Surgical Techniques in Arthroplasty of the Knee (STArK) 1 Trial
Surgical Techniques in Arthroplasty of the Knee (STArK) 1 Trial
Study Background Osteoarthritis of the knee is a common degenerative musculoskeletal
 condition which affects nearly five million people in the United Kingdom. Some patients will
 require total knee replacement surgery if their symptoms of pain and disability are not
 controlled adequately by so-called 'conservative' measures such as weight-loss, activity
 modification and analgesic (pain-killer) medication.

 Over the past ten years our understanding of pain-relief strategies during total knee
 replacement, often termed 'Enhanced Recovery' principles, has helped improve patient care and
 reduced length of hospital admission. 'Enhanced Recovery' principles recommend the use of
 analgesic medications which can be delivered in a variety of ways e.g. tablets and
 injections. This is termed 'multi-modal' analgesia.

 Prior to total knee replacement, the patient will receive an injection around the nerves in
 the spine (regional anaesthesia) which numbs the patient from the waist down and allows the
 surgeon to perform the operation in a safe and pain-free manner. During the operation,
 surgeons often choose to deliver extra local anaesthetic to prolong the degree of pain-relief
 in the immediate post-operative period. This can enable patients to mobilise early and is
 associated with greater long-term satisfaction.

 There are two main methods of delivering this extra form of pain-relief during the operation.
 Peri-articular injection involves multiple injections of local anaesthetic into the
 soft-tissues surround the knee. In contrast, Intra-articular injection involves a single
 injection directly into the knee joint once the operation is finished. Currently, there is no
 clear evidence available to Orthopaedic surgeons to inform us which technique is better at
 providing pain relief for patients undergoing total knee replacement surgery.

 All patients undergoing total knee replacement surgery for osteoarthritis of the knee will be
 invited to participate in this study. We intend to recruit a total of 120 patients. During
 the patient's total knee replacement surgery, they shall receive an injection of local
 anaesthetic around the soft-tissues of the knee (Peri-Articular Injection) or directly into
 the knee joint itself (Intra-Articular Injection). The decision regarding which treatment
 they receive is decided entirely by randomisation.

 Following the operation, a member of the research team will assess the patient on the ward to
 collect information regarding levels of pain and overall satisfaction. The type of injection
 received shall be kept secret from both the patient and the member of the research team
 collecting the post-operative pain scores.

 After the patient has been safely discharged from hospital, we intend to follow-up all
 participants for one year. This will involve routine clinic appointments at six weeks and
 twelve months following surgery. This will involve review and clinical examination by a
 member of the orthopaedic team who have treated the patient whilst in hospital and/or a
 member of the research team.

 In addition, all patients will be asked to complete a questionnaire at twelve months
 regarding their level of function and pain. These questionnaires have been used widely in the
 medical literature and have a strong evidence base for their use.

 What is the aim of this study? The aim of this study is compare the amount of pain relief
 provided by two different methods of local anaesthetic injection techniques used in total
 knee replacement surgery. In addition, we would like to know if this influences the patient's
 immediate and long-term recovery after surgery.
The aim of this study is compare the amount of post-operative pain relief provided by two
 different methods of local anaesthetic injection techniques used in total knee replacement
 surgery.

 'Enhanced Recovery After Surgery' protocols has significantly shortened recovery-time and
 length of hospital admission after total knee replacement (TKR). A major factor in this
 improvement has been the incorporation of multi- modal therapies which deliver adequate pain
 relief, limit post-operative nausea and enable early mobilisation.

 Peripheral nerve blocks are performed by the anaesthetist immediately prior to surgery. This
 involves injecting local anaesthetic around the nerves which supply sensation around the
 knee. Injecting directly into the nerve can damage it and lead to significant disability. For
 this reason peripheral nerve blocks are often performed under ultrasound guidance. This can
 be time-consuming and does not negate the risk of nerve injury.

 Peri-articular infiltration is performed during the operation by the surgeon. In the knee
 this involves injecting a solution of local anaesthetic into multiple specified soft-tissue
 and bony regions around the knee. It is performed blind without ultrasound guidance and also
 carries risk of nerve injury.

 Intra-articular injections involve the surgeon injecting local anaesthetic solution into the
 knee joint itself. During TKR, this can be performed after closure of the joint capsule
 immediately prior to skin closure. This avoids risks to nerves and arteries as it is placed
 into the large knee joint, and not blindly around the joint capsule. In addition, it is
 simple to perform and less time-consuming than peri-articular infiltration.

 Randomised controlled trials have previously compared femoral (peripheral) nerve blocks to
 periarticular infiltration, periarticular infiltration with and without posterior capsule
 infiltration, and periarticular infiltration to the front versus the back of the knee.
 However, to our knowledge the technique of intra-articular injection has not been compared to
 peri- articular infiltration for immediate post-operative analgesia following total knee
 arthroplasty

 Study Design A double-blind randomised controlled trial (RCT) will be conducted in a single
 hospital, with four Consultant Knee Surgeons recruiting patients. It is anticipated from a
 previous RCT performed at the same centre, that recruitment be completed within 2 years.

