Clinical trial NCT02826551
Conditions: Anesthesia
Sponsor: Cedars-Sinai Medical Center
Start date: 2017-01-01; Completion date: 2017-05-10
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Post-operative pain control following elective anterior cruciate ligament reconstruction continues to be a hurdle for orthopaedic surgeons. This obstacle becomes particularly problematic during the first 36 hours after the operation, when the patient is experiencing pain at its peak intensity. Good control of pain leads to better patient comfort, confidence to place weight on the operative limb and improved ability to perform critical exercises in this period to improve joint range of motion.

A variety of anesthetic techniques have been employed to reduce pain including: cryotherapy, systemic analgesic and anti-inflammatory drugs, intrathecal, regional blockade of peripheral nerves and frequently intra-articular injections. Each technique has been studied at length with mixed but overall favorable results. However, in the authors' experience, after femoral nerve blockade, patients continue to complain of posterior knee pain in the Post-Anesthesia Care Unit (PACU) and peri-operative period. Intra-articular injections comprised of morphine and other Na-channel blocker analgesics may curb some of this pain by bathing the posterior capsule in anesthetic. However, there is still a large concern amongst orthopaedic surgeons about the potential harm these agents may have on the knee's healthy articular cartilage surfaces. The long term effects, including chondrolysis have been documented in the shoulder and while in the short term this effect is diminished there is still hesitation among surgeons to use this form of pain blockade.

This has led the investigators to adapt a technique of isolated posterior capsular injections after total knee replacements from the joint arthroplasty literature, which has shown favorable results with low complication risk. The investigators plan to study the effectiveness of this technique during ACL reconstruction in an attempt to curb the amount of posterior knee pain and decrease the overall narcotic use postoperatively while limiting the exposure of the native cartilage to harmful agents.

Detailed description:
A prospective series of consecutive patients undergoing primary ACLR will be recruited from a preoperative log of patients seeing one of two sports medicine fellowship trained surgeons within the investigators group. Patients undergoing primary unilateral anterior cruciate ligament reconstruction (ACLR) either with bone-patellar bone autograft or Achilles tendon allograft will be included by surgeons using similar techniques and fixation options.

After consenting to participate, subjects will be randomized into one of two groups. Using a random number generator, 60 consecutively enrolled patients will be placed in their appropriate study arm. (Odd numbers = Control Group) (Even numbers = Experimental Group). Only the patient will be blinded to which arm of the study they belong.

Group 1(Control) patients will undergo routine arthroscopically assisted ACLR surgery with a standardized postoperative protocol. Group 2 (Experimental) patients will undergo the same procedure with the same postoperative protocols as Group 1, with the addition of the posterior capsular injection of 20 cc of Marcaine 0.5%. There are no placebo treatments being offered and the surgeons and operating room staff are not blinded to the subjects group. Injecting marcaine in this study will be performed in accordance with its standard use according to the FDA labeling/guidelines. The physicians will use their discretion as to the appropriate location for the injection into the posterior capsule of the knee which should bring no additional risks than expected for a knee injection.

At the conclusion of the case, each patient will receive a dry sterile dressing, followed by a compression wrap and a hinged knee brace locked in extension. No drains, pain pumps or nerve stimulators will be used. The nurses in the recovery room who will be administering the VAS assessment and recording time and frequency of pain medication dosing will be blinded to the patients' Group number. The nurses will provide pain medications and the visual analog assessment for their duties in the post-op anesthesia unit, and are not administering drugs or procedures specifically for research purposes.

Post-operative Care All patients will be discharged home from the surgery center on the same day (within 2-3 hours) postoperatively. Patients will be made weight bearing as tolerated with crutches and a brace.

While in the PACU, at time points 15min and 1 hour, a standardized and previously validated visual analog scale (VAS) for pain assessment will be delivered to the patient by the recovery room nurse.

Patients after discharge will then be asked to rate their most severe pain each morning and night for 4 consecutive postoperative days using this VAS pain scale. A standardized pain medication regimen will be given including: one or two tabs of Percocet 7.5/325mg to be taken every 4 to 6 hours as needed. A log of the time and amount of medication taken each POD will be kept and recorded by the patients. Patients will also be instructed to use cryotherapy for 20 min intervals 3 times per day. Patients will also begin on POD 0 the use of continuous passive motion machines starting at a comfortable range of motion and progressing 5 degrees/day as tolerated. Patients will return for their first post-operative visit between 7-10 days where diaries will be collected and the patient clinically assessed.

Patient's will also be seen at their three month post-operative visit and be clinically assessed for the presence of chondrolysis (a frequently measured outcome during knee pain medication injection studies).

Statistical Analysis Based on previous studies, the Mann-Whitney U test will check differences between numeric variables. Nonparametric Kruskal-Wallis tests can compare the analgesia level in the two groups and if possible ANOVA test can compare the analgesia duration. Chi-square tests will be utilized for any potential complications which will also be recorded.

