Clinical trial NCT03082092: Pre-operative Intravenous Steroid in Total Knee Replacement for Pain Relief and Recovery
Official title: Pre-operative Intravenous Steroid in Unilateral Primary Total Knee Replacement for Pain Relief and Recovery: A Double-Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis, Knee
Keywords: Knee
Pain
Recovery
Steroid
Replacement
Arthroplasty
Lead sponsor: Queen Elizabeth Hospital, Hong Kong
Sponsor class: OTHER
First posted: 2017-03-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: single-centre, double-blind, placebo-controlled randomized controlled trial
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: Inclusion Criteria:

* Elective unilateral total knee replacement for primary osteoarthritis of knee
* ASA (American Society of Anesthesiologists) grading 1 or 2

Exclusion Criteria:

* Rheumatoid arthritis or seronegative arthritis
* Allergy to any medications used in the standard protocol (Methylprednisolone, adrenaline, ropivacaine, ketorolac, bupivacaine, ketorolac, pepcidine, transamin, gabapentin, voltaren, panadol, DF118)
* Chronic opioid use
* Substance dependence
* Patients attending chronic pain clinic
* Psychiatric or neurological condition that may influence pain perception or reporting
* Chronic illness that preclude the use of the medications in the standard protocol
* Hepatitis B carrier or Elevated bilirubin or ALT
* Active peptic ulcer disease
* Uncontrolled diabetic patients with HbA1c \>7% in recent 3 months

Primary outcomes:
measure: Pain from operated knee using 100mm visual analogue scale
timeFrame: 24 hours after surgery
Secondary outcomes:
measure: Pain from operated knee (other than primary outcome) using 100mm visual analogue scale
timeFrame: 24 hours after surgery
measure: Pain from operated knee using 100mm visual analogue scale
timeFrame: 30 hours after surgery
measure: Pain from operated knee using 100mm visual analogue scale
timeFrame: 48 hours after surgery
measure: Pain from operated knee using 100mm visual analogue scale
timeFrame: upon discharge usually around post operative day 7
measure: Range of movement from operated knee
timeFrame: 24, 30, 48 hours after surgery, upon discharge usually around post operative day 7
measure: Time to achieve independent frame walking
timeFrame: upon discharge usually around post operative day 7
measure: Length of stay
timeFrame: upon discharge usually around post operative day 7
measure: Patient-controlled analgesia consumption
timeFrame: 48 hours after surgery
measure: Rescue analgesics consumption
timeFrame: upon discharge usually around post operative day 7
measure: Knee circumference of the operated knee
timeFrame: 48 hours after surgery
measure: C-reactive Protein
timeFrame: day 1 after surgery
measure: Sleep quality using 0-100 visual analogue scale
timeFrame: day 1 after surgery
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
Study officials:
References:
citation: Cheng BLY, So EHK, Hui GKM, Yung BPK, Tsui ASK, Wang OKF, Poon MWY, Chan ACM, Wong SHS, Li W, Yip PSC. Pre-operative intravenous steroid improves pain and joint mobility after total knee arthroplasty in Chinese population: a double-blind randomized controlled trial. Eur J Orthop Surg Traumatol. 2019 Oct;29(7):1473-1479. doi: 10.1007/s00590-019-02469-5. Epub 2019 Jun 20.