Pre-operative Intravenous Steroid in Total Knee Replacement for Pain Relief and Recovery

Osteoarthritis, Knee Clinical Trial

Official title:

Pre-operative Intravenous Steroid in Unilateral Primary Total Knee Replacement for Pain Relief and Recovery: A Double-Blind Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03082092
• Other study ID #: PISTKR
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2017
• Est. completion date: June 1, 2019

Study information

• Verified date: August 2019
• Source: Queen Elizabeth Hospital, Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 1, 2019
• Est. primary completion date: June 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Methylprednisolone Sodium Succinate
single intravenous dose of 125mg methylprednisolone diluted in 2.1ml of diluent given on induction of total knee replacement
• Placebos
0.9% intravenous saline (2.1ml) intravenously on induction of total knee replacement

Locations

Country	Name	City	State
Hong Kong	Queen Elizabeth Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Queen Elizabeth Hospital, Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain from operated knee using 100mm visual analogue scale	during walking 5 metres with frame, using 100mm visual analogue scale	24 hours after surgery
Secondary	Pain from operated knee (other than primary outcome) using 100mm visual analogue scale	during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, using 100mm visual analogue scale	24 hours after surgery
Secondary	Pain from operated knee using 100mm visual analogue scale	during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, walking 5 metres with frame, using 100mm visual analogue scale	30 hours after surgery
Secondary	Pain from operated knee using 100mm visual analogue scale	during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, walking 5 metres with frame, using 100mm visual analogue scale	48 hours after surgery
Secondary	Pain from operated knee using 100mm visual analogue scale	during rest, maximal knee flexion, straight knee raise with 45 degree hip flexion, walking 5 metres with frame, using 100mm visual analogue scale	upon discharge usually around post operative day 7
Secondary	Range of movement from operated knee	Maximal knee flexion and maximal knee extension	24, 30, 48 hours after surgery, upon discharge usually around post operative day 7
Secondary	Time to achieve independent frame walking	in terms of days	upon discharge usually around post operative day 7
Secondary	Length of stay	from day of admission to day of discharge, in terms of days	upon discharge usually around post operative day 7
Secondary	Patient-controlled analgesia consumption	Total morphine use in patient-controlled analgesia	48 hours after surgery
Secondary	Rescue analgesics consumption	amount of rescue analgesics (DF118) needed	upon discharge usually around post operative day 7
Secondary	Knee circumference of the operated knee	measured at most superior border of patella in cm	48 hours after surgery
Secondary	C-reactive Protein	blood taking for C-reactive protein	day 1 after surgery
Secondary	Sleep quality using 0-100 visual analogue scale	0-100 visual analogue scale, 0=worst sleep, 100= best sleep	day 1 after surgery