Power Analysis Prelim Power Analysis per STATS department @ Cedars: sample sizes of 26 for each group (N1=N2=26) = Total 52 patients to achieve 80% power to reject the null hypothesis of equal means when the population mean difference is 2 with a standard deviation for both groups of 2.5 and with a significance level (alpha) of 0.050 using a two-sided two-sample equal-variance t-test. A total of 60 patients will be enrolled to ensure the investigators achieve adequate power for the study.

Despite the addition of selective regional blockade by the anesthesia team including femoral and saphenous nerve blocks, a portion of patients are still experiencing post-operative knee pain within the first few hours to days after the procedure. Pain may be a result of the femoral tunnel drilling which theoretically may be relieved by a posterior capsular injection. Eliminating this painful period will improve the patient's subjective experience undergoing surgery, and may also allow for earlier range of motion and participation in rehabilitation strengthening exercises performed by the patient in the peri-operative period.

Arms: arm 1: These patients will receive standard of care when undergoing anterior cruciate ligament reconstruction and will NOT be receiving a posterior capsular knee injection of Marcaine 0.5%.

They will be monitored for pain control and pill intake while in the PACU and the first four days post-operatively the same as the patients in the INJECTION Arm of the study. arm 2: These patients will receive standard of care when undergoing anterior cruciate ligament reconstruction but will additionally be receiving a one-time posterior capsular knee injection of Marcaine 0.5% (20cc) during the surgery.

They will be monitored for pain control and pill intake while in the PACU and the first four days post-operatively the same as the patients in the NO injection Arm of the study.
Interventions: intervention 1: Marcaine intervention 2: Ice intervention 3: Percocet intervention 4: Knee Brace and Crutches
Intervention descriptions: intervention 1: Pain control medication to theoretically reduce the amount of posterior knee pain that is common after ACL surgery by placing the injection into the posterior capsule of the knee during surgery. This is very easy and safe to accomplish as the surgeon will have direct visualization of the posterior capsule during the surgery. intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_000.pdf: 
 
 
PROJECT TITLE 
 
Pain outcomes after posterior capsular injection during Anterior 
Cruciate Ligament (ACL) reconstruction: A prospective, 
randomized trial. 
 
BACKGROUND and 
RELEVENT 
REFERENCES 
 
 
Post-operative pain control following elective anterior cruciate ligament 
reconstruction continues to be a hurdle for orthopaedic surgeons. This 
obstacle becomes particularly problematic during the first 36 hours after the 
operation, when the patient is experiencing pain at its peak intensity. Good 
control of pain leads to better patient comfort, confidence to place weight on 
the operative limb and improved ability to perform critical exercises in this 
period to improve joint range of motion. (Rev Bras Ortop. 2015 Jun 16;50(3):300-4)  
 
A variety of anesthetic techniques have been employed to reduce pain 
including: cryotherapy, systemic analgesic and anti-inflammatory drugs, 
intrathecal, regional blockade of peripheral nerves and frequently intra-
articular injections. Each technique has been studied at length with mixed but 
overall favorable results. However, in the authors’ experience, after femoral 
nerve blockade, patients continue to complain of posterior knee pain in the 
Post-Anesthesia Care Unit (PACU) and peri-operative period. Intra-articular 
injections comprised of morphine and other Na-channel blocker analgesics 
may curb some of this pain by bathing the posterior capsule in anesthetic. 
However, there is still a large concern amongst orthopaedic surgeons about 
the potential harm these agents may have on the knee’s healthy articular 
cartilage surfaces. The long term effects, including chondrolysis have been 
documented in the shoulder and while in the short term this effect is 
diminished there is still hesitation among surgeons to use this form of pain 
blockade.  
 
This has led the authors to adapt a technique of isolated posterior capsular 
injections after total knee replacements from the joint arthroplasty literature, 
which has shown favorable results with low complication risk. (Orthop Clin North 
Am. 2015 Jan;46(1):1-8). We plan to study the effectiveness of this technique 
during ACL reconstruction in an attempt to curb the amount of posterior knee 
pain and decrease the overall narcotic use postoperatively while limiting the 
exposure of the native cartilage to harmful agents.  
 
References: See Attached Sheet 
OBJECTIVE 
 
To determine if there is a significant difference in post-operative 
pain visual analog pain (VAS) scores, a decrease in time before 
first narcotic and total decrease in peri-operative narcotic use 
after ACL bone-patellar-bone reconstruction after a posterior 
capsular injection with 20cc of 0.5% marcaine.  
 


