Clinical trial NCT03094663
Conditions: Knee Arthropathy
Keywords: IPACK PAI
Sponsor: Hospital for Special Surgery, New York
Start date: 2017-02-28; Completion date: 2018-09-01
Enrollment: 86 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A comparison of two pain control methods - the combination of Adductor Canal Block (ACB)/Periarticular Injection (PAI)/Infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (IPACK) versus the Periarticular Injection (PAI) - in patients undergoing total knee arthroplasty. Primary outcome is NRS pain scores with ambulation on postoperative day one (24 hours post-block administration).

Detailed description:
Total knee arthroplasties (TKA) are severely painful surgeries that require optimal pain control to ensure expeditious recovery and discharge. Nerve blocks, such as the femoral and sciatic nerves, are instrumental in effectively providing pain relief and improving patient satisfaction. However, though pain scores notably decreased with the introduction of nerve blocks, motor blockade rendered these patients immobile and may pose a fall risk early in the post-operative period. The advent of ultrasound introduces newer block techniques with adequate analgesia without the cost of motor blockade.

The adductor canal block serves as an alternative to the femoral or sciatic nerve blocks in providing anterior knee analgesia without significantly compromising quadriceps strength. However, patients' posterior knee compartment remains an issue for pain control. Sciatic and posterior tibial nerve blocks were implemented but again, results in motor blockade. A small percentage of sciatic nerve block cases also exhibit foot drop due to peroneal nerve injury. Alternatively, as a sensory block, the periarticular injection (PAI) proves to hasten ambulation and recovery after TKA. The PAI blind injection into the posterior capsule seems to aid in pain control of the posterior compartment and reduces the total number physical therapy sessions.

Injection in the interspace between the Popliteal Artery and Capsule of the posterior Knee (IPACK) provides an alternative to the PAI blind technique for analgesia in the posterior compartment. The IPACK block is not a nerve block, but rather infiltrates the area between the popliteal artery and femur. This area is rich with sensory nerve fibers from the posterior capsule of the knee, which originates from the sciatic and posterior tibial nerve. In this prospective study, we will compare pain scores between the three groups: ACB/PAI/IPACK, ACB/IPACK and PAI only. We will determine whether there is a difference between groups in NRS pain score with ambulation 24 hours post block administration.

Arms: arm 1: Combined spinal epidural anesthetic with 1.5% Mepivacaine (60mg)

1. Injection prior to cementation

   1. bupivacaine 0.5% with epinephrine 30cc;
   2. methylprednisolone, 40 mg/ml, 1 ml
   3. cefazolin, 500 mg in 10 ml
   4. normal saline, 22cc
2. Superficial injection prior to closure.

   1. 20cc 0.25% bupivacaine
   2. 2 mg IV dexamethasone. arm 2: Combined spinal epidural anesthetic with 1.5% Mepivacaine (60mg)

1. Injection prior to cementation

   1. bupivacaine 0.25% with epinephrine 30cc;
   2. methylprednisolone, 40 mg/ml, 1 ml
   3. cefazolin, 500 mg in 10 ml
   4. normal saline, 22cc
2. Superficial injection prior to closure.

   a. 20cc 0.25% bupivacaine
3. Adductor canal block technique (supine position, post IV sedation)

   a. Mid-thigh injection of 15 cc of bupivacaine 0.25% with 2 mg of PF Dexamethasone
4. IPACK technique (supine position) a. 25 cc 0.25% bupivacaine
Interventions: intervention 1: Bupivacaine with epinephrine intervention 2: Methylprednisolone intervention 3: Cefazolin intervention 4: 8 MHz. Chiba needle intervention 5: Bupivacaine with Dexamethasone intervention 6: Bupivacaine 25cc intervention 7: Bupivacaine 20cc intervention 8: Dexamethasone
Intervention descriptions: intervention 1: bupivacaine 0.5% with epinephrine 30cc intervention 2: 40 mg/ml, 1 ml intervention 3: 500 mg in 10 ml intervention 4: 22G/ 4 inches intervention 5: 15 cc of bupivacaine 0.25% with 2 mg of PF Dexamethasone intervention 6: 25 cc 0.25% bupivacaine intervention 7: 20cc 0.25% bupivacaine intervention 8: 2 mg IV dexamethasone.

Protocol documents:
Prot_SAP_000.pdf: 
 
Page 1 of 12 
 
 
 
 
 
 
 
 
Analgesia after Total Knee Arthroplasty: Adductor 
Canal Block with Periarticular 
Injection and IPACK (ACB/PAI/IPACK) versus 
Periarticular Injection (PAI). A 
Double-Blinded Randomized Controlled Trial 
 
FUNDER: 
Department of Anesthesiology 
PROTOCOL NO.: 
2016-0168 
VERSION & DATE: 
1/24/2017 
This document contains the confidential information of the Hospital for Special Surgery.  It is provided to you and your company’s personnel for 
review.  Your acceptance of this document constitutes an agreement that you will not disclose the information contained herein to others without 
the prior written consent of the Hospital for Special Surgery.  No other use or reproduction is authorized by Hospital for Special Surgery, nor does 
the Hospital for Special Surgery assume any responsibility for unauthorized use of this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 2 of 12 
 
 
TABLE OF CONTENTS 
 
TABLE OF CONTENTS ............................................ 2 
PROTOCOL SYNOPSIS ........................................... 3 
1.0 
INTRODUCTION ............................................. 4 
2.0 
OBJECTIVE(S) OF CLINICAL STUDY .......... 6 
3.0 
STUDY HYPOTHESES .................................. 6 
4.0 
STUDY DESIGN ............................................. 7 
4.1 
Endpoints ....................................................................................................................... 7 
4.1.1 
Primary Endpoint ...................................................................................................... 7 
4.1.2 
Secondary Endpoints ................................................................................................ 7 
4.2 
Study Sites ..................................................................................................................... 7 
5.0 
STUDY POPULATION ................................... 7 
5.1 
Number of Subjects ........................................................................................................ 7 
5.2 
Inclusion Criteria............................................................................................................. 7 
5.1 
Exclusion Criteria ........................................................................................................... 8 
1.0 
PROCEDURES ............................................... 8 
1.1 
Pre-Operative Protocol ................................................................................................... 8 
1.2 
Intra-Operative Protocol ................................................................................................. 8 
1.3 
Post-Operative Protocol ................................................................................................. 9 
1.4 
Physical Therapy .......................................................................................................... 10 
1.5 
Data Collection ............................................................................................................. 10 
2.0 
STATISTICAL ANALYSIS ............................ 11 
3.0 
ADVERSE EVENT ASSESSMENT .............. 11 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 3 of 12 
 
 
 
 
PROTOCOL SYNOPSIS 
 
Protocol Title: 
Analgesia after Total Knee Arthroplasty: Adductor Canal Block 
with Periarticular Injection and IPACK (ACB/PAI/IPACK) versus 
Periarticular Injection (PAI). A Double-Blinded Randomized 
Controlled Trial. 
Protocol Number: 
2016-0168 
Protocol Date: 
 
Sponsor: 
Department of Anesthesiology 
Principal Investigator: 
David Kim, MD 
Objective: 
A comparison of two pain control methods - the combination of 
Adductor Canal Block (ACB)/Periarticular Injection 
(PAI)/Infiltration of the interspace between the popliteal artery 
and the capsule of the posterior knee (IPACK) versus the 
Periarticular Injection (PAI) - in patients undergoing total knee 
arthroplasty. Primary outcome is NRS pain scores with 
ambulation on postoperative day one (24 hours post-block 
administration). 
Study Design: 
Prospective Cohort Study 
Enrollment: 
86 
Subject Criteria: 
 
1. Patients with osteoarthritis scheduled for a primary total 
knee arthroplasty with a participating surgeon 
2. Age 18 to 80 years 
3. Planned use of regional anesthesia 
4. Ability to follow study protocol 
5. English speaking (secondary outcomes include 
questionnaires validated in English only) 
6. Patients of participating surgeons: Drs. Alexiades, Mayman, 
Ranawat, Su, and Westrich 
Data Collection: 
Sources: EPIC, Medical Records, Anesthesiologist, Surgeon’s 
office, and Patient Report 
Variables: Name, DOB, Race, Gender, Ethnicity, BMI, ASA, 
Length of stay, Anesthesia, Surgery, Tourniquet start/end time, 
intra-op medication, NRS (at rest and with movement), opioid 
consumption, ORSDS, painOUT, time to reach DC Physical 
therapy, Nerve Block success, patient satisfaction with pain 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 4 of 12 
 
control, Knee injury and osteoarthritis outcome score (KOOS) 
junior, blinding assessment, patient discharge plans 
Statistical Analysis: 
• 
Proposed analysis: Two-sample t-test 
• 
Alpha level: 0.05 
• 
Beta or power level: 80% 
 
1.0 INTRODUCTION 
Total knee arthroplasties (TKA) are severely painful surgeries that require optimal pain 
control to ensure expeditious recovery and discharge. Nerve blocks, such as the femoral 
and sciatic nerves, are instrumental in effectively providing pain relief and improving patient 
satisfaction1-2. However, though pain scores notably decreased with the introduction of 
nerve blocks, motor blockade rendered these patients immobile and may pose a fall risk 
early in the postoperative period3-6. The advent of ultrasound introduces newer block 
techniques with adequate analgesia without the cost of motor blockade. 
 
