Major Joint Replacement Surgery Research Articles

Adrenal haemorrhage due to heparin-induced thrombocytopenia

Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had "spontaneous HIT" with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement.

Polysaccharide hemostatic system reduces blood loss in high-body-mass-index patients undergoing simultaneous bilateral total knee arthroplasty

BackgroundTo investigate the efficacy of a topically applied hemostatic agent used to reduce blood loss in patients undergoing simultaneous bilateral total knee arthroplasty (TKA). MethodsThirty-two patients (5 male, 27 female) mean age 65 ± 9.3 (46–80) undergoing single-stage bilateral TKA were enrolled in the study and divided in two groups. Groups 1 and 2 consisted of patients with body mass index (BMI) <30 and >30, respectively. Polysaccharide hemostatic agent (PHA; 3g) was applied topically to the right knees of each patient intraoperatively. The left knees were used as controls. A negative suction drain was used and the effect of PHA and BMI on postoperative bleeding was evaluated. ResultsBlood loss was significantly higher (p = 0.027, r = 0.397) for patients with higher BMI. Treatment by local application of PHA to potential bleeding sites significantly reduced blood loss—314 ± 151ml (50–600) for the right knees versus 468 ± 140ml (150-700) for the left knees (p = 0.007) in group 1; 420 ± 251 ml (100–900) for the right knees versus 620 ± 229ml (350–1125) for the left knees (p = 0.036) in group 2. Blood loss reduction between the right and left knees was no different between the two groups (p = 0.173). ConclusionsBy reducing blood loss and the need for postoperative blood transfusion in patients with high BMI, PHA can be of value as adjuvant therapy in new blood-management procedures in major joint-replacement surgery.

A New Generation of Oral Direct Anticoagulants

After more than 50 years of thrombosis treatment and prophylaxis being based on heparin and vitamin K antagonists, a new generation of oral, direct anticoagulants is now available. The past 5 years have brought a strikingly large number of trials that evaluated these new oral anticoagulants in a range of clinical trials, particularly nonvalvular atrial fibrillation, thrombosis prophylaxis after major joint replacement surgery, treatment of venous thromboembolic events, and, most recently, acute coronary syndrome. These studies have been notably similar in design between the drugs for specific indication. This review focuses on the 3 drugs that either have recently been approved by the US Food and Drug Administration (dabigatran and rivaroxaban) or have the most mature phase III clinical data (apixaban).

Disparities in Major Joint Replacement Surgery among Adults with Medicare Supplement Insurance

The objective of this study was to determine if disparities in hip and knee replacement surgery exist among osteoarthritis patients with AARP-branded Medicare supplement plan (ie, Medigap) coverage provided by UnitedHealthcare. Patients were selected into the study if they had 1 or more medical claims with a diagnosis of osteoarthritis from July 1, 2006 to June 30, 2007. Logistic regression analyses tested for age-, sex-, race-, or income-related differences in the likelihood of receiving a hip or knee replacement surgery. The regression models controlled for socioeconomics, health status, type of supplement plan, and residential location. Of the 2.2 million Medigap insureds eligible for this study, 529,652 (24%) had osteoarthritis. Of these, 32,527 (6.1%) received a hip or knee replacement. Males were 6% (P < 0.001) more likely than females to have a replacement surgery. Patients living in minority or lower income neighborhoods were less likely to receive a hip or knee replacement. Supplement plan type was not a strong predictor of the likelihood of hip or knee replacement. Disparities were much greater by comorbid condition and residential location. Disparities in hip and knee replacement surgery existed by age, sex, race, and income levels. Larger disparities were found by residential location and comorbid condition. Interventions are being considered to address these disparities.

Does Manipulating Local Surgical Wound Cytokines Improve Surgical Outcomes?

Surgical trauma produces complex local biochemical changes that contribute to inflammation and acute postoperative pain, and in some cases to chronic pain.1 Tissue injury induces an increase in the complex cascade of inflammatory cytokines that can induce peripheral and central nervous system sensitization, leading to hyperalgesia.2 In a set of articles in this issue of the journal, Hu et al.3,4 describe the role of one of these inflammatory cytokines, interleukin (IL)-1β, in postsurgical wound healing and acute postoperative pain. In a rodent model of incision pain, they demonstrated that the antiinflammatory cytokine, IL1ra, which antagonizes the binding of IL-1β to its receptor, decreases postoperative mechanical hypersensitivity when administered intraperitoneally. In addition, the concentration of other inflammatory cytokines, such as IL-6 and tumor necrosis factor (TNF)α, were reduced in wound skin tissue. This complements their human studies, which showed that IL-1β stimulated cytokine production, especially IL-8, in vitro in primary human keratinocytes, and that IL-1β and IL-8 levels were highly correlated in surgical wound exudates from both cesarean incisions and sunburn-induced blisters. The authors suggest that because a commercially available recombinant version of IL1ra, anakinra, is already in use in rheumatoid arthritis patients, a clinical trial to assess its value in improving wound healing and reducing pain when administered perioperatively can be considered. What are the main issues to consider before using any type of cytokine modulator to reduce inflammation and pain during the perioperative period? First, how serious a problem is wound healing and acute postoperative pain for each type of surgery being considered? Second, are some of the inflammatory immune mediators necessary as part of the normal defense of the surgical wound to prevent infection? With small incisions of skin and underlying muscle with minimal retraction, postoperative outcomes are usually good and recovery is uneventful. Therefore, cytokine manipulation may not be needed. However, for major types of surgery, e.g., joint replacement surgery, spine, or thoracotomy, acute postoperative pain may be severe and can delay rehabilitation. In addition, with procedures such as knee replacement surgery and thoracotomy, the incidence of persistent postsurgical pain is relatively high5; therefore, there are even more incentives to consider reducing postsurgical inflammation.1 The relative importance of each cytokine may differ depending on the type of surgery. With hip replacement surgery, concentrations of IL-1β, IL-6, and IL-8 increase in hip drain exudates, whereas TNFα levels decrease.6 Similarly, as described in this issue of the journal, in cesarean delivery, local inflammatory mediators such as substance P, IL-1, IL-6, IL-8, and IL-10 are increased.7 However, it is not known whether controlling surgical site IL-1β release or binding would be more important than suppressing IL-6 or IL-8 in improving wound healing and reducing pain. In the earlier stages of wound healing (up to 24 hours), neutrophils are the dominant cell type in the local immune response,8–10 and after hip replacement surgery, there is upregulation of gene expression for such inflammatory modulators as macrophage migration inhibitory factor, IL1ra itself, the chemokine CCL20, and receptors for IL-8 and IL-18 in neutrophils extracted from the wound drainage.11 Recent basic12 and clinical studies13 all point to IL-1 as the main local tissue receptor type correlated with postoperative analgesia. Choosing the correct dose of the IL-1 receptor blocker, anakinra, for a clinical trial affecting surgical outcomes may not be obvious, based on approved doses for rheumatoid arthritis. In the rodent incision model, the anakinra dose to reduce postoperative mechanical hypersensitivity was 100 mg/kg. However, the daily dose in rheumatoid arthritis patients is 100 mg,4,12 which is approximately 1 mg/kg. Whereas the antihyperalgesic doses in rodent pain models are often much larger than doses used clinically to reduce pain, it is possible that the maximum approved anakinra dose for patients may be inadequate to decrease postoperative pain. In a review of clinical trials using anakinra for chronic rheumatoid arthritis, the incidence of serious infections was 1.8% in the anakinra group versus 0.6% in the placebo group.14 Although for cutaneous wounds this may not be a real clinical issue, for major joint replacement surgery, an infected prosthesis could be detrimental. All of the above issues apply not just to anakinra, but to inflammatory cytokine modulators in general (e.g., TNFα inhibitors: etanercept, adalimumab, infliximab). The 2 articles in this journal,3,4 along with previous animal studies,15,16 provide a rationale for IL1ra administration in the perioperative setting. Nevertheless, it is important that the choice of surgery for an initial clinical trial is chosen judiciously. A key consideration is that the surgery in question be one in which surgical outcomes have a relatively high incidence of acute pain, and possibly chronic pain, so that a successful treatment will be clinically and statistically significant. In addition, the type of surgery chosen for study should be one in which infection would be relatively easy to treat, should one occur.

