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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Postoperative Pain; Knee Osteoarthritis; Surgery; Postoperative Nausea and Vomiting; Opioid Use; Perioperative/Postoperative Complications; Catastrophizing Pain
• Intervention / Treatment: Drug: Dexamethasone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital, Capital Region of Denmark.
  • Vejle, Denmark, 7100
    • Vejle Sygehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Why still in hospital, an audit into the reasons the patient has not yet been discharged from the ward.	An investigation into reason of why our patients remain in the hospital in the days after total Knee Arthroplasty in our Fast-Track center. This is investigated through a questionnaire previously used in a similar investigation in our center. The questionnaire is filled in by our project nurse. the questionnaire is a checkmark schedule with predetermined reasons to stay in hospital like low bloodpressure, sedation, dizzyness, lack of physiotherapy and medical and surgical complications. The outcome assesment will be descriptive.	7 days.

Collaborators and Investigators

• Sponsor: Copenhagen University Hospital, Hvidovre
• Collaborators: Sygehus Lillebaelt
• Investigators: Study Director: Nicolai Bang Foss, Dr.med., Dept. of Anaesthesia, Hvidovre Hospital, Capital Region of Denmark.

Publications and helpful links

General Publications

• Nielsen NI, Kehlet H, Gromov K, Troelsen A, Husted H, Varnum C, Kjaersgaard-Andersen P, Rasmussen LE, Pleckaitiene L, Foss NB. High-dose steroids in high pain responders undergoing total knee arthroplasty: a randomised double-blind trial. Br J Anaesth. 2022 Jan;128(1):150-158. doi: 10.1016/j.bja.2021.10.001. Epub 2021 Nov 5.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2019
• Primary Completion (Actual): January 1, 2021
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Knee Arthroplasty; Knee Replacement; Perioperative Medicine
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Nausea; Pain, Postoperative; Vomiting; Osteoarthritis, Knee; Chronic Pain; Postoperative Complications; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: NBF_HK_02_2018

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No