Pre-operative Intravenous Steroid in Total Knee Replacement for Pain Relief and Recovery
Condition: Osteoarthritis, Knee
MeSH terms: Osteoarthritis, Knee
Study type: Interventional
Phase: Phase 4

Summary: 
      Osteoarthritis of the knee is a common and important condition in our society. Despite
      various anesthetic methods and pain medications, pain after operation still remains as a
      challenge.

      Steroids plays a role in decreasing the inflammatory reaction and stress response from
      surgery.

      This study is to evaluate the use of an additional steroid injection, on top of usual pain
      killers and anesthesia, on the effect of pain control and recovery after total knee
      replacement.

      50 subjects will be recruited, half of them will be randomized to receive a single dose of
      steroid injection before operation while the other half will receive a placebo. All the
      doctors, patients and physiotherapists are not aware of the allocation. Apart from the
      steroid or placebo injection, all the other treatment (eg: surgery, medications,
      rehabilitation protocol etc) will be the same. Doctors and physiotherapists will assess the
      subjects at 24, 30, 48 hours after surgery and upon discharge for their pain relief and
      recovery. Any complications will also be documented.
    

Detailed description: 
      Osteoarthritis of the knee is a common and important disease in the population. As a joint
      replacement centre, around 600 total knee replacements were performed in Queen Elizabeth
      Hospital and Buddhist Hospital per year. Despite multiple anesthetic methods and analgesics
      protocols, post-operative pain remains a significant problem.

      Perioperative use of steroids has been shown to reduce postoperative nausea and vomiting. In
      both orthopaedic and non-orthopaedic operations, a single high dose of pre-operative steroid
      was also found to be effective in reducing early postoperative pain.

      The hypothesis is that steroids help reduce post-operative inflammation and surgical stress
      response. Inflammatory markers such as IL-6 and C-reactive protein showed significant
      reduction after administration of perioperative steroids.

      In a Denmark randomized-controlled trial published in 2010, the authors found that a single
      high-dose of methylprednisolone significantly reduce post-operative pain upto 48 hours in
      patients undergoing unilateral primary total knee replacement. Another randomized-controlled
      trial conducted in Korea in 2013 also showed significant pain control with less opioid
      consumption 6-24 hours after total knee replacement using dexamethasone. A group of United
      States researchers demonstrated that 3 doses of perioperative low dose hydrocortisone could
      also reduce post-bilateral total knee replacement pain at 24 hours with significant greater
      range of motion in a randomized-controlled trial published in 2012. However, there is no data
      on the effect of perioperative steroid use in Chinese population receiving total knee
      arthroplasty.

      Upon induction, the intervention group will receive 125mg methylprednisolone diluted in 2.1ml
      of diluent intravenously. The placebo group will receive 2.1ml of 0.9% intravenous saline,
      which is transparent and has no difference in appearance to methylprednisolone.

      All subjects will undergo total knee replacement using same implant (Zimmer NexGen LPS Flex)
      by same surgeons. All operations will be done under spinal anesthesia injecting 1.8-2.5ml
      0.5% Bupivacaine into L3/4 or L4/5 disc space without fentanyl or other analgesics.
      Pre-operative, perioperative and postoperative analgesic regimen will be standardised.

      Subjects will be assessed at 24, 30, 48 hours after surgery and upon discharge by
      physiotherapists. During each assessment, pain from operated knee will be assessed with 100mm
      visual analogue scale with patients performing different tasks, i.e.: at rest, maximal knee
      flexion, straight knee raise with 45 degree hip flexion, frame walking for 5m. Range of
      movement will also be documented in each assessment. Time to achieve independent frame
      walking and length of stay will be recorded in terms of days.

      Analgesic consumption will be calculated with reference to the total amount of morphine
      administered through patient-controlled analgesia in the first 48 hours and the total dosage
      of rescue analgesia (DF118) required.

      To assess the severity of inflammation, knee circumference (measured at the most superior
      border of patella in cm) will be measured before operation and 48 hours after operation.
      Biochemically, blood will be taken for C-reactive protein (CRP) in day 1 after surgery and
      compared with pre-operative CRP. Renal function and blood sugar will also be closely
      monitored to detect any hypokalaemia or hyperglycaemia. Subjects will also be asked to rate
      the sleep quality using a 100mm visual analogue scale (0 = worst sleep, 100 = best sleep).
    

Intervention name(s): Methylprednisolone Sodium Succinate; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): single intravenous dose of 125mg methylprednisolone diluted in 2.1ml of diluent given on induction of total knee replacement; 0.9% intravenous saline (2.1ml) intravenously on induction of total knee replacement
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: single-centre, double-blind, placebo-controlled randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Knee; Pain; Recovery; Steroid; Replacement; Arthroplasty