Short summary

Aim of the study is to compare the effect of a repeat moderate dose of glucocorticoids postoperatively after preoperative high dose upon postoperative pain after TKA in an HPR population to a standard single high dose systemic preoperative administration in an HPR population.

As a standard procedure, all patients referred to the outpatient clinic due to suspected degenerative knee disease will be asked to fulfill the PCS. If TKA is decided, patients with a PCS score above 20 will be treated with intravenously administered Dexamethasone 1 mg/kg as a rounded-up-dose to closest 10 mg according to our guideline for FAST-TRACK TKA.

The repeat-dosing group (RDG) will receive a dose of 24 mg dexamethasone tablets at 9-11 pm on the first postoperative day. The control-group (CG) will receive placebo tablets at 9-11 pm on the first postoperative day.

Rationale

BACKGROUND

Total hip and knee arthroplasty (THA/TKA) are frequently performed procedures and are expected to increase in numbers along with the growing elderly population the next decade. TKA is suitable for FAST-TRACK surgery, and is often performed as outpatient surgery with no hospital overnight stay.

Challenges in FAST-TRACK surgery include postoperative pain, nausea and vomiting (PONV), complications due to rescue-analgesics and surgical complications. Pain is a well-known clinical problem, with up to 75% of TKA patients experiencing moderate to severe pain the first day after surgery, and 30-40% still experiencing moderate to severe pain 2 weeks after surgery, potentially delaying ambulation and recovery within the first weeks. The role of severe acute postoperative pain upon the development of chronic pain is debatable, but important.

Data from our recently finished study in High Pain Responders (HPR), defined as patients with a score above 20 on the Pain Catastrophizing Scale (PCS), receiving preoperative high dose dexamethasone (Nielsen et al.: IN PREPARATION, clinicaltrials.gov ID NCT03763734, EudraCT 2018-002635-23, VEK H-18034778) found a persistent moderate to severe pain in 40 % of patients, at time 48 hours after surgery, corresponding to the time when the physiological effect of our dexamethasone intervention declines. Moderate to severe pain (VAS >30) 24 hours postoperatively during a 5-meter walk test was associated with relapse pain at 48 hours.

Other studies have made attempts of investigating the effect of a repeated dose of steroids after TKA and THA, but all have done so with a postoperative injection of low dose steroids14-20. No previous studies have, to our knowledge, investigated the effects of repeat dosing after a preoperative high dose of steroid, and none focused on patients selected by their postoperative pain response. In spite of many studies and systematic reviews on the subject, the optimal timing and dose for steroid-intervention in TKA in different patient groups is still inadequately understood.

Description of the cohort

- Primary unilateral TKA patients

- Age older then 40 years

- High Pain Responders (HPR), defined as patients with a score above 20 on the Pain Catastrophizing Scale

Data and biological material

Primary outcome

Moderate to severe pain (VAS > 30) upon ambulation in a 5-meter walk test, on the morning of day 2 after TKA surgery.

Secondary outcomes

• Cumulated pain upon ambulation in a 5-meter walk test day 2-3.

• Cumulated pain score at rest, upon ambulation in a 5-meter walk test and at night from day 2-7.

• Quality of sleep, lethargy, dizziness and nausea pre- and postoperatively from day 0 to day 7.

• Cumulative use of rescue-analgesics per day in hospital day 0 to discharge, and at home from day of discharge to day 7.

• Patient satisfaction with analgesic-regimen at day 7.

• Length of stay (LOS) in hospital, and reasons for prolonged stay (>2 postoperative days) registered at "Why still in hospital".

• Reasons for re-admissions within 30 days.

• Morbidity and mortality (30-day follow-up by Electronic Patient Journal (EPJ) or telephone).

Collaborating researchers and departments

Department for Orthopedic Surgery , Vejle Hospital. Department for Anesthesia. Hvidovre Hospital