SITE/RESOURCES 
Please list location 
where study will be 
carried out and any 
staffing resources 
that will be needed. 
Indicate if site/staff 
have committed to 
project or if they 
have been 
approached 
Kerlan Jobe Orthopaedic Clinic 
 
Post-Anesthesia Care Unit Nursing staff: if the fellow is 
unavailable they will deliver the visual analog pain scale survey 
to patients at specific time points. – Staff has been instructed on 
how to administer the surveys appropriately. 
 
Anesthesia- We have discussed with the anesthesia staff that the 
femoral nerve blocks will be standardized for all patients in the 
study.  
 
Statistician – Cedars STATs department has been contacted 
METHODOLOGY 
To include: 
-hypothesis 
- variables 
- methods 
-statistical analysis 
plan 
- power analysis 
 
 
Hypothesis: Patients who receive a posterior capsular injection with Marcaine 
0.5% during ACLR will report less pain and have less total narcotic use 
immediately post-op and up 4 days postoperatively compared to those that 
did not receive this injection. 
 
Variables 
1) Injection Group 
a. VAS Scores @ 15min/1 hour/POD1- 4 
b. Time to first narcotic 
c. 
Total narcotic use 
d. 3 month Post-op visit assessment ((rule out chondrolysis) 
2) Non-Injection Group 
a. VAS Scores @ 15min/1 hour/POD 1-4 
b. Time to first narcotic 
c. 
Total narcotic use 
d. 3 month Post-op visit assessment (rule out chondrolysis) 
Methods 
A prospective series of consecutive patients undergoing primary ACLR will be 
recruited from a preoperative log of patients seeing one of four sports 
medicine fellowship trained surgeons within our group. Patients undergoing 
primary unilateral anterior cruciate ligament reconstruction (ACLR) either 
with bone-patellar bone autograft or Achilles tendon allograft will be included 
by surgeons using similar techniques and fixation options.  
 
Inclusion Criteria – Adult individuals (ages 18-60), both sexes, submitted to 
elective ACL reconstructions with or without partial menisectomies of the 
medial or lateral meniscus. 
 
Exclusion Criteria – 1) Multiligamentous injury or revision surgery 2) Known 
narcotic/substance abuse or regular opiate use 3) Known allergy to any 
medication or anesthetic being used in this study 4) Patients with pre-existing 
diabetic or femoral neropathy 5) INTRAOPERATIVELY- if chrondral 
microfractures, inside-out or outside-in meniscal repairs were performed 
(***Since these additional surgeries within the joint may increase the 
perceived level of pain post-op***)  
 
After consenting to participate, subjects will be randomized into one of two 
groups. Using a random number generator, 


http://stattrek.com/statistics/random-number-generator.aspx 
60 consecutively enrolled patients will be placed in their appropriate study 
arm. (Odd numbers = Control Group) (Even numbers = Experimental Group). 
Only the patient will be blinded to which arm of the study they belong.  
 
Group 1(Control) patients will undergo routine arthroscopically assisted ACLR 
surgery with a standardized postoperative protocol. Group 2 (Experimental) 
patients will undergo the same procedure with the same postoperative 
protocols as Group 1, with the addition of the posterior capsular injection of 
20 cc of Marcaine 0.5%. There are no placebo treatments being offered and 
the surgeons and operating room staff are not blinded to the subjects group. 
Injecting marcaine in this study will be performed in accordance with its 
standard use according to the FDA labeling/guidelines. The physicians will use 
their discretion as to the appropriate location for the injection into the 
posterior capsule of the knee which should bring no additional risks than 
expected for a knee injection. 
 
At the conclusion of the case, each patient will receive a dry sterile dressing, 
followed by a compressive wrap and a hinged knee brace locked in extension. 
No drains, pain pumps or nerve stimulators will be used. The nurses in the 
recovery room who will be administering the VAS assessment and recording 
time and frequency of pain medication dosing will be blinded to the patients’ 
Group number. The nurses will provide pain medications and the visual analog 
assessment for their duties in the post-op anesthesia unit, and are not 
administering drugs or procedures specifically for research purposes. 
 
Post-operative Care 
All patients will be discharged home from the surgery center on the same day 
(within 2-3 hours) postoperatively. Patients will be made weight bearing as 
tolerated with crutches and a brace.  
 
While in the PACU, at time points 15min and 1 hour, a standardized and 
previously validated visual analog scale (VAS) for pain assessment will be 
delivered to the patient by the recovery room nurse. In addition, during this 
time, the extent of postoperative motor block will be assessed using the 
Bromage scale as follows: 0 = free movement of the leg/foot, 1 = Free foot 
movement with only knee flexion 2 = Free foot movement with inability to 
flex knee and 3 = complete motor blockade of knee and foot. 
 
Patients after discharge will then be asked to rate their most severe pain each 
morning and night for 4 consecutive postoperative days using this VAS pain 
scale. A standardized pain medication regimen will be given including: one or 
two tabs of Percocet 7.5/325mg to be taken every 4 to 6 hours as needed. A 
log of the time and amount of medication taken each POD will be kept and 
recorded by the patients. Patients will also be instructed to use cryotherapy 
for 20 min intervals 3 times per day. Patients will also begin on POD 0 the use 
of continuous passive motion machines starting at a comfortable range of 
motion and progressing 5 degrees/day as tolerated. Patients will return for 
their first post-operative visit between 7-10 days where diaries will be 
collected and the patient clinically assessed.  
 
Patient's will also be seen at their three month post-operative visit and be 
clinically assessed for the presence of chondrolysis (a frequently measured 


outcome during knee pain medication injection studies). 
 
Statistical Analysis 
Based on previous studies, the Mann-Whitney U test will check differences 
between numeric variables. Nonparametric Kruskal-Wallis tests can compare 
the analgesia level in the two groups and if possible ANOVA test can compare 
the analgesia duration. Chi-square tests will be utilized for any potential 
complications which will also be recorded. (J Inj Violence Res. 2013 Jun; 5(2): 84-88.) 
(Acta Ortop Bras. 2012;20(5); 285-90) 
 
Power Analysis 
Prelim Power Analysis per STATS department @ Cedars: sample sizes of 26 
for each group (N1=N2=26) = Total 52 patients to achieve 80% power to 
reject the null hypothesis of equal means when the population mean 
difference is 2 with a standard deviation for both groups of 2.5 and with a 
significance level (alpha) of 0.050 using a two-sided two-sample equal-
variance t-test. A total of 60 patients will be enrolled to ensure we achieve 
adequate power for the study. 
CLINICAL 
RELEVANCE 
IMPACT 
Despite the addition of selective regional blockade by the 
anesthesia team including femoral and saphenous nerve blocks, 
a portion of patients are still experiencing post-operative knee 
pain within the first few hours to days after the procedure. Pain 
may be a result of the femoral tunnel drilling which theoretically 
may be relieved by a posterior capsular injection. Eliminating this 
painful period will improve the patient’s subjective experience 
undergoing surgery, and may also allow for earlier range of 
motion and participation in rehabilitation strengthening 
exercises performed by the patient in the peri-operative period. 
APPROX BUDGET 
Include 
comprehensive and 
detailed budget. 
Do NOT include any 
overhead expenses 
 
Marcaine 0.5% with epi & 20 cc, syringe = Pending 
Paper VAS forms = Pending (< $100) 
Envelopes for randomization process = Pending ($<50) 
Statistician = Pending 
AUTHORS 
 
indicate areas of 
involvement 
 
 
                  
1._Michael Birns, M.D – Primary Researcher 1,2,3,4,5 
2._Michael Banffy, M.D – Principle Investigator 1,2,4 
3._Orr Limpisvasti, M.D.1,2,4 
4._Aneet Toor, M.D. 1,2,3,4,5 
 
 
1= idea development/project design; 2=data collection; 3=data analysis; 
4=data interpretation; 5=manuscript preparation/revisions 
 
TIMELINE 
State approximate 
Stage 1 – Data Collection – 10 months 
Stage 2 – Data Analysis – 1 month 


duration of time to 
completion of data 
collection as well as 
ultimate completion 
of project 
Stage 3 – Presentation/Publication – 1 month 
 
Projected Start Date – August 2015 
Projected End Date – June 2016 
DISCLOSURES OF 
FACULTY AND 
FUNDING 
KJOC 
TARGET JOURNAL 
Arthroscopy, AJSM, OJSM, JBJS 
TARGET MEETINGS 
AOSSM, AANA 
 

SAP_001.pdf: 
Protocol Title, "Pain Outcomes After Anterior Cruciate Ligament Reconstruction with Posterior Capsular 
Marcaine Injection” 
Cedars IRB # Pro41651 
NCT # 02826551 
Statistical Analysis Plan  
 
Based on previous studies, the Mann-Whitney U test will check differences between numeric variables. 
Nonparametric Kruskal-Wallis tests can compare the analgesia level in the two groups and if possible 
ANOVA test can compare the analgesia duration. Chi-square tests will be utilized for any potential 
complications which will also be recorded. (J Inj Violence Res. 2013 Jun; 5(2): 84-88.) (Acta Ortop Bras. 
2012;20(5); 285-90)   
Power Analysis   
Prelim Power Analysis per STATS department @ Cedars: sample sizes of 26 for each group (N1=N2=26) = 
Total 52 patients to achieve 80% power to reject the null hypothesis of equal means when the 
population mean difference is 2 with a standard deviation for both groups of 2.5 and with a significance 
level (alpha) of 0.050 using a two-sided two-sample equal-variance t-test. A total of 60 patients will be 
enrolled to ensure we achieve adequate power for the study.