Effect of Very Dose Warfarin therapy Upon the Markers of Activcation of Clotting Following Major Joint Replacement Surgery

AbstractAbstract 4395Prophylaxis against post-operative deep vein thrombosis using low dose warfarin is appealing as it is inexpensive and with low risk of hemorrhage. Investigators have examined this issue with variable outcomes. Critical to our thinking is that the drug must be started prior to the elective surgical intervention in order to be an effective antithrombotic agent, while not causing potential hemorrhagic anticoagulation. This abstract describes the effect of such a regimen on the generation of markers of coagulation activation, comparing fixed very low dose warfarin (1 mg daily) to variable dose warfarin among patients having elective replacement of hip or knee surgery. The fixed low dose warfarin is begun 7 days prior to surgery and continued 28 days post operatively. Variable dose warfarin is begun at 5 mg the night prior to surgery and is continued for 28 days post operatively with the target INR 2.0–2.5, adjusted twice per week. For this study the markers of coagulation activation are prothrombin fragment F1+2 and thrombin-anti-thrombin complex (T-AT). They are measured prior to start of warfarin therapy (baseline), on the morning of surgery (OR Day), and on postoperative days 3 and 28. PIVKA II is measured at the same time points as a measure of warfarin activity other than the INR. For this study 10 patients for each group are taken from a larger group of patients participating in a randomized prospective study of this regimen now in progress. Both studies are IRB approved. Table 1 demonstrates the results.BaselineOR DayPost-op day 3Post-op day 28F1+2Fixed dosemean221223.5441.8341.8pmol/L(±1 SD)(108.1)(101.7)(154.1)(152.5)(normal: 87-325)Variable dosemean261.2213.3308.1112.2(±1 SD)(61.4)(57)(126.3)(56.3)T-ATFixed dosemean2.62.410.63.6ng/ml(±1SD)(0.9)(0.8)(3.8)(1)(normal: <5.1)Variable dosemean2.72.910.92.9(±1SD)(1.2)(2.7)(7.6)(0.7)PIVKA-IIFixed dosemean2.78.542.311.9ng/ml(±1SD)(2.4)(6.0)(38.7)(13.2)(normal: <3.6)Variable dosemean2.36.9427.91250.5(±1SD)(0.8)(8.8)(599.3)(833.7)As expected the PIVKA II is increased over normal for both groups by OR Day and on post-operative days 3 and 28. Greater increases in PIVKA II, as expected, occur among patients receiving variable dose warfarin, as this group received higher doses. The T-AT is elevated by post-operative day 3 and is returned to normal on post-operative day 28 in both groups. At each time point the T-AT values are equal for the two study groups. The F1+2 values are modestly increased for both groups on post-operative day 3, with better suppression of F1+2 generation by the variable dose regimen on day 28. In conclusion, the fixed low dose warfarin regimen is as effective as the variable dose warfarin as measured by the generation of T-AT, and is possibly somewhat less effective as determined by the generation of F1+2. The clinical significance of this difference is unknown, especially given the suppression of the T-AT. None of these patients suffered postoperative thromboembolic disease. Disclosures:Adcock:Esoterix Laboratory Services, Inc: Employment.

Major elective joint replacement surgery: socioeconomic variations in surgical risk, postoperative morbidity and length of stay

Patient deprivation is associated with greater need for total hip and knee replacement surgery (THR/TKR) and a higher prevalence of risk factors for surgical complications. Our aim was to examine associations between deprivation and aspects of the inpatient episode for patients undergoing these procedures. We analysed socioeconomic variations in preoperative surgical risk, postoperative morbidity and length of stay for 655 patients undergoing elective THR/TKR at a large metropolitan hospital. Surgical risk was assessed using the orthopaedic version of the POSSUM scoring system, postoperative morbidity was assessed using the postoperative morbidity survey, and socioeconomic status was measured using the Index of Multiple Deprivation. We adjusted for age, sex, surgical site and primary vs. revision surgery. We found only a modest, clinically insignificant socioeconomic gradient in preoperative surgical risk and no socioeconomic gradient in postoperative morbidity. There was a strong socioeconomic gradient in length of stay, but only for patients undergoing TKR. This was due to deprived patients being more likely to remain in hospital without morbidity following TKR. Our findings suggest differential selection of healthier patients for surgery. Hospitals serving deprived communities may have excess, unfunded costs because of the increased length of stay of socioeconomically disadvantaged patients.

Dabigatran Etexilate for the Prophylaxis of Venous Thromboembolism After Hip or Knee Replacement Rationale for Dose Regimen

Dabigatran etexilate is an oral reversible direct thrombin inhibitor that offers potential practical advantages over existing anticoagulants for the prevention of venous thromboembolism after major joint replacement surgery. These include oral administration, rapid onset of action, and a predictable anticoagulant effect that obviates the need for laboratory monitoring. Evidence from 3 phase II dose-finding trials showed that dabigatran etexilate, 100 to 300 mg daily, had similar efficacy, risk of bleeding, and tolerability compared with enoxaparin. Using pharmacokinetic modeling and taking into account efficacy/safety considerations, dabigatran etexilate 150 mg and 220 mg once daily, with a half-dose on the day of surgery, were selected for further evaluation in phase III trials. These doses were selected to ensure that the risk of bleeding did not exceed that of enoxaparin. This review discusses the rationale for selection of these dose regimens based on results from phase II trials.

Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to Surgery

Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to SurgeryDespite many achievements during the last decade, postoperative pain remains the dominant complaint after major surgery and has great potential to be influenced by the anaesthesiologist. Reports suggest that short-term effective anaesthesia and analgesia can have long-lasting beneficial effects on recovery from surgery. The aim of our study is to compare the effect of epidural analgesia, using different compositions, including glucocorticoids (methylprednisolone), and habitual composition of bupivacaine-morphine, in regard to analgesic and anti-inflammatory properties. A total of 129 patients participated in the study in four different treatment groups: patients from Group I received glucocorticoid methylprednisolone succinate and long-acting opioid morphine hydrochloride, Group II received local anaesthetic bupivacaine hydrochloride and morphine hydrochloride, Group III received methylprednisolone succinate and short-acting opioid fentanyl, and Group IV received glucocorticoid methylprednisolone succinate. We obtained good analgesic profiles in all groups. However, significantly better results were achieved using the combination of methylprednisolone and morphine. Epidural methylprednisolone in dose 80 mg/24 h is more effective, compared to the conventional local anaesthetics-opioid composition, when administered as a part of multimodal preventive postoperative analgesia after major joint replacement surgery. Epidural methylprednisolone has a reliable anti-inflammatory and immunomodulatory potential. It attenuates profiles of acute inflammatory response markers as Interleukin-6 and C-reactive protein and stress hormone cortisol. The novelty of this study was application of epidural glucocorticoids for acute postoperative pain relief as part of daily perioperative care. By developing studies on anti-inflammatory and immunomodulatory properties of glucocorticoids, we expect to improve patient rehabilitation in the postoperative period.

Should an asymptomatic patient with an abnormal urinalysis (bacteriuria or pyuria) be treated with antibiotics prior to major joint replacement surgery?

Should an asymptomatic patient with an abnormal urinalysis (bacteriuria or pyuria) be treated with antibiotics prior to major joint replacement surgery?

Critical Care Issues in the Patient After Major Joint Replacement

Admission rates of orthopedic patients to intensive care units are increasing. Thus, an intensivist's familiarity with specific problems associated with major joint replacement surgery is of utmost importance in order to meet the needs of this particular patient population. In this article, the authors review the most commonly encountered complications after major hip and knee arthroplasty. Perioperative risk factors for morbidity and mortality and the epidemiology, diagnosis, and treatment of cardiopulmonary complications in this patient population are discussed. Procedure-specific complications such as fat embolism and acrylic bone cement-related issues are reviewed.

Routine anaesthesia for joint replacement surgery

Although now routine, major joint replacement surgery of both the upper and the lower limb represents a challenge to anaesthetists because of the relatively elderly age group of patients, their attendant co-morbidity and the complexity of the surgery. Preoperative assessment and optimization of each patient's medical condition is important for a successful outcome of surgery, which can be prolonged with significant perioperative blood loss. Surgery is associated with high pain intensity in the early postoperative period, and effective analgesia (whether based on systemic opioids or regional analgesia) is necessary for up to 24 hours before patients can mobilize comfortably, with mild to moderate levels of pain. Joint revision surgery is now common when primary joint replacements reach the end of their expected lifespan. Revision surgery introduces additional complexity and increases perioperative morbidity and the duration of surgery, making anaesthesia for such operations difficult. Both general and regional anaesthesia techniques are in widespread use. General anaesthesia and a local anaesthetic block for optimal perioperative analgesia is recommended for shoulder, elbow and knee replacements, whilst spinals and epidurals may be used as either the sole technique or in combination with a light general anaesthetic for hip replacement. There is evidence that central neural blockade is associated with a reduction in morbidity and mortality for lower limb joint replacement, and that functional outcome may be improved for both upper and lower limb surgery if a regional block technique is used to provide postoperative analgesia.

MRSA-free elective orthopaedic surgery.A dedicated elective orthopaedic ward free from MRSA Alexandra Hospital, Redditch, UK.

