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

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.

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