The Effect of Continuous Femoral Nerve Block With Modulation of Depth of Anesthesia on Prognosis of Patients Receiving Total Knee Arthroplasty

Study Overview
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Brief Summary
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The interaction of analgesia and sedation ot their effect on the prognosis of surgical patients still need to be elucidated.Currently, how to optimize intra-operative Analgesia and sedation to improve the prognosis of surgical patients is still a mystery.Intra-operative nerve block provided regional analgesia of the operated knee, which reduced the dosages of sedatives and analgesics.Based on a pilot study,the investigators found a decrease of post-operative adverse composite outcomes with the use of continuous femoral nerve block (2% versus 7%) ,therefore, the investigators postulate that general analgesia with lighter sedation in combination with peripheral nerve block could reduce the post-operative morbidity compared with deeper sedation.This randomized controlled trial is designed to test this hypothesis in patients receiving unilateral knee arthroplasty.

Detailed Description
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This study was approved by the institutional review board of the First Affiliated Hospital of Chongqing Medical University. The protocol design is in accordance with Consolidated Standards of Reporting Trials (CONSORT) statement.This study is designed as a randomized controlled trial to compare intra-operative continuous femoral nerve block combined with lighter anesthetic depth (group L) with deeper anesthetic depth (group D) monitored by bispectral index (BIS). All potentially eligible participants will be asked to give written informed consent before they are enrolled in this study.The following outcomes will be assessed:post-operative major complications (post-operative pulmonary infection,need of mechanical respiratory support,myocardio-infarction,deep venous thrombosis, pulmonary embolism, stroke, poor wound healing,all-cause post-operative death within 30 days).Secondary Outcomes included :acute post-operative pain assessed by visual analogue scale and dosages of rescue medications;Dosages of intra-operative vasopressors,anesthetics and analgesics;Life quality measured by EQ-5D questionnaire 3 months post-operatively;adverse events associated with the femoral catheter (displacement, infection, hematoma,drop-out of catheter).

Official Title
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The Effect of Continuous Femoral Nerve Block With Modulation of Depth of Anesthesia on Prognosis of Patients Receiving Total Knee Arthroplasty

Conditions
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Pain Management, Sedation, Peripheral Nerve Block, Total Knee Arthroplasty

Intervention / Treatment
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* Procedure: peri-operative continuous femoral nerve block with light sedation
* Procedure: post-operative continuous femoral nerve block
* Drug: lidocaine
* Device: ultrasound
* Device: insulated needle (Contiplex B Braun, Melsungen, Germany)
* Drug: ropivacaine
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women over the 18 years and younger than 80 years old Scheduled to receive selective unilateral knee replacement. Exclusion Criteria: Bilateral knee replacement The secondary knee revision and knee surgery not interfering with articular joint cavity (wound debridement and suture) American Society of Anesthesiology (ASA) classification of anesthesia risk IV and V grade Body mass index higher than 35 Coagulation dysfunction, which is assessed by activated partial thromboplastin time (APTT) higher than the upper limit by 10s; prothrombin time (PT) higher than the upper limit by 5s; International Normalized Ratio (INR) higher than 1.3, or any of criteria met above; Pre-operative hypoxia (SpO2< 90% or PO2<60 mmHg) Pre-operative hypercapnia (PCO2> 50 mmHg) Local infection of puncture sites Neurological diseases and pre-operative psychological disorders Uncontrolled general infection Intra-operative cardiac arrest.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group L<br>Participants in group L will receive a single injection for femoral nerve block combined with continuous femoral nerve block intra-operatively. The femoral nerve block will be performed before the induction of anesthesia on the leg to be operated. Then the patients were given the 2% lidocaine 10 ml and 1% ropivacaine 10 ml as initial dose,then,the patients will receive a continuous infusion of 0.15% ropivacaine at 15 ml/h.Intra-operatively, bispectral index score (BIS) was titrated with the adjusting of desflurane to maintain the index between 50-60.After the surgery,these patients will receive continuous femoral nerve analgesia till 3 days post-operatively( the loading dose was set at 5 ml of 0.15% ropivacaine followed by an infusion of 0.15% ropivacaine at 5 ml/h, with bolus of 5 ml and the lock time of 30 min). | Procedure: peri-operative continuous femoral nerve block with light sedation<br>* this technique will be administered to participants in group L .The puncture site was identified using ultrasound guidance (2 cm distal to the inguinal ligament, and 1 ～2 cm lateral to the femoral artery).2% lidocaine was used for topical anesthesia, then an insulated needle (Contiplex B Braun, Melsungen, Germany) (20 G*45 mm，short bevel，30°) was connected to the nerve stimulator（Innervator，Fisher &Paykel，New Zealand）.The parameters were as follows: stimulating intensity of 1 mA at a rate of 2 Hz. The needle was advanced at 30°～45° angle to the skin, until quadriceps femoral muscle twitches were elicited. Its position was accepted if contractions were still elicited when an output equal to 0.3 mA.The participants will receive continuous femoral nerve block intra-operatively and post-operatively till 3 days post-operatively.The depth of anesthesia will modulated at 50-60 with BIS monitoring<br>Drug: lidocaine<br> <br> Device: ultrasound<br> <br> Device: insulated needle (Contiplex B Braun, Melsungen, Germany)<br> <br> Drug: ropivacaine<br> <br> |
| Sham Comparator: Group D<br>Participants in group D will receive the placement of femoral nerve catheter preoperatively. The same dose of 0.9% saline was injected and infused as group L intra-operatively. Bispectral index score (BIS) was titrated with the adjusting of desflurane to maintain the index between 30-40.After the surgery,these patients will receive continuous femoral nerve analgesia till 3 days post-operatively( the loading dose was set at 5 ml of 0.15% ropivacaine followed by an infusion of 0.15% ropivacaine at 5 ml/h, with bolus of 5 ml and the lock time of 30 min). | Procedure: post-operative continuous femoral nerve block<br>* this technique will be administered to participants in group D .The puncture site was identified using ultrasound guidance (2 cm distal to the inguinal ligament, and 1 ～2 cm lateral to the femoral artery).2% lidocaine was used for topical anesthesia, then an insulated needle (Contiplex B Braun, Melsungen, Germany) (20 G*45 mm，short bevel，30°) was connected to the nerve stimulator（Innervator，Fisher &Paykel，New Zealand）.The parameters were as follows: stimulating intensity of 1 mA at a rate of 2 Hz. The needle was advanced at 30°～45° angle to the skin, until quadriceps femoral muscle twitches were elicited. Its position was accepted if contractions were still elicited when an output equal to 0.3 mA.The participants will receive continuous femoral nerve block post-operatively till 3 days post-operatively.The depth of anesthesia will modulated at 30-40 with BIS monitoring<br>Device: ultrasound<br> <br> Drug: ropivacaine<br> <br> Drug: saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major post-operative complications | Major post-operative complications summed the incidence of major complications post-operatively( (post-operative pulmonary infection,need of mechanical respiratory support,myocardio-infarction,deep venous thrombosis, pulmonary embolism, stroke, poor wound healing,all-cause post-operative death within 30 days),participants with at least one episode of the complications will be calculated as participants with complications,both the number of participants and number of events will be calculated. | From the end of surgery to 30 days post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute post-operative Pain assessed by visual analogue scale | Acute | At 12 hours ,24hours ,48hours,72 hours post-operatively | 
| Dosages of rescue medications (mg) | the dosages of tramadol,pethidine and Parecoxib during the use of patient controlled analgesia (PCA) post-operatively | From the end of surgery to 3 days post-operatively | 
| Dosages of intra-operative vasopressors,anesthetics and analgesics |  | during the surgery | 
| Life quality measured by euro-quality-5 dimensions (EQ-5D) | EQ-5D is a commonly used scale for calibration of life quality | 3 months post-operatively | 
| Adverse events associated with the femoral catheter | local infection,hematoma,drop-out of the catheter,nerve injury | From the insertion of the catheter to 3 days post-operatively |