Deep infection complicating arthroplasty surgery carries a heavy financial and emotional burden on any orthopaedic service. The cost of hospital acquired infection is estimated at 1 billion per year by the National Audit Office. Healthcare associated infection is an area currently under great scrutiny. The Alexandra Hospital, Redditch, has developed a dedicated elective orthopaedic ward free from methicillin-resistant Staphylococcus aureus (MRSA) that delivers high quality and high volume major joint replacement surgery through rigorous infection control. Between October 2001 and December 2002, the Alexandra Hospital had an infection rate of 0.21% for total knee replacements compared to the national rate of 2.1% p= 0.002 (CI 0.00005-0.01) The infection rate for total hip replacements was 1.31% compared to 3.8% nationwide. p= 0.01 (CI 0.004- 0.03). The total number of joint replacements performed per year, utilising the same number of elective beds, increased from 482 in 2001 to 629 in 2002. We believe that the MRSA screening policy and subsequent altered bed utilisation have contributed to lowering the rate of infection and improved efficiency. We have developed a safe, effective and efficient orthopaedic unit within the framework of an acute NHS trust. We believe the practical changes and modest investment that have been made within our department can be repeated in other units around the country with relative ease. (Hip International 2005; 15: 171-6).

MRSA-free elective orthopaedic surgery.A dedicated elective orthopaedic ward free from MRSA Alexandra Hospital, Redditch, UK

Deep infection complicating arthroplasty surgery carries a heavy financial and emotional burden on any orthopaedic service. The cost of hospital acquired infection is estimated at 1 billion per year by the National Audit Office. Healthcare associated infection is an area currently under great scrutiny. The Alexandra Hospital, Redditch, has developed a dedicated elective orthopaedic ward free from methicillin-resistant Staphylococcus aureus (MRSA) that delivers high quality and high volume major joint replacement surgery through rigorous infection control. Between October 2001 and December 2002, the Alexandra Hospital had an infection rate of 0.21% for total knee replacements compared to the national rate of 2.1% p= 0.002 (CI 0.00005-0.01) The infection rate for total hip replacements was 1.31% compared to 3.8% nationwide. p= 0.01 (CI 0.004- 0.03). The total number of joint replacements performed per year, utilising the same number of elective beds, increased from 482 in 2001 to 629 in 2002. We believe that the MRSA screening policy and subsequent altered bed utilisation have contributed to lowering the rate of infection and improved efficiency. We have developed a safe, effective and efficient orthopaedic unit within the framework of an acute NHS trust. We believe the practical changes and modest investment that have been made within our department can be repeated in other units around the country with relative ease. (Hip International 2005; 15: 171-6).

Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery

As continuous wound instillation with local anaesthetic has not been evaluated after hip/knee arthroplasties, our study was designed to determine whether this technique could enhance analgesia and improve patient outcome after joint replacement surgery. Thirty-seven patients undergoing elective hip/knee arthroplasties under spinal block were randomly assigned to two analgesia groups. Group M received continuous i.v. infusion of morphine plus ketorolac for 24 h. Then, a multi-hole 16 G catheter was placed subcutaneously and infusion of saline was maintained for 55 h. Group R received i.v. saline. Thereafter the wound was infiltrated with a solution of ropivacaine 0.5% 40 ml, then a multi-hole 16 G catheter was placed subcutaneously and an infusion of ropivacaine 0.2% 5 ml h(-1) was maintained for 55 h. Visual analogue scale scores were assessed at rest and on passive mobilization by nurses blinded to analgesic treatment. Total plasma ropivacaine concentration was measured. Group R showed a significant reduction in postoperative pain at rest and on mobilization, while rescue medication requirements were greater in Group M. Total ropivacaine plasma concentration remained below toxic concentrations and no adverse effects occurred. Length of hospital stay was shorter in Group R. Infiltration and wound instillation with ropivacaine 0.2% is more effective in controlling postoperative pain than systemic analgesia after major joint replacement surgery.

Ximelagatran and melagatran compared with dalteparin for prevention of venous thromboembolism after total hip or knee replacement: the METHRO II randomised trial

Heparins substantially reduce the risk of thromboembolic complications after total hip or knee replacement. However, they can be given only by injection and have several other drawbacks. We did a multicentre, randomised, double-blind study to examine the dose-response relation of subcutaneous melagatran, a direct thrombin inhibitor, followed by oral ximelagatran as thromboprophylaxis after total hip or knee replacement. We aimed to compare the efficacy and safety with that of dalteparin. Of 1900 patients, 1495 were assigned to four dose categories of subcutaneous melagatran from just before surgery (1.00 mg, 1.50 mg, 2.25 mg, or 3.00 mg twice daily) followed from the day after surgery by oral ximelagatran (8 mg, 12 mg, 18 mg, or 24 mg twice daily). 381 patients were assigned subcutaneous dalteparin 5000 IU once daily, from the evening before surgery. Bilateral venography was done at 7-10 days, and clinically suspected venous thromboembolism (VTE) was confirmed radiologically. The primary endpoint was the rate of deep-vein thrombosis and pulmonary embolism (PE). Analyses were by intention to treat. 1876 patients underwent total replacement of hip (n=1270) or knee (n=606); evaluable venograms were obtained in 1473 (79%). Four patients without evaluable venograms had PE. Overall, a significant dose-dependent decrease in VTE was seen with melagatran/ximelagatran (lowest to highest group: 111 [37.8%], 70 [24.1%], 71 [23.7%], and 43 [15.1%]; p=0.0001); there were also significant relations for both total hip and total knee replacement individually. The frequency of VTE was significantly lower with the highest dose of melagatran/ximelagatran than with dalteparin (15.1% vs 28.2%, p<0.0001). There were no reoperations due to bleeding and no critical organ bleeding. Excessive surgical bleeding was uncommon but more frequent in the highest dose group. This sequential therapy was effective and safe in patients undergoing major joint replacement surgery. The findings should be confirmed in a large phase III trial.

Perioperative Stroke Prevention

The definitions of commonly used terms are given in Table 1 (1–8). Stroke has been simply defined as any form of cerebral infarction (2), which includes those attributable to hemorrhage. The latter group is more likely to occur as a complication of specific surgical procedures (e.g., carotid endarterectomy) or the use of anticoagulants and is otherwise rare in the perioperative period (3). Hence, much of the information in this review pertains to ischemic cerebral events.

Peri‐operative silent myocardial ischaemia in patients undergoing lower limb joint replacement surgery: an indicator of postoperative morbidity or mortality?

One hundred and twenty-seven patients undergoing major lower limb joint replacement surgery were studied to determine the incidence of silent myocardial ischemia and to ascertain any link between pre-operative cardiac risk factors, silent myocardial ischaemia and postoperative morbidity. Patients underwent ambulatory ECG monitoring for 4 days (on the pre-operative night and for 3 days postoperatively). Postoperative cardiorespiratory symptomatology and morbidity was assessed by questionnaire at 3 months. Eighty-seven patients had risk factors for silent myocardial ischaemia; 42 patients (30 with risk factors) had peri-operative silent myocardial ischaemia. The median ischaemic loads (range) were 1.04 (0.32-13.31) min.h-1 pre-operatively and 5.53 (0.26-56.39), 6.69 (0.04-42.71) and 1.23 (0.1-53.74) min.h-1 on postoperative days 1-3, respectively. Risk factors did not predict the occurrence of silent myocardial ischaemia or an increased ischaemic load pre-operatively or overall postoperatively. New symptoms (chest pain, palpitations, breathlessness or fatigue) were associated with both silent myocardial ischaemia and ischaemic load (p < 0.05). Thus cardiac risk factors do not predict the occurrence of silent myocardial ischaemia or adverse outcome. Peri-operative silent myocardial ischaemia was associated with increased postoperative fatigue.

Mechanisms of Hypercoagulability

Following certain major operative procedures, large amounts of tissue factor may be released from damaged tissues to venous blood. Mechanical and chemical injury to the collecting veins exposes subendothelial procoagulant proteins. This initiates a marked local hypercoagulable process. Subsequently, venous bloodborne procoagulant debris induce a substantial thrombin generation as blood passes the lung capillaries. Thus, the lungs seem to have a central role in the mechanisms of hypercoagulability in high-risk patients. Hypercoagulable blood is squeezed out in the peripheral circulation and may favor thrombosis formation both in central and peripheral vessels. In addition, reduced venous blood flow for several days to weeks after the operation may put these patients at-risk for thromboembolic complications for a long time. Several predisposing genetic and acquired factors associated with thrombophilia have been proposed to contribute to this hypercoagulable process. However, few studies and conflicting results have been reported. The clinical penetrance of the described thrombophilic abnormalities and their contribution to the hypercoagulable process in "high-risk" patients are, at present, unclear. The post-traumatic hypercoagulability seems to be a systemic phenomenon, at least following major orthopedic surgery. Cardiorespiratory and vascular complications play a prominent role as a cause of death and morbidity during and after this kind of surgery.