Title: Safety and Feasibility Evaluation of Tourniquets for Total Knee Replacement (SAFE-TKR) Study
Funder: Department of Health and Social Care

Abstract: This is a study designed to determine if a full randomised controlled trial comparing clinical outcomes following TKR surgery with or without a tourniquet is feasible. One of the most important clinical outcomes for evaluation in a full RCT is the presence of cognitive impairment secondary to cerebral emboli. However, other outcomes also need evaluation including venous thromboembolism, knee pain and function and general health related quality of life and rates of revision surgery. It is not clear whether informed patients would agree to take part in such a trial and whether surgeons would agree to recruit and randomise their patients. A feasibility study will be conducted including: A pilot randomised controlled trial. Patients undergoing TKR surgery in one hospital (University Hospital Coventry and Warwickshire UHCW) will be invited to take part and randomly allocated to one of the two trial treatments (surgery with or surgery without a tourniquet). All patients will have a Magnetic Resonance (MR) imaging brain scan preoperatively and 2 days postoperatively to look for evidence of cerebral emboli which may be related to TKR surgery. The Oxford Cognitive Screen, Montreal Cognitive Assessment and Mini-Mental State Examination will be evaluated as potential primary outcome tools for measuring symptomatic cerebral emboli in a full trial. Other potential primary clinical outcomes will be collected and evaluated including: symptomatic VTE, revision rates up to 12 months and Oxford Hip Scores and EQ-5D-5L Scores at 6 and 12 months. The pilot trial will seek to recruit and analyse MR and cognitive function data at 2 days post-surgery for 50 patients. An integrated qualitative research study. A purposive sample of around 30 patients (split between those who agree and those who do not agree to take part in the pilot trial) and around 20 surgeons (nationally, with a mix of those that are likely to be in equipoise and those that are not) will be invited to take part in semi-structured interviews. UK based TKR surgeons will be identified through an initial national survey conducted through the British Association for Surgery of the Knee (BASK) and invited to interview. The analysis of the qualitative interview will be informed by a constant comparative approach to ensure early analysis informs subsequent data collection. The interviews will help capture the views amongst patients and surgeons about the pilot trial and explore the barriers and potential solutions to a full trial.A retrospective multi-centre cohort study. In the first year (2003) that prospective data for TKR surgery was collected as part of the National Joint Registry (NJR) for England and Wales details about the intraoperative use of a tourniquet was also collected. Up to 31December 2003 the NJR has data for 19,379 and 1,475 TKR procedures done with and without a tourniquet respectively. This NJR dataset will be linked to the NHS Personal Demographics Service, which provides dates of death and Hospital Episode Statistic (HES) for reported episodes of death and VTE. This will help estimate the relationship if any between tourniquet use and these other events. On completion, the feasibility study will have established whether patients and surgeons are prepared to participate in a full trial. Potential outcome measures for a full trial including measures of cognitive function will have been evaluated and tested ready for a full trial. At the end of the study key stakeholders (patients, surgeons, public representatives and researchers) will review the study results and using consensus conference methodology determine the final feasibility and most appropriate primary outcome measures for a full definitive trial.

Lay abstract: Total knee replacement (TKR) surgery is routinely undertaken for end stage arthritis of the knee. The majority of surgeons perform TKR surgery with the aid of a tourniquet, which is an inflatable device placed around a patient's thigh during the surgery. The tourniquet interrupts the blood supply and drainage from the leg and helps to create a bloodless field during the procedure. A tourniquet may however increase a patients' risk of developing a blood clot within the leg (Deep Vein Thrombosis DVT), or if the clot travels to the lungs a pulmonary embolism (PE). DVT and PE are collectively known as venous thromboembolism (VTE) and can cause leg swelling, pain, breathlessness, lung damage and in some cases sudden death. At the end of surgery the tourniquet is deflated and blood clots and other microscopic surgical debris that may have accumulated in the leg (such as cement and fat from the cut bone surfaces) are immediately free to flow (embolise) within the blood stream. In some cases blood clots and debris can return to the heart where they are then free to travel to the brain and cause brain damage (a stroke) and affect brain function. There may also be other less serious implications of using a tourniquet including effects on post-operative knee pain and function. The potentially increased risk of clots and debris in the brain associated with using a tourniquet has never been examined with any definitive randomised controlled trials (RCTs) and it is unclear if such a RCT would even be feasible. There may be problems with running a trial which involves recruiting patients who, once it is explained, may not be prepared to accept the potential risks of surgery with a tourniquet. Equally surgeons may be not willing to change surgical practice for a randomised trial. Also, although there are good imaging tests for detecting clots and debris within the brain, it is not clear if there are any good practical clinical tests of brain function (i.e. cognitive tests) for detecting the symptomatic brain damage arising from the presence of clots and debris. An initial feasibility study is therefore planned and will comprise three parts: Pilot randomised controlled trial. Patients due for TKR surgery will invited to take part in a pilot trial and randomised to surgery with or without a tourniquet with a view to recruiting 50 patients. All patients will undergo a Magnetic Resonance (MR) imaging scan of their brain before and 2 days after surgery to look for evidence of clots and debris in the brain as a result of the surgery. Patient tests of cognitive brain function will be collected before surgery and compared with the same tests up to 2 days after the surgery to look for evidence of disturbances in cognition. Other potentially important outcomes including evidence of symptomatic VTE, knee pain and function, health-related quality of life and the need for further revision procedures within 12 months will also be collected and tested. Integrated qualitative research study. An interview study of around 30 patients and around 20 surgeons will capture the views and opinions of both groups regarding the acceptability of the pilot trial and potential barriers and solutions to the feasibility of a full trial. Retrospective multi-centre cohort study. A study of an existing database of TKR surgery in England and Wales (National Joint Registry-NJR) will be undertaken. The NJR collected tourniquet use for TKR surgery from April to December 2003 and records all revision surgery. These data will be mapped to other existing databases of deaths and hospital reported VTE. The study will seek to estimate the relationship, if any, that tourniquet use has on the rates of post-operative death, VTE and revision surgery.This study will establish if patients are prepared to be randomised and surgeons are prepared to recruit their patients in a trial. It will also establish if using a tourniquet for TKR increases the risk of clots and debris in the brain and if there is a suitable method for determining whether these affect brain function. Other important outcome measures including VTE, death and revision surgery will also have been tested and evaluated in preparation for potential assessment in a full trial. At the end of the study a meeting with stakeholders (patients, surgeons, public representatives and researchers) will be held to agree the feasibility and choice of primary outcome measure for a full trial in light of the new study data.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL