High-Dose Steroid for Knee Arthroplasty Patients Expected to Have Postoperative Pain

Study Overview
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Brief Summary
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The purpose of the Study is to test a higher dose of steroids(Dexamethasone) given just prior to surgery in the setting of Fast-Track Knee surgery with Arthroplasty in a group of expected High Pain Responders and the effect on postoperative pain and postoperative inflammation.

Detailed Description
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This study compares a new High-Dose dosage of steroids in the treatment of postoperative pain after Knee Arthroplasty in a Fast-Track setting in a group of expected High Pain Responders. The investigators compare the already used dose(medium dose) with a new high dose(HD) steroid given as an intravenous bolus after the spinal anaesthesia has been given, but before the surgery starts. The hypothesis is that by attenuating the inflammatory response to the surgery itself by the steroid Dexamethasone, the investigators expect a reduction in postoperative pain upon ambulation 24 hours after unilateral Knee Arthroplasty. Patients referred to Unilateral Total KneeArthroplasty because of knee-osteoarthritis at Hvidovre Hospital, Capital Region of Denmark or Vejle Hospital, South Region of Denmark are screened and offered inclusion in the study. The two groups will be randomized and double blinded. One group will be treated, as the current guideline in the investigator's Orthopedic fast-track Arthroplasty center, with the medium dose of steroid (0,3 mg dexamethasone/kg bodyweight). The other group wil be treated with a high dose of steroid (1,0 mg dexamethasone/kg bodyweight). The patients will be monitored the first 7 days after surgery, during the admission to the hospital, and by a Pain-diary in the patients own home. Blood tests will be taken preoperatively and postoperatively to determine the effect of the highdose steroid on the inflammatory response.

Official Title
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High-Dose Steroids in High Pain Responders Undergoing Total Knee-arthroplasty: A Randomized Double Blinded Controlled Trial

Conditions
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Postoperative Pain, Postoperative Nausea and Vomiting, Knee Osteoarthritis, Perioperative/Postoperative Complications, Surgery, Opioid Use, Catastrophizing Pain, Chronic Pain

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 40 and 90. Booked for unilateral knee-arthroplasty. Is able to take part in the investigation(selfreported pain and nausea/vomiting) Understands Danish or English, or has a translator available. Signed written consent. A daily use of 30 mg or more of morphine or morphine equivalents . A pain catastrophizing scale(PCS) score of >20. Exclusion Criteria: Insulin-dependent diabetes melitus. Ongoing treatment with systemic glucocorticoids or immunosuppressing treatment(apart from inhaled glucocorticoids). Pregnancy/Breastfeeding Allergies for the investigational drug. A history of schizophrenia or bipolar diseases, or patients with permanent use of antipsychotic medication.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized double blinded controlled trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose Dexamethasone<br>An intravenous bolus dose of Dexamethasone 1 mg/kg bodyweight administered preoperatively before surgery. | Drug: Dexamethasone<br>* An intravenous bolus dose of dexamethasone given prior to surgery.<br>* Other names: Dexa-ratiopharm;|
| Active Comparator: Medium dose Dexamethasone<br>An intravenous bolus dose of Dexamethasone 0,3 mg/kg bodyweight administered preoperatively before surgery. | Drug: Dexamethasone<br>* An intravenous bolus dose of dexamethasone given prior to surgery.<br>* Other names: Dexa-ratiopharm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain after 24 hours: VAS | The amount of patients with moderate postoperative pain in a 5 meter walk test 24 hours postoperatively after total knee-arthroplasty. Pain is monitored by the Visual Analog Scale(VAS) 0-100 mm, where 0 is no pain and 100 mm is the worst pain. Moderate pain is considered a VAS >30 mm. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative opioid usage | The amount of rescue opioids given in the postoperative period, and until 7 days after surgery. | 7 days | 
| Postoperative antiemetics usage | The amount of rescue antiemetics given in the postoperative period, and until 7 days after surgery. | 7 days | 
| The inflammatory response expressed by C-reactive protein(CRP). | The inflammatory response is monitored by the blood-sample c-reactive protein(CRP) and analyzed to se the possible attenuation of the response because of dexamethasone. | 2 days | 
| Postoperative pain summarized in the first 7 days | Pain summarized over the first 7 days after surgery, assessed by a summation of the Visual Analog Scale(VAS)-scores in the first 7 days as noted in the pain diary filed in by the participants. Pain is monitored by the Visual Analog Scale(VAS) 0-100 mm, where 0 is no pain and 100 mm is the worst pain one can imagine. Moderate pain is considered a VAS >30 mm. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee Arthroplasty, Knee Replacement, Perioperative Medicine