 Participants All patients undergoing primary total knee replacement for osteoarthritis under
 the care of 4 Consultant Orthopaedic Surgeons at the Royal Infirmary of Edinburgh will be
 assessed for eligibility for study enrolment.

 All patients will receive trial information (patient information sheet) when they are placed
 on the waiting list for TKR. Patients currently wait 12 weeks for surgery. When patients are
 reviewed at a pre-assessment clinic 2-4 weeks prior surgery, those who fulfil the inclusion
 criteria will have the trial explained in full by the research team, supervised by the lead
 investigator Ms Chloe Scott, and will decide whether they wish to be involved. Informed
 consent will be obtained at this stage. Patients will then have 2-4 weeks before surgery to
 opt out of the study if they wish.

 Power Calculation Audit of 10 TKR patients measuring VAS pain scores at 6 and 24 hours has
 demonstrated a standard deviation of 2.14 points. The minimum clinically important difference
 (MCID) for this score is 12mm (1.2 points). Assuming approximate normality for the VAS,
 primary outcome data on 102 patients (51 in each arm) will be required for 80% power at 5%
 significance. Allowing for a dropout rate of 10%, 120 patients will be recruited.

 Randomization A total of 120 participants will be randomized in a 1:1 ratio to either
 Treatment Group 1 (periarticular infiltration) or Treatment Group 2 (intraarticular
 injection) using the sealed opaque envelope randomization technique. This will be performed
 after spinal anaesthetic has been administered before surgery commences.

 Baseline information All patients will be initially evaluated with a complete history and
 physical examination. For all patients entering the study the following baseline information
 will be recorded: Age, sex, BMI, Kellgren-Lawrence grade of osteoarthritis, preoperative
 analgesia regime, length of knee pain duration, employment status, and postcode. Baseline VAS
 Pain scores, Oxford Knee Scores and EQ-5D scores will be collected as is routine for all of
 our arthroplasty patients.

 Peri-operative Protocol All patients will be admitted on the day of surgery and undergo a
 standardised enhanced recovery anaesthetic protocol including spinal anaesthetic (with no
 intrathecal diamorphine) and no peripheral nerve blocks (femoral, sciatic or adductor canal).

 All patients will undergo a cemented Triathlon (Stryker, Mahwah, NJ, USA) cruciate retaining
 TKR.

 All patients will be prescribed standardised post-operative analgesia including Oxycodone MR
 15mg twice daily for 4 doses with stepdown to weaker opiate, usually Cocodamol 30/500 2 tabs
 4 times per day, Oxycodone IR 5-10mg prn for breakthrough pain.

 Patients will be placed first or second on the operating list to enable VAS pain scores to be
 collected at the assigned times.

 Multimodal injection The injection will consist of the same drugs for all patients: 150mg
 levobupivacaine 0.25%, 10mg morphine; and 30mg ketorolac made up to a volume of 150ml with
 saline.

 The difference between treatment groups is how the multimodal injection is administered:
 either by periarticular infiltration around the knee, or by simple intra-articular injection
 after the knee joint capsule has been closed.

 Treatment group 1: Periarticular infiltration

 Intra-operatively after bone cuts have been made and prior to implant cementation, the
 multimodal injection will be infiltrated around the knee at 6 specific sites:

 1. Medial femoral condyle periosteum

 2. Medial gutter

 3. Lateral femoral condyle periosteum

 4. Lateral gutter

 5. Posteromedial capsule

 6. Posterolateral capsule

 Treatment Group 2: Intra-articular infiltration After implant cementation and watertight
 joint capsular closure, the multimodal injection will be injected intra-articularly through
 the closed capsule.

 Post-operative protocol and Follow-up Postoperatively patients will complete a VAS pain score
 at 6, 12 24 and 48 hours postoperatively with research staff blinded to the infiltration
 technique employed. All analgesia required in the first 24 hours will be recorded and an
 opiate equivalency dose calculator used to determine opiate intake (Joint Formulary Committee
 2016). At 48 hours, in addition to recording a VAS pain score, patients will be asked how
 satisfied they were with their pain relief as scored on a 5 point Likert score from very
 satisfied to very dissatisfied.

 Patients will then undergo routine postoperative management with review by arthroplasty
 practitioners blinded to their treatment arm at 6 weeks where they will be examined and will
 be asked to complete an adverse events questionnaire.

 Patient reported outcomes including Oxford Knee Scores and EQ-5D scores will be collected as
 standard at 12 months.
Inclusion Criteria:

 -  Primary knee osteoarthritis requiring Total Knee Replacement surgery

 -  Planned for cruciate retaining prosthesis without patella resurfacing

 -  Patient is able to give informed consent

 -  Patient resides locally and will be available for follow up

 Exclusion Criteria:

 -  Inflammatory arthropathy

 -  Preoperative morphine based analgesia

 -  Renal insufficiency (GFR<30)

 -  Allergy to study drugs

 -  Spinal anaesthetic not possible

 -  Neurological disorder affecting the lower limbs