Effects of Combined Topical and Systemic Steroid Administrations on Better Early Postoperative Pain Management in Total Knee Arthroplasty

April 2, 2019 updated by: Dr. Chan Ping-Keung, The University of Hong Kong

Effects of Combined Topical and Systemic Steroid Administrations on Better Early Postoperative Pain Management in Total Knee Arthroplasty: a Prospective Double-blinded Placebo Controlled Randomised Clinical Trial

With the aging of population, osteoarthritis of knees and hips has become major orthopaedic problems in Hong Kong. Osteoarthritis of knees and hips is associated with significant pain problems and functional disability. Total joint replacement is the ultimate surgical procedure to deal with such problems.

However total joint replacement is associated with significant tissue damage and post-operative pain problems, which would affect post-operative recovery and rehabilitation.

The primary aims of total knee replacement are improvement in functional activities and reducing pain due to degenerated knee joints. However, there are around 20-30% of patients would develop significant pain problems despite uncomplicated total knee replacement. It accounts for major post-operative problems and burdens.

Procedure specific analgesic method with multi-model analgesia technique is well-known to be useful in post-operative pain management, which reduces the post-operative pain score. Despite the use of multi-modal analgesic technique, pain after total joint replacement is still an unsolved issue. It prolongs the recovery period and increases post-operative analgesic consumption.

Dexamethasone is a glucocorticoid which is associated with anti-inflammatory response. It is well known to have prophylaxis effect on post-operative nausea and vomiting. Perioperative single dose of systemic dexamethasone have shown to be useful for reduction in pain and cumulative opioid consumption. Meta-analysis from De Oliveira et al supports that dexamethasone (up to 0.2 mg/kg) is a safe and effective multimodal pain strategy after surgical procedures. However, this dose recommendation is not surgery specific. Recently, one review also supports even higher systemic steroid dose to ameliorate post-operative pain after hip and knee surgery. This is based on 3 RCTs using high dose steroid (125 mg methylpresnisolone and 40mg dexamethasone). However, large-scale safety and dose-finding studies are warranted before final recommendations. In view of these, it is essential to have more RCTs evaluating the optimal dose of steroid for pain management after hip and knee surgery.

Chronic steroid use is known to be associated with infection and gastrointestinal bleeding. It is essential to evaluate the safety profile associated with the use of high dose steroid -- risk of infection, gastrointestinal bleeding and hyperglycaemia etc. Published reviews have not raised concerns with perioperative single-dose administration in surgical patients. For hyperglycemia, P. Hans et al have shown that after the use of 10 mg dexamethasone, blood glucose level was increased in non-diabetic and type 2 diabetic patients undergoing abdominal surgery, in which glucose level and percentage change of glucose level were significant higher in diabetic group with glucose level peaked at around 2 hours after injection. Recent study by Basem B. Abdelmalak et al have shown that there was a comparable dexamethasone-induced hyperglycemic response in the diabetic and non-diabetic groups. Nevertheless, there was dexamethasone-induced hyperglycaemia in both groups. Close monitoring of blood glucose and correction of hyperglycaemia in those patients are recommended.

In previous studies, high-dose dexamethasone has shown to be effective and safe to be administered. The addition of dexamethasone to the multi-model analgesia is associated with anti-inflammatory response, thus extending the analgesic effect period for up to 72 hrs as purposed to 24-48 hrs. However, the recommended dose of dexamethasone is not surgery-specific and needs more studies to define the optimal dose. Therefore, it is essential to have more RCTs which evaluate the optimal dose of steroid for better pain management after hip and knee surgeries.

Investigators have recently performed a study evaluating the effect of high-dose dexemathasone. It is shown that dexamethasone 16mg is effective in managing acute postoperative pain after total knee arthroplasty. Another study have been performed by investigators to show the effectiveness of local application of triamcinolone to surgical sites after total knee arthroplasty.

In view of the above findings, the aim of this study is to compare the effect of intravenous dexamethasone, local application of triamcinolone and combined use of intravenous dexamethasone and local application of triamcinolone after total knee arthroplasty.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Department of Orthopaedics and Traumatology, The University of Hong Kong
        • Contact:
          • Ping Keung Chan, MBBS
          • Phone Number: +852 2255 4654
          • Email: ortho@hku.hk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ASA I-III
  • Age 18-80 years old (For patients recruited from the Duchess of Kent Children's Hospital at Sandy Bay, they will also be aged from 18 to 80 years old)
  • Scheduled for elective primary unilateral total knee replacement
  • Chinese patients
  • Able to speak and understand Cantonese
  • Able to provide informed oral and written consent

Exclusion Criteria:

  • Revision total knee replacement
  • Single stage bilateral total knee replacement
  • Known allergy to opioids, local anaesthetic drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDS) including COX-2 inhibitors
  • History of chronic pain other than chronic knee pain
  • History of insulin dependent diabetic mellitus, but not diabetic mellitus on oral hyperglycaemic agents
  • History of hepatitis B or C carrier
  • History of peptic ulcer
  • Hx of tuberculosis
  • History of immunosuppression
  • Daily use of glucocorticoids
  • Daily use of strong opioids (morphine, fentanyl, hydromorphone, ketobemidone, methadone, nicomorphine, oxycodone, or meperidine)
  • History of severe heart disease (NYHA 2)
  • Alcohol or drug abuse
  • Impaired renal function, defined as preoperative serum creatinine level over 120 micromol/L
  • Pre-existing neurological or muscular disorders
  • Psychiatric illness or neurologic or psychiatric diseases potentially influencing pain perception
  • Impaired or retarded mental state
  • Difficulties in using patient controlled analgesia (PCA)
  • Pregnancy
  • Local infection
  • On immunosuppresants
  • Patient refusal

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Group dexamethasone
A syringe having 4ml of 4mg/ml of dexamethasone is used for intravenous injection
Drug: Dexamethasone
a syringe having 4ml of 4mg/ml of dexamethasone is used for intravenous injection.
EXPERIMENTAL: Group triamcinolone
1ml of 40mg triamcinolone is mixed in the syringes containing solution for intrarticualar local infiltration. The solution is injected intraarticularly.
Drug: Triamcinolone
1ml of 40mg triamcinolone is mixed in the syringes containing solution for intrarticualar local infiltration. The solution is injected intraarticularly.
EXPERIMENTAL: Group dexamethasone with triamcinolone
A syringe having 4ml of 4mg/ml of dexamethasone is used for intravenous injection. 1ml of 40mg triamcinolone is mixed in the syringes containing solution for intrarticualar local infiltration. The solution is injected intraarticularly.
Drug: Dexamethasone
a syringe having 4ml of 4mg/ml of dexamethasone is used for intravenous injection.
Drug: Triamcinolone
1ml of 40mg triamcinolone is mixed in the syringes containing solution for intrarticualar local infiltration. The solution is injected intraarticularly.
PLACEBO_COMPARATOR: Placebo group
A syringe having 4ml of saline is used for intravenous injection. 1ml of saline is mixed in the syringes containing solution for intrarticualar local infiltration. The solution is injected intraarticularly.
Drug: Placebos
A syringe having 4ml of saline is used for intravenous injection. 1ml of saline is mixed in the syringes containing solution for intrarticualar local infiltration. The solution is injected intraarticularly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain (rest, moment)
Time Frame: From day 0 to 12 months after surgery
Numeric rating scale is used to assess pain intensity in persons who are able to self report. It ranges from 0 to 10. Pain increases with the number.
From day 0 to 12 months after surgery
PCA morphine consumption
Time Frame: From day 0 to the day on which patient was discharged from the hospital, assessed up to day 7
Number of demands and goods
From day 0 to the day on which patient was discharged from the hospital, assessed up to day 7
Active and passive ROM of knee (flexion and extension)
Time Frame: From day 0 to 12 months after surgery
Active and passive range of motion of knee (flexion and extension)
From day 0 to 12 months after surgery
Local Knee function e.g. KSKS
Time Frame: From day 0 to 12 months after surgery
Knee society knee score is a total score which rates the knee joint and its function. Higher score represents better knee recovery. It ranges from 0 to 100. Total score is the sum of subscores. Subscales are pain, passive range of motion, stabilty, fixed flexion contracture, extension lag and alignment. Pain ranges from 0 to 50. Higher score represents milder pain. Passive range of motion ranges from 0 to 25. Higher score represents better recovery. Stability ranges from 0 to 25. Higher score represents better recovery. Fixed flexion contracture ranges from 0 to -15. Lower score represents worse recovery. Extension lag ranges from 0 to -15. Lower score represents worse recovery. Alignment ranges from 0 to -20. Lower score represents worse recovery.
From day 0 to 12 months after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 26, 2018

Primary Completion (ANTICIPATED)

January 1, 2020

Study Completion (ANTICIPATED)

January 1, 2021

Study Registration Dates

First Submitted

March 29, 2019

First Submitted That Met QC Criteria

April 2, 2019

First Posted (ACTUAL)

April 3, 2019

Study Record Updates

Last Update Posted (ACTUAL)

April 3, 2019

Last Update Submitted That Met QC Criteria

April 2, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 18-234

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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