The adductor canal block serves as an alternative to the femoral nerve block in providing 
anterior knee analgesia without significantly compromising quadriceps strength7-10. However, 
patients’ posterior knee compartment remains an issue for pain control. Sciatic and posterior 
tibial nerve blocks were implemented but again, results in motor blockade. A small 
percentage of sciatic nerve block cases also exhibit foot drop due to peroneal nerve injury11. 
Alternatively, as a sensory block, the periarticular injection (PAI) proves to hasten 
ambulation and recovery after TKA12. The PAI blind injection into the posterior capsule 
seems to aid in pain control of the posterior compartment and reduces the total number of 
physical therapy sessions13. 
 
Injection in the interspace between the Popliteal Artery and Capsule of the 
posterior Knee (IPACK) provides an alternative to the PAI blind technique for 
analgesia in the posterior compartment14. The IPACK block is not a nerve block, 
but rather infiltrates the area between the popliteal artery and femur15. This area 
is rich with sensory nerve fibers from the posterior capsule of the knee, which 
originates from the sciatic and posterior tibial nerve16. In this prospective study, 
we will compare pain scores between two groups: ACB/PAI/IPACK and PAI only. 
We will determine whether there is a difference between groups in NRS pain 
score with ambulation 24 hours post block administration. 
 
References: 
 
1. Holm B, Kristensen MT, Bencke J, Husted H, Kehlet H, Bandholm T. Loss of 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 5 of 12 
 
knee-extension strength is related to knee swelling after total knee arthroplasty. 
Arch Phys Med Rehabil . 2010;91:1770–1776. 
 
2. Huebner, D, Benthien JP. Efficacy of continuous catheter analgesia of the 
sciatic nerve after total knee arthroplasty. Swiss Med Wkly. 2015;147:w14119. 
 
3. Ilfeld, BM, Duke, KB, Donohue, MC. The Association between Lower Extremity 
Continuous Peripheral Nerve Blocks and Patient Falls After Knee and Hip 
Arthroplasty. Anesth Analg. 2010: 111(6): 1552-1554. 
 
4. Mizner RL, Petterson SC, Stevens JE, Vandenborne K, Snyder-Mackler L. Early 
quadriceps strength loss after total knee arthroplasty. The contributions of 
muscle atrophy and failure of voluntary muscle activation. J Bone Joint Surg Am . 
2005;87: 1047–1053. 
 
5. Johnson RL, Kopp SL, Hebl JR, Erwin PJ, Mantilla CB. Falls and major 
orthopedic surgery with peripheral nerve blockade: a systematic review and 
meta-analysis. Br J Anaesth . 2013;110:518–528. 
 
6. Muraskin SI, Conrad B, Zheng N, Morey TE, Enneking FK. Falls associated with 
lower-extremity-nerve blocks: a pilot investigation of mechanisms. Reg Anesth 
Pain Med . 2007;32:67–72. 
 
7. Kim DH, Lin Y, Goytizolo EA, Kahn RL, Maalouf DB, Manohar A, Patt ML, Goon 
AK, Lee YY, Ma Y, Yadeau JT. Adductor canal block versus femoral nerve block 
for total knee arthroplasty: a prospective, randomized, controlled trial. 
Anesthesiology. 2014 Mar;120(3):540-50. 
 
8. Lund J, Jenstrup MT, Jaeger P, Sorensen AM, Dahl JB. Continuous adductorcanal- 
blockade for adjuvant post-operative analgesia after major knee surgery: 
preliminary results. Acta Anaesthesiol Scand . 2011;55:14–19. 
 
9. Jenstrup MT, Jaeger P, Lund J, et al. Effects of adductor-canal-blockade on 
pain and ambulation after total knee arthroplasty: a randomized study. Acta 
Anaesthesiol Scand . 2012;56:357–364. 
 
10.  YaDeau JT, Goytizolo EA, Padgett DE, Liu SS, Mayman DJ, Ranawat AS, et 
al. Analgesia after total knee replacement: local infiltration versus epidural 
combined with a femoral nerve blockade: A prospective, randomised pragmatic 
trial. Bone Joint J 2013; 95-B: 629–35. 
 
11. Schinsky, MF, Macaulay W, Parks, ML, Kiernan, H, Nercessian, OA. Nerve 
injury after primary total knee arthroplasty. J of Arthroplasty. 2001;16(8):1048- 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 6 of 12 
 
1054. 
 
12. Kovalak, E, Dogan, AT, Uzumcugil, O, Obut, A, Yildiz, AS, Kanay, E, Tuzuner, 
T, Ozyuvaci, E. A comparison of continuous femoral nerve block and periarticular 
local infiltration analgesia in the management of early period pain developing 
after total knee arthroplasty. Acta Orthrop Traumatol Turc. 2015;49(3):260-266. 
 
13. Horn, BJ, Cien, A, Reeves, P, Pathak, P, Taunt, CJ. Femoral Nerve Block vs. 
Periarticular bupivacaine Liposome injection after primary total knee arthroplasty: 
effect on patient outcomes. 2015. 115:714-719. 
 
14. Elliott CE, Myers TJ, Soberon JR, et al. The Adductor Canal Block Combined 
with iPACK Improves Physical Therapy Performance and Reduces Hospital 
Length of Stay (Abstract 197). Presented at the 40th Annual Regional 
Anesthesiology and Acute Pain Medicine Meeting (ASRA), May 14-16, 2015, in 
Las Vegas, Nevada. 
 
15. NYSORA - The New York School of Regional Anesthesia: NYSORA Webcast 
Series: Innovative Regional Techniques for Analgesia After Total Knee 
Arthroplasty 
 
16. Horner G., Dellon AL. Innervation of the human knee joint and implications for 
surgery. Clin Orthop Relat Res . 1994;301:221–226. 
2.0 OBJECTIVE(S) OF CLINICAL STUDY 
 
The purpose of this study is to compare two anesthesia methods in reducing pain with 
movement 24 hours after surgery - the Periarticular Injection (PAI) vs. a combination of 
the Adductor Canal Block (ACB), Periarticular Injection (PAI) and Infiltration of the 
interspace between the Popliteal Artery and Capsule of the posterior Knee (IPACK). 
Research questions/specific aims: 
a) Is there a difference in NRS pain scores with ambulation 24 hours post block 
administration between patients that receive ACB/PAI/IPACK vs. PAI? 
3.0 STUDY HYPOTHESES 
We hypothesize that there will be a difference in NRS pain score with ambulation 24 
hours post block administration between patients that receive ACB/PAI/IPACK vs. PAI. 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 7 of 12 
 
4.0 STUDY DESIGN 
4.1 
Endpoints 
4.1.1 
Primary Endpoint 
a) Our primary outcome will be NRS pain score with ambulation 24 hours post block 
administration. 
 
4.1.2 
Secondary Endpoints 
a) Opioid consumption at 24 hours on POD 1, 48 hours on POD 2 and 72 hours 
on POD 3 
b) NRS at rest at DOS (4 hours post-block), 24 hours on POD 1 and 48 hours on 
POD2 
c) NRS with movement on DOS and 48 hours on POD 2 
d) Physical Therapy milestones - time to reach discharge criteria 
e) Patient satisfaction with pain control 
f) PainOUT 
g) Hospital length of stay 
h) ORSDS 
i) Knee Injury and Osteoarthritis Outcome score (KOOS) Junior 
j) Patient discharge plans 
 
Secondary outcomes will be measured on the day of surgery upon spinal resolution (4 hours 
post induction), once at 24 hours on POD 1 and at 48 hours on POD 2 post-block 
administration. ORSDS, and pain Outcomes Questionnaire (painOUT) will be administered 
at the same intervals. The KOOS-Jr will be administered by Research team on pre 
operatively on DOS and at 6 weeks postop by surgeon's office. Length of hospital stay, and 
narcotic consumption will be obtained from EPIC. 
4.2 
Study Sites 
This study will take place at the main campus of the Hospital for Special Surgery (HSS). 
5.0 STUDY POPULATION 
5.1 
Number of Subjects 
86 
5.2 
Inclusion Criteria 
Subjects of either gender will be included if: 
• 
Patients with osteoarthritis scheduled for a primary total knee arthroplasty with a 
participating surgeon 
• 
Age 18 to 80 years 
• 
Planned use of regional anesthesia 
• 
Ability to follow study protocol 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 8 of 12 
 
• 
English speaking (secondary outcomes include questionnaires validated in English 
only) 
• 
Patients of participating surgeons: Drs. Alexiades, Mayman, Ranawat, Su, & 
Westrich 
5.1 
Exclusion Criteria 
Subjects will be excluded from the study if: 
• 
Younger than 18 years old and older than 80 
• 
Patients undergoing general anesthesia 
• 
Allergy or intolerance to one of the study medications 
• 
BMI > 40 
• 
Hepatic or renal insufficiency 
• 
Diabetes 
• 
ASA of IV 
• 
Chronic gabapentin/pregabalin use (regular use for longer than 3 months) 
• 
Chronic opioid use (taking opioids for longer than 3 months, or daily oral morphine 
equivalent of >5mg/day for one month) 
• 
Patients with severe valgus deformity and flexion contracture 
• 
Patients with preexisting mild dementia or cognitive decline 
1.0 PROCEDURES 
1.1 
Pre-Operative Protocol 
Both groups will receive preoperative meloxicam (7.5mg PO if age 75 or older; 15 
mg otherwise) + extended release oxycontin (10mg PO). 
 
Patients will be randomized into one of the two following groups: ACB/PAI/PACK or 
PAI. The randomization schedule will be created using SAS software by a member of 
the Healthcare Research Institute not otherwise involved in the trial. 
1.2 
Intra-Operative Protocol 
Both groups will receive intraoperative intravenous sedation with midazolam and 
propofol. Patients will not be given intravenous ketamine during the operation. 
Patients will be given 4mg ondansetron (IV Push), 2mg famotidine (IV Push), and up 
to 100mcg fentanyl. 
A combined spinal epidural anesthetic with 1.5% Mepivacaine (60mg) will be 
performed for both groups. 
If the surgery is prolonged (>2 hours), the anesthesiologist will use an epidural bolus 
with 2% lidocaine (10cc) to maintain surgical anesthesia. The epidural will be 
removed prior to leaving the operating room. 
Group 1- Periarticular (PAI) only group 
The surgeon will perform the PAI; one deep injection prior to cementation and then a 
second more superficial injection prior to closure. The deep injection will consist of 
bupivacaine 0.5% with epinephrine, 30cc; methylprednisolone, 40 mg/ml, 1 ml; 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 9 of 12 
 
cefazolin, 500 mg in 10 ml; normal saline, 22cc. The superficial injection will be 20cc 
0.25% bupivacaine. Patients will also receive 2 mg IV dexamethasone. 
Group 2- ACB with IPACK and PAI group 
PAI administered as above. The local anesthetic used for the PAI technique will be 
altered to prevent local anesthetic systemic toxicity. 30 cc of 0.25% bupivacaine with 
epinephrine will be used for the deep injection and 20cc of 0.25% bupivacaine for the 
superficial injection. A previous study done by Dr. Goytizolo (ACB/PAI),used 
equivalent local anesthetic amount without any adverse events. 
Adductor canal block technique; supine position, after IV sedation. Ultrasound guided 
with c60 sonosite probe (5-2 Hz). Chiba needle, 22 G / 4 inches. Identify the femoral 
artery in the adductor canal deep to the Sartorius muscle. Mid-thigh injection of 15 cc 
of bupivacaine 0.25% with 2 mg of Preservative free Dexamethasone. The local 
anesthetic will be delivered periarterial with spread anterior to the femoral artery, 
encompassing 9 o’clock to 3 o’clock position of the artery. 
*The block function will be assessed and recorded by the Anesthesiologist 
postoperatively. The assessment of the adductor canal block will be done in the 
Recovery room after the resolution of the spinal anesthesia. We will use an alcohol 
swab to test the cold sensation first on the non-operated leg and then on the 
operated one. The test will be performed at the level of the medial malleoli of the 
tibia. If the patient has sensation or no sensation will be recorded as block working or 
NOT working, respectively. The same procedures will be followed for the periarticular 
injection only group, so as to not unblind participating patients. 
IPACK technique: prone or supine, frog-leg position. Ultrasound guided with linear 
transducer 10 MHz or curvilinear 8 MHz. 22G 4 inch Chiba needle. Identify the 
popliteal artery at popliteal crease; move cephalad, just beyond the femoral 
condyles. Identify space between the femur and popliteal artery. From medial to 
lateral, place needle in between the popliteal artery and femur with the tip ending 2-3 
cm lateral to the artery. Inject 25 cc of 0.25% bupivacaine infiltrating the area 
between the artery and femur. 
1.3 
Post-Operative Protocol 
Analgesia: 
Postoperative analgesia will consist of: 
• 
Acetaminophen (1 g IV q 6 hr x 3 doses; then 1g PO q 8hr) 
• 
Ketorolac (30 mg IV q 6 hr X 4 doses, 15 mg for 75 or older) 
• 
Dexamethasone (4mg IV push PRN) 
• 
Oxycodone (5 - 10 mg q 3 hr PRN) 
• 
Meloxicam daily (7.5mg PO if age 75 or older; 15 mg otherwise, to start after 
ketorolac is finished). 
• 
Ondansetron (4mg IV q 8 hr PRN nausea) 
• 
Metoclopramide (10mg IV q 6 hr PRN nausea) 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 10 of 12 
 
 
In cases of severe pain (NRS scores greater than 6 for >2 hours), salvage therapy 
will be available using intravenous hydromorphone PCA. 
1.4 
Physical Therapy 
Standard of Care - one session DOS, two sessions on POD1 and POD 2. 
1.5 
Data Collection 
The following data will be collected: 
 
Questionnaires administered by Research staff: 
1. DOS, pre-op – NRS pain scores, KOOS Jr 
2. DOS, upon spinal resolution - NRS pain scores, painOUT, ORSDS 
3. POD 1 – NRS pain scores, painOUT, ORSDS, 
4. POD 2 – NRS pain scores, painOUT, ORSDS, blinding assessment 
5. 6 weeks post-op – KOOS Jr (if not administered by surgeon's office) 
 
Pre-operative/Baseline 
• 
Name 
• 
DOB 
• 
Race 
• 
Gender 
• 
Ethnicity 
• 
BMI 
• 
ASA 
• 
NRS (at rest and with movement) 
• 
Knee Injury and Osteoarthritis Outcome Score (KOOS) Junior 
 
Surgical procedure (Intra-operative) 
• 
Anesthesia, Surgery, Tourniquet Start/End Time 
• 
Intra-op medication 
 
Day of Surgery 
• 
NRS (at rest and with movement) 
• 
Opioid consumption 
• 
OSRDS 
• 
painOUT 
• 
Time to reach DC Physical Therapy 
 
Post-Operative Day 1 (POD 1) 
• 
NRS (at rest and with movement) 
• 
Opioid consumption 
• 
OSRDS 
• 
painOUT 
• 
Time to reach DC Physical Therapy 
 
Post-Operative Day 2 (POD 2) 
• 
NRS (at rest and with movement) 


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 11 of 12 
 
• 
Opioid consumption 
• 
OSRDS 
• 
painOUT 
• 
Time to reach DC Physical Therapy 
• 
Patient satisfaction with pain control 
• 
Blinding assessment 
 
Post-Operative 6-weeks 
• 
Knee injury and osteoarthritis outcome 
 
2.0 STATISTICAL ANALYSIS 
• 
Proposed analysis: two-sample t-test 
• 
Interim analysis planned: No 
• 
Alpha level: 0.05 (one-sided) 
• 
Beta or power level: 80% 
• 
Primary outcome variable estimate: NRS pain score with ambulation 24 hours 
post block administration in PAI group: 4.9 (Sawhney 2016) ± 3.0 (rounded 
up from 2.7; Sawhney, 2016; YaDeau, 2013). 
• 
Number of groups being compared: 2 
• 
Effect size or change expected between groups: 2 points (Farrar, 2001) 
• 
Resulting number per group: 39 
• 
Total sample size required: 78 + additional 10% to account for attrition = 86 
 
References: 
 
1. Sawhney M, Mehdian H, Kashin B, Ip G, Bent M, Choy J, McPherson M, Bowry R. Pain 
after Unilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial 
Examining the Analgesic Effectiveness of a Combined Adductor canal peripheral nerve 
block with periarticular infiltration versus adductor canal nerve block alone versus 
periarticular infiltration alone. Reg Anes 2016; 122(6): 2040-2046. 
 
2. YaDeau JT, Goytizolo EA, Padgett DE, Liu SS, Mayman DJ, Ranawat AS, et al. 
Analgesia after total knee replacement: local infiltration versus epidural combined with a 
femoral nerve blockade: A prospective, randomised pragmatic trial. Bone Joint J 2013; 95-B: 
629–35. 
 
3. Farrar JT, Young JP, Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of 
changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 
2001;94(2):149–58. 
 
3.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report.  


 
Protocol Number: 2016-0168  
Version Date: 4/8/2022  
 
 
Page 12 of 12