Clinical trial NCT03706313
Conditions: Post-operative Pain
Keywords: Total knee replacement
Sponsor: Duke University
Start date: 2019-01-15; Completion date: 2019-10-22
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study seeks to examine the analgesic efficacy of genicular nerve blocks for pain after total knee replacement.

Detailed description:
Part of the way in which pain is controlled during total knee replacement surgery is through a nerve block. The investigators have developed an effective protocol for pain control after knee replacement, but know that many patients still experience pain around the knee after knee replacement. There are nerves around the knee that carry pain impulses from behind the knee. The investigators believe that placing numbing medicine around these nerves can help with pain in front of the knee after surgery, in addition to the standard nerve block placed for knee replacement surgery. This may result in taking less pain medication by mouth,and having less pain with movement. For this study, before the operation, either a placebo solution or the local anesthetic bupivacaine (a numbing solution) will be placed at three sites around the knee where these nerves reside. The investigators will evaluate how participants feel in recovery after surgery, during the stay in the hospital, and call at home one week after surgery. Knowing if numbing these nerves helps with pain after surgery will help us further refine our postoperative care plan for patients.

Arms: arm 1: The ultrasound-guided genicular nerve block will be performed at the site of the superior lateral, the superior medial, and the inferior medial genicular nerves. Color Doppler will be used to identify the arterial structures which serve as landmarks for the corresponding nerves.

After skin local anesthetic infiltration, a 10 cm 21G insulated block needle will be inserted and aligned with the ultrasound scanning plane. Once satisfactory position of the needle is confirmed, 5mL of a solution containing 15 ml 0.25% bupivacaine with 2mg dexamethasone or 5mL saline will be slowly injected. Spread of local anesthetic will be documented adjacent to the target nerve. This procedure will be performed at the site of the three genicular nerves described. arm 2: The ultrasound-guided genicular nerve block will be performed at the site of the superior lateral, the superior medial, and the inferior medial genicular nerves. Color Doppler will be used to identify the arterial structures which serve as landmarks for the corresponding nerves.

After skin local anesthetic infiltration, a 10 cm 21G insulated block needle will be inserted and aligned with the ultrasound scanning plane (in-plane approach). Once satisfactory position of the needle time is confirmed, 5mL of a saline will be slowly injected. Spread of local anesthetic will be documented adjacent to the target nerve. This procedure will be performed at the site of the three genicular nerves described.
Interventions: intervention 1: 15mL 0.25% bupivacaine intervention 2: Genicular nerve block intervention 3: Saline
Intervention descriptions: intervention 1: Patients will be randomly assigned to either a genicular nerve block with bupivacaine or saline intervention 2: The ultrasound-guided genicular nerve block will be performed at the site of the superior lateral, the superior medial, and the inferior medial genicular nerves. Color Doppler will be used to identify the arterial structures which serve as landmarks for the corresponding nerves.

After skin local anesthetic infiltration, a 10 cm 21G insulated block needle will be inserted and aligned with the ultrasound scanning plane. Once satisfactory position of the needle is confirmed, 5mL of a solution containing 15 ml of 0.25% bupivacaine with 2mg dexamethasone or 5mL saline will be slowly injected. Spread of local anesthetic will be documented adjacent to the target nerve. This procedure will be performed at the site of the three genicular nerves described. intervention 3: Patients will be randomly assigned to either a genicular nerve block with bupivacaine or saline

Protocol documents:
Prot_SAP_000.pdf: 
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1. Protocol Title 
A comparison of analgesic efficacy of ultrasound-guided genicular nerve block versus 
saline injection for total knee replacement: a prospective, randomized controlled trial. 
 
Milly Rambhia, Jeff Gadsden 
 
2. Purpose of the study 
To determine if ultrasound-guided genicular nerve blocks with 0.25% bupivacaine and 
dexamethasone provide improved knee analgesia for patients recovering from primary 
total knee replacement surgery compared to saline injection. 
 
3. Background and Significance 
 
Total knee arthroplasty is associated with intense early postoperative pain. A sizeable 
proportion (25–40%) of patients experience severe pain postoperatively despite a 
comprehensive multimodal analgesic regimen.(1) Enhanced recovery protocols that 
emphasize early mobilization and hospital discharge remain varied among hospitals. 
Regional anesthetic techniques have evolved to preserve motor function in an effort to 
promote early ambulation and hospital discharge, while optimizing sensory blockade for 
adequate analgesia. The adductor canal blockade (ACB) of the saphenous nerve has 
demonstrated reduced opioid consumption and preservation of quadriceps muscle 
strength when compared to placebo and to femoral nerve blockade.(2) However, several 
studies have shown that despite ACB, many patients may still have at least moderate, 
movement-related pain. This may be partly because the ACB does not provide analgesia 
to the posterior aspect of the knee, in which pain is commonly moderate to severe after 
surgery. 
 
It has been proposed in the literature that complete blockade of the knee joint for 
adequate analgesia requires blockade of the genicular nerves.(3) The genicular nerves 
provide sensory innervation to the joint capsule and internal and external ligaments of 
the knee joint. The superior and inferior medial genicular nerves arise in the posterior 
popliteal fossa and are sensory branches of the tibial nerve. The superior and inferior 
lateral genicular nerves are sensory branches of the common peroneal nerve and 
course anteriorly to the lateral knee. The identification of the genicular nerves using 
ultrasound has been described in the literature.(4) 
 
At our institution, all patients scheduled to undergo total knee replacement spinal 
anesthesia as well as infiltration of local anesthetic into the Interspace between the 
Popliteal Artery and posterior Capsule of the Knee (IPACK) injections as part of their 
pain management, as this practice provides analgesia while preserving motor 
function.(5)1 Postoperatively, all patients receive adductor canal peripheral nerve 
catheters. 
 


We hypothesize that the combination of ultrasound-guided adductor canal nerve 
catheter, IPACK block, and singe injection genicular nerve blockade will further decrease 
opioid consumption and pain scores, therefore leading to decreased systemic side 
effects and improved overall satisfaction compared to ultrasound-guided adductor canal 
catheter and IPACK block alone in patients undergoing elective minimally invasive TKA 
surgery.   
 
4. Design and Procedures 
This is a single center, prospective, randomized, controlled, single-blinded study. 40 
subjects will be recruited (see #6 Recruitment and Compensation below), 20 in each 
group.  
 
Primary Outcome: 
Cumulative opioid consumption at 24 hours. 
       
 
Secondary Outcomes: 
• Quality of analgesia at rest and with movement, as measured by numerical pain 
rating scores (NRS-11) up to 48 hours (0h, 6h, 24h, 36h, 48h)  
• Cumulative opioid consumption at 48 hours  
• Opioid consumption and quality of analgesia based on patient diary after discharge 
on postoperative day 7 (worst pain score) 
• Sleep quality based on number of times awakened on the evening of POD#0 
• Subject satisfaction with the block technique at 24h and POD#7  
• 20 meter walk test time on POD#1. This will be conducted on 6100, the orthopedic 
floor. Research staff will conduct the test, which will involve the patient walking at 
his/her fastest pace to a mark on the floor 10m away, then turning around and 
returning to the start line.  
 
Preoperative Management 
Subjects will be randomized on the morning of surgery to receive either genicular nerve 
blocks using 15mL 0.25% bupivacaine with 2mg dexamethasone or the same blocks 
with 15 ml of saline.  
 
Prior to the block in the preoperative holding area, all subjects will receive the standard 
oral multimodal analgesic regimen, a spinal anesthetic with 12.5 mg of bupivacaine, and 
posterior capsule infiltration with 20 ml of 0.2% ropivacaine. Subjects will then receive 
the study intervention. 
 
Single injection genicular nerve block technique 
 
The ultrasound-guided genicular nerve block will be performed at the site of the superior 
lateral, the superior medial, and the inferior medial genicular nerves. The superior lateral 
genicular nerved is located at the confluence of the lateral femoral shaft and the lateral 
femoral condyle (in the anteroposterior plane) and at the midpoint of the femur (in the 


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lateral plane). The superior medial genicular nerve site is located at the confluence of 
the medial femoral shaft and the medial femoral condyle (in the anteroposterior plane) 
and at the midpoint of the femur (in the lateral plane). The inferior medial genicular nerve 
site was located at the confluence of the medial tibial shaft and the tibial flare (in the 
anteroposterior plane) and the midpoint of the tibia (in the lateral plane). Color Doppler 
will be used to identify the arterial structures which serve as landmarks for the 
corresponding nerves. All nerve blocks will be performed by a trainee supervised by an 
anesthesiologist experienced in regional anesthesia. 
 
After skin local anesthetic infiltration, a 10 cm 21G insulated block needle (Sonoplex, 
Pajunk Medical Systems, Norcross, GA) will be inserted from the lateral aspect of the 
ultrasound probe and aligned with the ultrasound scanning plane (in-plane approach). In 
this way, both the needle shaft and tip can be visualized as the needle approaches the 
genicular nerve. The needle will be redirected as needed. Once satisfactory position of 
the needle time is confirmed and after frequent negative aspiration, 5mL of a solution 
containing 15 ml of 0.25% bupivacaine with 2mg dexamethasone, or 5mL saline, will be 
slowly injected. Spread of local anesthetic will be documented adjacent to the target 
nerve in real time. This procedure will be performed at the site of the three genicular 
nerves described above. 
 
Subjects will then undergo the surgical procedure. In the post-anesthesia care unit 
(PACU), all subjects will receive the standard adductor canal continuous catheter that 
will be connected to a pump containing 0.2% ropivacaine with infusion rate of 8mL/hr. 
 
Intraoperative Management  
Subjects will receive a spinal anesthetic using intravenous propofol infusion for sedation. 
No muscle relaxation will be permitted. In addition, no long-acting opioids will be 
administered for analgesia; instead, boluses of fentanyl 25 to 50 mcg will 
be administered as guided by respiratory parameters and/or hemodynamics. Subjects 
will maintain spontaneous ventilation throughout surgery. Respiratory rate greater than 
18 per minute will be treated by administration of 25 to 50 mcg of fentanyl. At the 
conclusion of the case, the propofol will be discontinued and the subject awakened. 
Subjects will be transported to PACU. All subjects will receive intravenous fentanyl 
and/or oral oxycodone as needed for pain management.  
 
Postoperative Evaluation 
Evaluation of both pain intensity (NRS-11 pain scale) and interval opioid consumption 
will be undertaken at the following time points in a blinded fashion by a member of the 
research team: 
• PACU (30-60 minutes after arrival to PACU) 
• 6 hours postoperatively 
• 24 hours postoperatively 


• 36 hours postoperatively 
• 48 hours postoperatively 
• POD 7 (morning of POD#7) 
All data will be recorded in a REDCap database. Subjects will be provided with a diary to 
record the relevant data elements. Calls will be made on POD 7 to record the data in the 
research record by a member of the research team.  
Sleep quality will also be assessed by a member of the research team on POD#1 as a 
function of the number of times the patient was awoken by pain. 
Occurrences of adverse events reported by subjects will also be collected during the 
phone interview on POD#7. Subjects will be queried as to any block related 
complications (e.g., prolonged motor blockade or numbness) and opioid-related adverse 
events. Satisfaction with the postoperative pain management experience will also be 
graded on a 0-10 point scale on POD#7. 
 
5. Selection of subjects 
Criteria for inclusion: 
• 
Subjects scheduled for primary elective total knee arthroplasty 
• 
Age 56-85 years of age 
• 
American Society of Anesthesiologists Physical Status I-III 
• 
BMI 18-40 kg/m2 
 
Criteria for exclusion: 
• 
Inability to cooperate with protocol 
• 
Inability to understand or speak English 
• 
Allergy to ropivacaine, bupivacaine or other local anesthetic 
• 
Contraindication to peripheral nerve block (e.g. local infection, neurologic deficit 
or disorder, previous trauma or surgery to ipsilateral knee, etc.) 
• 
Revision knee surgery 
• 
Chronic opioid consumption (daily morphine equivalent of >30 mg for at least four 
weeks prior to surgery) 
• 
History of chronic pain 
• 
History of psychiatric disorder 
• 
History of diabetes mellitus with documented or symptomatic peripheral 
neuropathy 
 
6. Subject recruitment and compensation 
Potential subjects (see inclusion criteria above) will be identified on the surgical schedule 
several days in advance of the surgical procedure. These individuals will be contacted 
by telephone and asked for permission to discuss the study. The purpose of the study 
will be explained, the consent form read out loud, and any questions answered. Potential 
subjects will be encouraged to take time to discuss the study with family, and will be told 


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that there will be additional time to answer any questions on the day of surgery. Potential 
subjects will be told that there is no obligation to take part in the study and their decision 
will not affect the quality of their care.  
On the day of surgery, one of the investigators will approach the potential subject in the 
preoperative area and answer any remaining questions. Subjects that indicate their 
interest in participating will then sign an informed consent and complete a HIPAA 
authorization form. There will be no compensation for subjects for their participation.  
 
7. Consent process 
The consent process will be conducted by one of the physician investigators involved in 
the study. The consent process will take place in the pre-operative area. Throughout the 
consent process, measures will be taken to maintain privacy, such as conducting face-
to-face conversations in private rooms. As much time as necessary will be spent with 
each potential subject to sufficiently explain and answer all questions, and address all 
concerns they may have in regard to the study and/or consent process. 
 
8. Subject’s Capacity to Give Legally Effective Consent 
Subjects who do not have the capacity to give legal consent will not be approached for 
participation in this study. 
 
9. Study interventions 
See #4. 
 
10. Risk/benefit assessment 
Risk to the subject 
This study involves a single injection genicular nerve block, either with a local anesthetic 
solution or saline. Risks associated with the nerve block include bleeding, infection, and 
nerve damage. 
 
Benefits to the subject 
There are no direct benefits to the subject. There is potential for improved pain control if 
the subject is randomized to the treatment arm.  
 
11. Costs 
There will be no costs to the subject for participation in the study. Subjects will not be 
compensated for their participation. 
 
12. Data analysis and statistical considerations 
Based on our institutional experience with primary total knee arthroplasty and 
postoperative opioid consumption, we calculate that 20 patients per group (total of 40) 
will be required to detect a 30% difference in our primary outcome measure. 
 
Baseline patient demographic and clinical characteristics as well as surgical factors will 
be compared between treatment groups.  The difference in the primary outcome, 24h 


opioid consumption, will be assessed via two-sided two-sample t-test.  Outcome data 
distribution will be assessed for normality and log-transformed if necessary. If 
differences in key patient factors are identified between groups we will pursue a 
multivariable linear model in order to control for potential confounding of treatment effect 
estimates. Secondary numeric outcomes of pain score and opioid consumption at 48 
hours and post-op day 7 will be compared via t-tests or Mann-Whitney tests as 
appropriate. Sleep quality during the night of surgery will be assessed via poisson 
regression of the count of times awakened from sleep.  Subject satisfaction with the 
block technique will be compared using a t-test or Mann-Whitney test as appropriate. 
 
13. Data & Safety Monitoring 
In accordance with federal regulations the PI will monitor for, review, and promptly report 
to the IRB, appropriate institutional officials, sponsor, coordinating center and the 
appropriate regulatory agency head all unanticipated problems involving risks to subjects 
or others that occur in the course of a subject’s participation in a research study (45 CFR 
46.103(b)(5)(i) and 21 CFR 56.108(b)(1)), all AE reports will be reported per the DUHS 
IRB policies. PI will be monitoring all AEs and submitting reports to the IRB per DUHS 
IRB policy. 
 
14. Privacy, Data Storage and Confidentiality 
Potential subjects and their families will be approached in private rooms. Any guests not 
involved in the consent process will be asked to leave the room during any 
communications, unless the subject allows them to be present. Efforts to maintain 
subject confidentiality will include assignment of following Federal Privacy Regulations 
which provide safeguards for privacy, security, and authorized access. Except when 
required by law, subjects will not be identified by name, social security number, address, 
telephone number, or any other direct personal identifier in study records disclosed 
outside of Duke University Health System (DUHS).  Subjects will be not be revealed in 
any reports or publications resulting from this study.  For records disclosed outside of 
DUHS, subjects will be assigned a unique code number. The paper/electronic data will 
be stored as per the RDSP. 
 
 
References 
 
1. 
Grevstad U, Mathiesen O, Lind T, Dahl JB. Effect of adductor canal block on pain 
in patients with severe pain after total knee arthroplasty: A randomized study with 
individual patient analysis. Br J Anaesth 2014; 112: 912-9. 
 
2. 
Jiang X, Wang Q., Wu C, Tian W. Analgesic efficacy of adductor canal block in 
total knee arthroplasty: a meta-analysis and systematic review. Orthop Surg 2016; 8: 
294–300. 
3. 
Egeler C, Jayakumar A, Ford S. Adductor canal block is useful but does not 
achieve a complete block of the knee. Reg Anesth Pain Med. 2014; 39: 81–82. 


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4. 
Meng M, Waldman R, Waldman C, Waldman S. Ultrasound guided genicular 
nerve block-a motor sparing technique for the treatment of acute and chronic knee pain. 
Int. J. Anesthesiol. Res. 2015; 3: 37-43.  
 
5. 
Cullom C, Weed J.T. Anesthetic and Analgesic Management for Outpatient Knee 
Arthroplasty. Curr Pain Headache Rep. 2017; 21: 23.