Effect of Perioperative Opioid Education on Outcomes After Total Knee Arthroplasty: A Randomized Study
Phase: NA
Conditions: Arthropathy of Knee, Post Operative Pain, Opioid Use, Opioid Abuse, Opioid Misuse
Sponsor: Hospital for Special Surgery, New York

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Effect of Perioperative Opioid Education on 
Outcomes After Total Knee Arthroplasty: A 
Randomized Study 
 
FUNDER: 
Department of Anesthesiology 
PROTOCOL NO.: 
2022-1286 
VERSION & DATE: 
9/22/2022 
 
 
 
 
 
 
 
 
 
 
 
 
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 

 
Protocol Number: 2022-1286  
Version Date: 9/28/2022 
 
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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. 
 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................ 2 
PROTOCOL SYNOPSIS ........................................... 3 
1.0 
INTRODUCTION ............................................. 5 
2.0 
OBJECTIVE OF CLINICAL STUDY ............... 5 
3.0 
STUDY HYPOTHESES .................................. 5 
4.0 
STUDY DESIGN ............................................. 5 
4.1 
Study Duration ................................................................................................................ 5 
4.2 
Endpoints ....................................................................................................................... 6 
4.2.1 
Primary Endpoint ...................................................................................................... 6 
4.2.2 
Secondary Endpoints ................................................................................................ 6 
4.3 
Study Sites ..................................................................................................................... 6 
5.0 
STUDY POPULATION ................................... 6 
5.1 
Number of Subjects ........................................................................................................ 6 
5.2 
Inclusion Criteria............................................................................................................. 6 
5.3 
Exclusion Criteria ........................................................................................................... 6 
5.4 
Randomization ............................................................................................................... 7 
6.0 
PROCEDURES ............................................... 7 
6.1 
Surgical Procedure ......................................................................................................... 7 
6.2 
Medical Record Requirements ....................................................................................... 7 
6.3 
Data Collection ............................................................................................................... 7 
7.0 
STATISTICAL ANALYSIS .............................. 8 
8.0 
ADVERSE EVENT ASSESSMENT ................ 8 
9.0 
REFERENCES................................................ 8 
 
 
 

 
Protocol Number: 2022-1286  
Version Date: 9/28/2022 
 
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PROTOCOL SYNOPSIS 
Protocol Title: 
Effect of Perioperative Opioid Education on Outcomes After total knee 
arthroplasty: A Randomized Study 
Protocol Number: 
2022-1286 
Protocol Date: 
9/22/2022 
Sponsor: 
Department of Anesthesiology 
Principal 
Investigator: 
Bradley H. Lee, MD 
Products: 
N/A 
Objective: 
The aim of this study is to explore how a comprehensive educational 
pathway focusing on aspects of pain control and proper opioid use with 
repeated sessions will affect outcomes after total knee arthroplasty by 
comparing three groups – patients who 1) attend the virtual webinar, 2) 
an in-person session with PDF, and 3) a video session with PDF. 
Study Design: 
Randomized Study 
Enrollment: 
36 
Subject Criteria: 
Inclusion: 
• 
Age between age 18 and 80 years old 
• 
Undergoing primary total knee replacement surgery  
• 
English speaking 
 
Exclusion: 
• 
History of chronic opioid use (continuous opioid use for 3 or more 
months) 
• 
Opioid use within the past 3 months 
• 
Contraindication to NSAIDs or acetaminophen 
• 
Contraindication or allergy to opioids 
• 
Discharge to rehab or skilled nursing facility (opioids are not 
prescribed by HSS providers) 
• 
Contraindication or refusal to receive neuraxial anesthesia or 
peripheral nerve blocks (PNB) 
• 
Revision surgery 
• 
Ambulatory surgery 
• 
Patient is pregnant 
Study Duration: 
1 year 
Data Collection: 
Sources: EPIC, Medical Records, and Patient Reported. 
 
Variables: Name, MRN, DOB, Race, Ethnicity, Gender, Height, 
Weight, BMI, ASA class, email address, phone number, level of 
education, co-morbidities (diabetes, high blood pressure, cholesterol, 
rheumatological conditions, allergies), alcohol and tobacco use, Patient 
education class completion, Surgery details (surgeon, laterality, 
duration, tourniquet use), Anesthesia details (neuraxial, PNB, 
medications given), hospital length of stay (LOS), QoR15, Average 

 
Protocol Number: 2022-1286  
Version Date: 9/28/2022 
 
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NRS Pain Score, Opioid consumption (assess for cessation of opioids 
due to adverse effects), use of multimodal analgesia, opioid refill 
requests, opioid storage, opioid disposal, video on opioid and pain 
management viewed during hospitalization, reported sources of 
information on opioids and pain management, intervention 
assessment/feedback 
Statistical Analysis: 
1. Proposed analysis (e.g., student’s t-test, ANOVA, chi-
square, regression, etc.): Three Two-Sample T-tests: Video 
+ PDF vs. Control and In-Person + PDF vs. Control , Video + 
PDF vs In-Person + PDF 
2. Interim analysis planned?: No 
3. Alpha level:  NA (Pilot Study) 
4. Beta or power level:  NA (Pilot Study) 
5. Primary outcome variable estimate (mean +/- s.d. for 
continuous outcome, frequency/percentage for 
categorical variable): NA (Pilot Study) 
6. Number of groups being compared (use 1 for paired 
analysis within the same subjects):  3 (2 Treatments vs. 1 
Control) 
7. Effect size or change expected between groups:  NA (Pilot 
Study) 
8. Resulting number per group: 12 
9. Total sample size required: 12 x 3 = 36 patients  
 
 
 
 

 
Protocol Number: 2022-1286  
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1.0 INTRODUCTION 
Pain control after knee arthroplasty is challenging even with regional anesthesia, and patients 
often use opioids for prolonged periods and are at risk for developing chronic opioid use (Grosu, 
Hsia). Prior qualitative assessment revealed potential inconsistencies in pain expectations and 
the role of opioids (Lee). Specifically, patients acknowledge that opioids should be used to 
control pain enough to allow recovery, yet most feel that the goal with opioids is to experience 
minimal or virtually no pain (Lee). Therefore, patients may benefit from setting appropriate 
expectations of postoperative pain (Horn). Educational interventions have led to lower pain 
scores and may lead to earlier opioid cessation (Syed, Stepan, Egan, Nahhas). In addition, 
multimodal analgesia is an effective strategy for postoperative analgesia (Memtsoudis) and 
emphasizing the importance will hopefully improve compliance given less than half of patients 
seem to appreciate the purpose of multimodal analgesia (Lee). 
Apart from pain control, patients should also understand details about opioid risks, storage, and 
disposal in order to promote proper handling (Syed, Lee). Prior studies show improved rates of 
handling and disposal with education (Nahhas). While prior studies of educational interventions 
have shown benefits, they often look at limited aspects of opioid use, such as opioid 
consumption (Syed, Nahhas). The aim of this study is to explore how a comprehensive 
educational pathway focusing on aspects of pain control and proper opioid use will affect 
outcomes after total knee arthroplasty that include pain, opioid refills, storage, and disposal. 
2.0 OBJECTIVE OF CLINICAL STUDY 
 
The current education process at HSS involves patient referral to a virtual webinar which is 
optional. Pain topics are covered within a broader 50-minute presentation on numerous topics 
related to surgery. Information on pain topics may be difficult to process and retain because it is a 
single exposure that is combined with multiple unrelated topics, and there is no repetition or 
reference provided. The aim of this study is to explore how a comprehensive educational pathway 
focusing on aspects of pain control and proper opioid use with repeated sessions will affect 
outcomes after total knee arthroplasty by comparing three groups – patients who attend the virtual 
webinar, an in-person session with PDF, and a video session with PDF. 
3.0 STUDY HYPOTHESES 
Educational intervention delivered in repeated sessions either in-person or via video during 
perioperative period (prior to surgery then POD1) will reduce opioid refill requests within 30 days 
compared with opioid education delivered through webinar. Initial prescription is for 42 tabs of 
oxycodone 5 mg q4h prn pain, though alternate opioids may be used. 
4.0 STUDY DESIGN 
 
4.1 
Study Duration 
September 2022-September 2023 

 
Protocol Number: 2022-1286  
Version Date: 9/28/2022 
 
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4.2 
Endpoints 
4.2.1 
Primary Endpoint 
• 
Opioid refill requests 
4.2.2 
Secondary Endpoints 
• 
Hospital LOS 
• 
QoR15 at baseline, POD1, POD7, POD14 
• 
NRS Pain Score at POD0, POD1, POD7, POD14 
• 
Opioid consumption (in Oral Morphine Equivalents) at POD0, POD1, POD7, POD14 
• 
Rates of compliance with multimodal regimen 
• 
Patients in this study will be prescribed acetaminophen, NSAIDs, and opioid (oxycodone, 
tramadol, etc.). Patients will keep “pain diary” to record use of each medication. 
Compliance will be defined as the percentage of prescribed medication (acetaminophen 
or NSAID) that is actually taken. 
• 
Rates of proper opioid storage (opioids are reportedly stored “locked and hidden”) 
• 
Rates of proper opioid disposal (opioids are reportedly disposed of by one of the 
accepted proper disposal methods) 
4.3 
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 
36 
5.2 
Inclusion Criteria 
Subjects of either gender will be included if they: 
• 
Age between age 18 and 80 years old 
• 
Undergoing primary total knee replacement surgery  
• 
English speaking 
 
5.3 
Exclusion Criteria 
Subjects will be excluded from the study if they: 
• 
History of chronic opioid use (continuous opioid use for 3 or more months) 
• 
Opioid use within the past 3 months 
• 
Contraindication to NSAIDs or acetaminophen 
• 
Contraindication or allergy to opioids 
• 
Discharge to rehab or skilled nursing facility (opioids are not prescribed by HSS 
providers) 
• 
Contraindication or refusal to receive neuraxial anesthesia or peripheral nerve blocks 
(PNB) 
• 
Revision surgery 
• 
Ambulatory surgery 
• 
Patient is pregnant 

 
Protocol Number: 2022-1286  
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5.4 
Randomization 
Participants will be assigned at random to one of 3 study groups: 
o 
Group 1 (control): Patients should have been referred to and attended the Hospital's 
standard 1-hour virtual patient education webinar prior to surgery. 
o 
Group 2 (in-person): Patients will receive two in-person education sessions (1st 
session before surgery and 2nd session after surgery). Patients will also receive pdf 
handouts about opioids and pain management. 
o 
Group 3 (video): Patients will receive two video education sessions (1st session 
before surgery and 2nd session after surgery). Patients will also receive pdf handouts 
about opioids and pain management. 
6.0 PROCEDURES 
6.1 
Surgical Procedure 
Total knee arthroplasty (TKA) 
6.2 
 Medical Record Requirements 
 
Using EPIC, research staff will review the patient's medical history to determine eligibility to 
participate in the study. 
 
PHI that will be reviewed: 
 
Name, DOB, preferred language, medical history, allergies, current outpatient medication, 
weight & body mass index 
 
6.3 
Data Collection 
 
The following data will be collected: 
 
Pre-operative/Baseline 
Name, MRN, DOB, Race, Ethnicity, Gender, Height, Weight, BMI, ASA class, email address, 
phone number, level of education, co-morbidities, alcohol and tobacco use, patient education 
class completion,  
 
Surgical procedure 
• 
Surgery details (date of surgery, surgeon, laterality, duration, tourniquet use) 
• 
Anesthesia details (neuraxial, PNB, medications given) 
 
Follow-up visits (Post-operative day of surgery (POD) 1, 7, 14, 21, 30, 60,) 
• 
QoR15 
• 
Average NRS Pain Score 
• 
Opioid consumption 
• 
Use of multimodal analgesia 
• 
Opioid refill requests 
• 
Opioid storage 
• 
Opioid disposal 
• 
Video on opioid storage/disposal viewed during hospitalization? 

 
Protocol Number: 2022-1286  
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• 
Video on pain management viewed during hospitalization? 
• 
Reported sources of information on opioids and pain management 
• 
Intervention assessment/feedback 
7.0 STATISTICAL ANALYSIS 
Proposed analysis (e.g., student’s t-test, ANOVA, chi-square, regression, etc.): Three Two-
Sample T-tests: Video + PDF vs. Control and In-Person + PDF vs. Control , Video + PDF vs In-
Person + PDF 
Interim analysis planned?: No 
Alpha level:  NA (Pilot Study) 
Beta or power level:  NA (Pilot Study) 
Primary outcome variable estimate (mean +/- s.d. for continuous outcome, 
frequency/percentage for categorical variable): NA (Pilot Study) 
Number of groups being compared (use 1 for paired analysis within the same subjects):  3 
(2 Treatments vs. 1 Control) 
Effect size or change expected between groups:  NA (Pilot Study) 
Resulting number per group: 12 
Total sample size required: 12 x 3 = 36 patients  
 
8.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report. 
 
9.0 REFERENCES 
1. Lee BH, Wu CL. Educating patients regarding pain management and safe opioid use after 
surgery: a narrative review. Anesth Analg. 2020 Mar; 130(3):574-581. 
(https://pubmed.ncbi.nlm.nih.gov/31567320) 
2. Syed UAM, Aleem AW, Wowkanech C, et al. Neer Award 2018: the effect of preoperative 
education on opioid consumption in patients undergoing arthroscopic rotator cuff repair: a 
prospective, randomized clinical trial. J Shoulder Elb Surg. 2018;27(6):962-967. 
doi:10.1016/j.jse.2018.02.039 
3. Egan KG, De Souza M, Muenks E, Nazir N, Korentager R. Opioid consumption following 
breast surgery decreases with a brief educational intervention: a randomized, controlled trial. 
Ann Surg Oncol. 2020 Sep;27(9):3156-3162. doi: 10.1245/s10434-020-08432-7. Epub 2020 
Apr 13.PMID: 32285282 
4. Stepan JG, Sacks HA, Verret CI, Wessel LE, