elective total hip (THR) and knee (TKR) replacement surgery. A multidisciplinary working group comprising consumers, managers and clinicians from the areas of orthopaedics, rheumatology, aged care and rehabilitation evaluated randomized controlled trials (RCTs) and systematic reviews/meta-analyses concerning aspects of preoperative, perioperative and post-operative clinical care periods for THR/TKR through systematic searching of Medline, Embase, CENTRAL and the Cochrane Database of Systematic Reviews from May 2007 to April 2011. Multiple reviewers determined study eligibility and one or more members extracted primary study findings. The body of evidence were assessed and specific recommendations made according to NHMRC guidelines. Twenty-five aspects were identified for review. Recommendations for 16 of 25 areas of care were made: impact of waiting, multidisciplinary preparation, preoperative exercise, smoking cessation, interventions for comorbid conditions, predictors of outcome, clinical pathways, implementation of a blood management programme, antibiotic prophylaxis, regional anaesthesia and analgesia, use of a tourniquet in knee replacement, venous thromboembolism prophylaxis, early post-operative cryotherapy, early mobilization and continuous passive motion. In the post-operative period, study heterogeneity across all aspects of care precluded specific recommendations. There was a deficiency in the quality of the evidence supporting key aspects of the continuum of care for primary THR/TKR surgery. Consequently, recommendations were limited. Prioritization and funding for research into areas likely to impact clinical practice and patient outcomes after elective joint replacement surgery are the next important steps.

GRP-164 Rivaroxaban Versus Enoxaparin: Comparison of Outpatient Treatment Adherence in Clinical Practise

BackgroundRivaroxaban (Riv) is a selective, direct Factor Xa inhibitor indicated in the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery (HKRS). [1] It was...

Aspectos prácticos de la administración de rivaroxabán

Rivaroxaban is an oral highly selective direct factor Xa inhibitor. Rivaroxaban is currently approved for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery, for the treatment of deep vein thrombosis and pulmonary embolism and long-term secondary prevention of venous thromboembolism, and for stroke and systemic embolism prevention in patients with nonvalvular atrial fibrillation. Rivaroxaban has many advantages over vitamin K antagonists and this may facilitate its use in clinical practice. As a result, it is expected that new oral anticoagulants may change patient management strategies. On the other hand, rivaroxaban has some particularities that are necessary to know. The aim of this manuscript was to review the use of rivaroxaban not only in general population, but also in specific patients groups and clinical situations to achieve an optimal management with this drug in daily clinical practice.

Erythrocyte Transfusion

Erythrocyte Transfusion

Renal impairment after high-dose flucloxacillin and single-dose gentamicin prophylaxis in patients undergoing elective hip and knee replacement

Following advice from the Scottish Antimicrobial Prescribing Group, we switched our antibiotic prophylaxis for elective hip and knee replacement surgery from cefuroxime to flucloxacillin with single-dose gentamicin in order to reduce the incidence of Clostridium difficile associated diarrhoea (CDAD). A clinical impression that more patients subsequently developed acute kidney injury (AKI) led us to examine this possibility in more detail. We examined the incidence of AKI in 198 consecutive patients undergoing elective hip or knee surgery. These patients were given the following prophylactic antibiotics: cefuroxime (n = 48); then high-dose (HD) flucloxacillin (5-8 g) with single-dose gentamicin (n = 52); then low-dose (LD) flucloxacillin (3-4 g) with single-dose gentamicin (n = 46) and finally cefuroxime again (n = 52). Patients receiving HD flucloxacillin required more vasopressors during surgery (P = 0.02); otherwise, there were no statistically significant differences in pre- and peri-operative characteristics between the four groups. The proportion of patients with any form of AKI by RIFLE criteria was first cefuroxime (8%), HD flucloxacillin with gentamicin (52%), LD flucloxacillin with gentamicin (22%) and second cefuroxime (14%; P < 0.0001). Odds ratios for AKI derived from a multivariate logistic regression model, adjusted also for sex and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with the first cefuroxime group as a reference category were: HD flucloxacillin with gentamicin 14.53 (4.25-49.71); LD flucloxacillin with gentamicin 2.96 (0.81-10.81) and second cefuroxime 2.01 (0.52-7.73). Three patients required temporary haemodialysis. Biopsies in two of these showed acute tubulo-interstitial nephritis. All three patients belonged to the HD flucloxacillin with gentamicin group. None of the patients developed CDAD. We have shown an association between the prophylactic antibiotic regimen and subsequent development of AKI following primary hip and knee arthroplasty that appeared to be due to the use of HD flucloxacillin with single-dose gentamicin. We found no evidence to suggest that this association was confounded by any of the co-variates we measured.

A case report describing a suspected rivaroxaban hypersensitivity reaction in a surgical patient

Rivaroxaban is an oral anticoagulant, currently licensed for use as a venous thromboembolism (VTE) prophylaxis, and recommended by the National Institute for Clinical Excellence (NICE) for all patients undergoing elective hip and knee replacement surgery in the UK. We present the first case of a suspected hypersensitivity to rivaroxaban. A 57-year-old man with no previous allergies underwent an uncomplicated, elective partial knee replacement, after which he was prescribed a routine 2-week course of rivaroxaban 10 mg. He developed an allergic response requiring readmission for assessment and treatment 7 days post-operatively. We believe this to be the first published case of hypersensitivity associated with rivaroxaban. More research is needed to determine this association. At the same time, given the growing range and increasing use of anticoagulants, particular vigilance is required regarding potential side effects so that these may be managed quickly and effectively in the early stages.

Cluster Analysis Followed by Network Meta-Analysis to Compare Efficacy and Safety of Dabigatran, Rivaroxaban and Apixaban After Elective Total Knee and Hip Replacement Surgery

AbstractAbstract 3409The new oral anticoagulant (NOAC) regimens (dabigatran 150mg od (D150) and 220mg od (D220), rivaroxaban 10mg od (R10), and apixaban 2.5mg bid (A5) have shown equivalent or superior efficacy and safety vs enoxaparin regimens for prevention of venous thromboembolism (VTE) following elective total knee (TKR) or hip replacement (THR) surgery. Due to a lack of head to head trials a network meta-analysis (NMA) may give information on a comparison between NOACs.Studies comparing a NOAC with low-molecular-weight heparin for prevention of VTE following TKR and THR were included into the following set of analyses. First, a cluster analysis was performed to identify homogenous groups. Second, only homogeneous studies regarding each endpoint (VTE and VTE related death, major bleeding, and mortality) were included into a meta-analysis for each NOAC regimen. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each NOAC program versus the comparator. Third, these OR and 95% CI were used for the NMA comparing the 4 treatment regimens.First, cluster analysis identified duration of treatment (10+5 and 32+5 days) as the only measure for obtaining homogeneity of trials for every NOAC on every endpoint at 10+5 and 32+5 days (p>0.05) except for A5 and VTE over 10+5 days (analysis not performed). Third, the results of the NMA of the OR and 95% CI of the 4 NOAC regimens over 10+5 days were: D150 and D220 not different on any endpoint; D150 and D220 inferior to R10 for VTE (p<0.01, p<0.001); A5 trend for less major bleeding than R10 (p=0.0546); no differences for the other indirect comparisons. Results for 32+5 days were: D150 and D220 not different on any endpoint; D150 and D220 inferior to R10 VTE (p<0.001, p=0.0015) and to A5 for VTE (p<0.001, p<0001); R10 and A5 not different on VTE. Comparisons of major bleeding and mortality were not different.The lack of a standard definition of VTE and bleeding outcomes between and sometimes within the studies of the NOACs substantially reduce the number of homogenous studies for inclusion into the present NMA using cluster analysis. The differences may help doctors and patients to decide the optimal treatment regimen for individual patient groups. Disclosures:No relevant conflicts of interest to declare.

Rivaroxaban for Thromboprophylaxis After Total Hip or Knee Replacement Surgery: Comparison of Outcomes of the XAMOS and RECORD Studies

AbstractAbstract 500Rivaroxaban for Thromboprophylaxis after Total Hip or Knee Replacement Surgery: Comparison of Outcomes of the XAMOS and RECORD Studies.Patients undergoing major orthopedic surgery are at risk of venous thromboembolism (VTE). Rivaroxaban has been approved for clinical use in this indication based on the extensive phase III RECORD program, which investigated the efficacy and safety of oral rivaroxaban regimens compared with subcutaneous enoxaparin regimens in patients undergoing elective total hip or knee replacement surgery. XAMOS is a phase IV, non-interventional, open-label cohort study that compared rivaroxaban with any pharmacological prophylaxis used in routine clinical practice for VTE prevention after major orthopedic surgery of the hip or knee. An additional aim of the XAMOS study was to assess whether the results from the phase III RECORD studies would be reflected in routine clinical practice.The XAMOS study, which ran from 2009 to 2011, collected data on the incidence of adverse events (including symptomatic thromboembolic and bleeding events) in adult patients from 252 centers in 37 countries worldwide, who underwent elective hip or knee replacement surgery (or hip fracture surgery, where appropriate) and received rivaroxaban or other pharmacological prophylaxis (standard of care). The attending physician determined the type, duration, and dose of drug. Of the 17,701 patients enrolled, 8778 received rivaroxaban and 8635 received standard of care, of whom 7055 (81.7%) received low molecular weight heparin (LMWH). Primary hip/knee replacement surgery accounted for >90% of all procedures. Baseline demographics (e.g. age, sex, body weight, and ethnicity) were similar for patients receiving rivaroxaban, standard of care, or LMWH, and were also similar to those of patients who received rivaroxaban in the RECORD program.LMWH was the comparator in the RECORD program; therefore, the XAMOS study also compared outcomes with LMWH and rivaroxaban. Data for the LMWH group were similar to the standard-of-care group. Rates of symptomatic arterial, venous, and all thromboembolic events in XAMOS were lower in the rivaroxaban group compared with the LMWH group (Figure 1). The data are consistent with the results of the RECORD1–4 pooled analysis, which showed a significantly lower incidence of symptomatic VTE and all-cause mortality in patients receiving rivaroxaban compared with those receiving enoxaparin (Figure 2). The rates of treatment-emergent major bleeding events (RECORD definition) were 0.4% vs 0.3% in the rivaroxaban and LMWH groups, respectively (odds ratio [OR]=1.28; 95% confidence interval [CI] 0.75–2.18; Figures 1 and 2), and were similar to those in the RECORD1–4 pooled analysis (day 12±2 active treatment pool: 0.3% [rivaroxaban] vs 0.2% [enoxaparin]; OR=1.62; 95% CI 0.77–3.53; Figure 2). When the European Medicines Agency (EMA) definition for treatment-emergent major bleeding was used, the incidence of major bleeding was slightly higher (nonsignificant) for patients receiving rivaroxaban compared with those receiving LMWH in the XAMOS study (1.7% vs 1.4%; OR=1.19; 95% CI: 0.92–1.53; Figures 1 and 2); these results were also similar to those of the RECORD1–4 pooled analysis (day 12±2 active treatment pool: 2.0% [rivaroxaban] vs 1.7% [enoxaparin]; OR=1.20; 95% CI: 0.91–1.57).XAMOS is the first study presenting real-world experience of the efficacy and safety of rivaroxaban for the prevention of VTE after major orthopedic surgery of the hip or knee. The results of XAMOS showed that rivaroxaban was associated with a significantly lower incidence of symptomatic VTE compared with LMWH, without a significant increase in the risk of major bleeding. These findings are consistent with those obtained in the RECORD studies, and indicate that the results of the RECORD program can be translated into the routine clinical setting. [Display omitted] [Display omitted] Disclosures:Turpie:GSK: Speakers Bureau; GSK, JnJ: Consultancy. Schmidt:Bayer: Employment, Equity Ownership. Lassen:Bayer: Speakers Bureau; Bristol-Myers Squibb; GlaxoSmithKline; Bayer; Boehringer: Consultancy; Sanofi-Aventis: Research Funding. Mantovani:Bayer Healthcare Pfizer Merck Serono Baxter Astellas: Speakers Bureau; Bayer Healthcare Pfizer Bristol-Meyer Squibb Amgen Merck&Co: Consultancy; Bayer Healthcare Pfizer Bristol-Meyer Squibb Biogen Idec Medtronic Admirall Otsuka Amgen Merck&Co Merck-Serono: Research Funding. Kreutz:Bristol-Myers Squibb, Bayerm Daichii Sankyo, Berlin-Chemie Menarini: Speakers Bureau; Bayer, Daichii Sankyo: financial and material support, financial and material support Other. Holberg:Bayer Healthcare: Employment. Haas:Sanofi Aventis: Speakers Bureau; Sanofi Aventis, Bristol-Myers Squibb: Consultancy.

Determination of Rivaroxaban in Urine Samples From Patients Undergoing Elective Hip- and Knee Replacement Surgery Using a Point of Care Method

AbstractAbstract 1162Rivaroxaban is approved at fixed dose for several indications to prevent thromboembolism. Despite the lack of need to dose adjust rivaroxaban it may be necessary to determine its activity/concentration in specific patient populations. Several assays are available to determine the anticoagulant in plasma samples. A point of care (POC) method may provide immediate results for patients requiring acute medical interventions and facilitate therapeutic decisions.Plasma and urine samples were taken from patients (n=150) after having given written informed consent before and between days 4 to 6 following primary elective total knee (THR) and hip replacement (THR) surgery on antithrombotic therapy with 10mg rivaroxaban od. For laboratory assays, rivaroxaban was purified from commercially available Xarelto®. The compound was characterized by analytical methods and was quantified in plasma samples using the factor Xa specific S2222 chromogenic substrate assay as described (J Thromb Haemost 2012,10:1433–6). In urine rivaroxaban was determined by a POC method incubating the lyophilized reagents on mini-strips followed by incubation with patient‘s urine (patent No GB1019674.9). The development of colour of urine samples 10 min after incubation with reagents was determined quantitatively by optical density (OD) measurement and judged by eye qualitatively according negative and positive colour (three independent readings by SD, SK, CG, and photographic documentation). To determine the positive and negative predictive value (PPV, NPV) of plasma samples, a cutoff value of <25 ng/ml rivaroxaban was defined. The PPV and NPV of the POC method with urine samples were determined according to positive and negative results of colour development judged by eye reading.Before administration of rivaroxaban 127/144 patients displayed plasma concentrations of 11.1+7.1 ng/ml (mean, standard deviation) and 17 patients a concentrations of 40.4+13.1 ng/ml (cut off value >25ng/ml). The NPV was 88.2%. During therapy the concentration of rivaroxaban was 76.7+36.6 ng/ml in 113/135 patients (above cutoff value) and 14.3+5.2 ng/ml in 22/135 patients (below cutoff value). The PPV was 83.7%. Values were negative in 16.3% of these patients. Using the POC method for rivaroxaban in urine all of 117 patients had negative values with OD measurement (1.23+0.14 OD units) and eye measurement. The NPV was 100%. During therapy with rivaroxaban 4/125 patients had negative colour development by eye measurement with an OD of 1.21+0.02. 121/125 showed colour development as judged by eye corresponding to an OD of 0.16+0.09. The PPV was 96.8%. There was no interobserver variability. Limitation of the methods is the lack of sure information about the compliance of the patients. Further validation of the POC method is ongoing.Under real life conditions the POC method and judgement of colour development by eye increased the PPV and NPV from about 85% using plasma samples to more than 95% using urine samples for determination of rivaroxaban. The method is non-invasive, rapid, and specific, can be repeatedly performed and may be used by medical personal and patients. Colour development differs from the POC method for dabigatran from urine samples of patients on treatment. Disclosures:No relevant conflicts of interest to declare.

Hospital discharge information after elective total hip or knee joint replacement surgery: a clinical audit of preferences among general practitioners

The demand for elective joint replacement (EJR) surgery for degenerative joint disease continues to rise in Australia, and relative to earlier practices, patients are discharged back to the care of their general practitioner (GP) and other community-based providers after a shorter hospital stay and potentially greater post-operative acuity. In order to coordinate safe and effective post-operative care, GPs rely on accurate, timely and clinically-informative information from hospitals when their patients are discharged. The aim of this project was to undertake an audit with GPs regarding their preferences about the components of information provided in discharge summaries for patients undergoing EJR surgery for the hip or knee.GPs in a defined catchment area were invited to respond to an online audit instrument, developed by an interdisciplinary group of clinicians with knowledge of orthopaedic surgery practices. The 15-item instrument required respondents to rank the importance of components of discharge information developed by the clinician working group, using a three-point rating scale.Fifty-three GPs and nine GP registrars responded to the audit invitation (11.0% response rate). All discharge information options were ranked as 'essential' by a proportion of respondents, ranging from 14.8-88.5%. Essential information requested by the respondents included early post-operative actions required by the GP, medications prescribed, post-operative complications encountered and noting of any allergies. Non-essential information related to the prosthesis used. The provision of clinical guidelines was largely rated as 'useful' information (47.5-56.7%).GPs require a range of clinical information to safely and effectively care for their patients after discharge from hospital for EJR surgery. Implementation of changes to processes used to create discharge summaries will require engagement and collaboration between clinical staff, hospital administrators and information technology staff, supported in parallel by education provided to junior medical staff.