Peri-Articular-Multimodal Drug and Oral Celecoxib in Management of Postoperative Pain of Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study is a randomized-clinical-trial on 146 patients candidate for total knee arthroplasty (TKA) who were randomly allocated to three treatment groups, including 1) a cocktail consisting of bupivacaine, morphine, epinephrine, and ketorolac (n=48), 2) only epinephrine (placebo group) (n=49), and 3) 400mg celecoxib orally (control group) (n=49) using Random Allocation software. The injections and oral therapy were performed within 15 minutes before the surgical procedure. The study's primary outcome was the Knee Society Score (KSS) calculated at baseline, within six weeks and six months postoperatively. Range of motion (ROM) and Visual Analogue Scale (VAS) to assess pain intensity as the other primary outcomes were evaluated before the procedure, within 24 hours, 48 hours, and six weeks postoperatively.

Detailed Description
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This randomized clinical trial conducted on 146 patients undergone TKA in orthopedic hospitals affiliated at Isfahan University of Medical Science (IUMS) in 2021. The presence of osteoarthritis, making the patients candidate for primary unilateral total knee arthroplasty (TKA), and body mass index of 20-30 kg/m2 were determined as inclusion criteria. The Regional Bioethics Committee of IUMS approved the study protocol. This study was designed as a census study; therefore, all the patients who met the criteria for participation in this study were recruited. Participants were randomly divided into three groups using Random Allocation software, so each patient was provided with a specific number from 1-to-146 by the software and allocated to one of the groups. The investigator who performed the baseline and follow-up assessments and the patients were unaware of the study group; as the investigator was absent at the time of the surgery and all the patients administered a pill prior to the surgical procedure (one group was treated with celecoxib and the other two ones administered placebo similar in shape and color with celecoxib). The primary outcome was the Knee Society Score (KSS) calculated at baseline, within six weeks and six months postoperatively. Range of motion (ROM) and Visual Analogue Scale (VAS) to assess pain intensity as the other primary outcomes were evaluated before the procedure, within 24 hours, 48 hours, and six weeks postoperatively.

Official Title
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Comparing Pre-emptive Injection of Peri-Articular-Multimodal Drug With Oral Celecoxib for Postoperative Pain Management in Total Knee Arthroplasty: A Randomized Clinical Trial

Conditions
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Postoperative Pain, Total Knee Arthroplasty

Intervention / Treatment
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* Drug: Multimodal Drug
* Drug: epinephrine
* Drug: celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of osteoarthritis Candidate for primary unilateral TKA Body mass index of 20-30 kg/m2 Exclusion Criteria: Unable to follow-up the assessments Having more than 20% defects in medical records

Ages Eligible for Study
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Minimum Age: 37 Years
Maximum Age: 81 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal injection<br>The first group was treated using a preemptive periarticular injection of multimodal drugs. Therefore, a combination of drugs consisted of 50 mg bupivacaine hydrochloride 0.5% (AstraZeneca, Cenexi, France), 1 ml morphine sulfate 10 mg/ml (DarouPakhsh, Tehran, Iran), 300 mcg epinephrine (1:1000) (DarouPakhsh, Tehran, Iran) and 30 mg ketorolac (Caspian Tamin, Rasht, Iran) diluted by 0.9% sodium chloride solution to make a total 100 ml of injection drug was injected in periarticular area. The injections were done within 15 minutes before the incision in seven areas of the joint as followed: 15 ml in posterolateral soft tissue and lateral femoral periosteum, 15 ml posteromedial soft tissue and medial femoral periosteum, 20 ml inferomedial capsule, 20 ml superomedial capsule, 10 ml lateral capsule, 10 ml medial subcutaneous tissues and 10 ml lateral subcutaneous tissue. | Drug: Multimodal Drug<br>* The Multimodal Drug group received morphine, epinephrine, and ketorolac (n=48), The epinephrine group (placebo group) (n=49) received 300 mcg epinephrine (1:1000) (DarouPakhsh, Tehran, Iran) peri-articulary,and the celecoxib group(control group)(n=49) recieved 400mg celecoxib orally<br>* Other names: Case;|
| Experimental: epinephrine group (placebo group)<br>The second group received 300 mcg epinephrine (1:1000) (DarouPakhsh, Tehran, Iran) peri-articulary, similar to the first group. | Drug: epinephrine<br>* The second group received 300 mcg epinephrine (1:1000) (DarouPakhsh, Tehran, Iran) peri-articulary<br>* Other names: Placebo;|
| Experimental: celecoxib group (control group)<br>The third group administered celecoxib (200 mg) orally immediately before the surgery initiation. | Drug: celecoxib<br>* The third group administered celecoxib (200 mg) orally immediately before the surgery<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Measurements of Knee Society Score (KSS) | The Knee Society score is an assessment of the knee that comprises two arms, the functional ability and clinical examination scores, each with a 100-point denominator. One-hundred points are allocated to the functional capacity, including walking distance, stair-climbing ability, and the use of walking aids. | At the beginning of the study | 
| Baseline range of motion (ROM) | Knee ROM was evaluated using a standard goniometer | At the beginning of the study | 
| visual analogue scale (VAS) | Visual Analogue Scale (VAS) was used to evaluate the patient's postoperative pain intensity with a 0 to 10 rating scoring scale | 24 hours after the surgical procedure | 
| Range of motion (ROM) | Knee ROM was evaluated using a standard goniometer | 6 months after surgery | 
| Knee Society Score (KSS) | The Knee Society score is an assessment of the knee that comprises two arms, the functional ability and clinical examination scores, each with a 100-point denominator. One-hundred points are allocated to the functional capacity, including walking distance, stair-climbing ability, and the use of walking aids. | 6 months after surgery | 
| visual analogue scale (VAS) | Visual Analogue Scale (VAS) was used to evaluate the patient's postoperative pain intensity with a 0 to 10 rating scoring scale | 48 hours after the surgical procedure | 
| visual analogue scale (VAS) | Visual Analogue Scale (VAS) was used to evaluate the patient's postoperative pain intensity with a 0 to 10 rating scoring scale | Six weeks after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total knee arthroplasty, Pain, Multimodal analgesia, Range of motion