the Efficiency of Periarticular Multimodal Drug Injection in Pain Management Following Primary Unilateral TKA

Study Overview
=================
Brief Summary
-----------------
This interventional study aims to compare the effectiveness of local multimodal drug periarticular injection in TKA patients with the standard pain control regime that includes opioids, NSAIDs, and other analgesics. The main questions The investigators strive to answer are: Is there a significant difference in the severity of pain and functional outcomes when applying periarticular injections? Are there any increased complications when applying the periarticular injections?

Detailed Description
-----------------
The best pain control regime following TKA is controversial. While opioids have an excellent analgesic effect, they also have many side effects. The investigators are conducting a randomized controlled trial to compare the severity of pain following primary unilateral TKA when multimodal drug periarticular injunction is used with the standard pain control regime. The investigators will enroll patients undergoing primary unilateral TKA and randomly allocate them into one treatment group. The first will undergo the procedure with periarticular injection before the closure is composed of a mixture of 20ml of low body weight bupivacaine 5mg/ml plus 1ml of ketorolac 30mg/ml plus 0.5ml adrenaline 1mg/ml injected in medial and lateral retinaculum, medial and lateral collateral ligaments, quadriceps and patellar tendon, joint capsule, subcutaneous fat, and the second will go standard TKA with pain control using opioids, NSAIDS, and paracetamol. The severity of postoperative pain is the primary outcome studied, as well as preoperative complications and any drug side effects, the data will be collected by a fellow researcher who is blinded to the interventions, and the patients will be blinded too. Randomization will be done by a research fellow who is not involved in patient treatment or care.

Official Title
-----------------
The Efficiency of Periarticular Multimodal Drug Injection in Pain Management Following Primary Unilateral Total Knee Arthroplasty: a Randomized Controlled Trial

Conditions
-----------------
Arthritis Knee, Pain, Arthroplasty Complications

Intervention / Treatment
-----------------
* Procedure: primary unilateral TKA
* Drug: Bupivacain
* Drug: ketorolac
* Drug: epinephrine
* Drug: Paracetamol
* Drug: Ketorolac
* Drug: Tramadol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: all patients with end-stage arthritis of the knee going primary unilateral total knee arthroplasty. Exclusion Criteria: inflammatory and secondary arthritis of the knee. Patients who are allergic to one or more of the drugs used in the injections. Patients who are already taking opioids for whatever reason or have a history of addiction. BMI less than 20 and more than 35. patients with intra-operative complications that would affect the outcomes measurement. Patients who are going through complex primary or revision TKA. Pregnancy, renal or liver failure. Patients who are classified as grade 3 or more according to ASA.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TKA with pain management by multimodal periarticular injection.<br>Patients going TKA and getting an injection of a mixture of 20ml of low body weight bupivacaine 5mg/ml plus 1ml of ketorolac 30mg/ml plus 0.5ml adrenaline 1mg/ml injected in medial and lateral retinaculum, medial and lateral collateral ligaments, quadriceps and patellar tendon, joint capsule, subcutaneous fat before closure. | Procedure: primary unilateral TKA<br>* Primary unilateral total knee arthroplasty with cruciate scarifying cemented DePuy Synthes PFC Sigma prosthesis.<br>Drug: Bupivacain<br>* low body weight (0.50%, 20cc) intraoperative periarticular injection<br>Drug: ketorolac<br>* 1ml of 30mg/ml ketorolac intraoperative periarticular injection<br>* Other names: Toradol;Drug: epinephrine<br>* 0.5ml Adrenaline 1mg/ml intraoperative periarticular injection<br>* Other names: Adrenaline;Drug: Tramadol<br>* IV Tramadol [Ultram] introduced when needed after surgery<br>|
| Experimental: TKA with pain management by IV/oral analgesics.<br>Patients going TKA and getting a standard pain control regime of IV opioids when needed, IV ketorolac, and IV/oral paracetamol. | Procedure: primary unilateral TKA<br>* Primary unilateral total knee arthroplasty with cruciate scarifying cemented DePuy Synthes PFC Sigma prosthesis.<br>Drug: Paracetamol<br>* IV Paracetamol [Ofirmev] introduced every 6 hours after surgery<br>Drug: Ketorolac<br>* IV Ketorolac {Toradol} introduced every 12 hours after surgery.<br>Drug: Tramadol<br>* IV Tramadol [Ultram] introduced when needed after surgery<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| perception of pain - first assessment | The severity of knee pain in the short postoperative period. As stated by the patient, on a scale of 0 to 10, 0 resents no pain at all, and 10 is the worst pain the participant can imagine. | measured 12 hours after surgery. | 
| perception of pain - second assessment | The severity of knee pain in the short postoperative period. As stated by the patient, on a scale of 0 to 10, 0 resents no pain at all, and 10 is the worst pain the participant can imagine. | measured 24 hours after surgery. | 
| perception of pain - third assessment | The severity of knee pain in the short postoperative period. As stated by the patient, on a scale of 0 to 10, 0 resents no pain at all, and 10 is the worst pain the participant can imagine. | measured 48 hours after surgery. | 
| functional status - first assessment | a Knee Score section (7 items) and a Functional Score section (3 items). Both sections are scored from 0 to 100 with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions. here, the investigator assesses the function section. | first measurement four weeks after surgery. | 
| magnitude of disabling pain according to KSS - first assessment | a Knee Score section (7 items) and a Functional Score section (3 items). Both sections are scored from 0 to 100, with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions. Here the investigator assesses the pain section. | first measurement four weeks after surgery. | 
| magnitude of disabling pain according to KSS - second assessment | a Knee Score section (7 items) and a Functional Score section (3 items). Both sections are scored from 0 to 100, with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions. Here the investigator assesses the pain section. | first measurement six months after surgery. | 
| functional status - second assessment | a Knee Score section (7 items) and a Functional Score section (3 items). Both sections are scored from 0 to 100 with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions. here, the investigator assesses the function section. | second measurement six months after surgery. | 
| estimated total blood loss | the total amount of lost blood in the perioperative period and will be calculated using the Gross formula which is estimated by hitting the patients' blood volume by the difference between pre and post-operative hematocrit value divided by the initial hematocrit value | measured once 48 hours after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| perioperative complications | complications such as Venous thromboembolism VTE, infection, drug side effects ETC | if happened within 6 months of surgery | 
| opioids consumption - frequency | the amount of consumed opioids measured by times of application in the close postoperative period | measured once 48 hours after surgery. | 
| opioids consumption - dose | the amount of consumed opioids measured by the dose used in the close postoperative period | measured once 48 hours after surgery. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pain, arthritis, injection, total knee arthroplasty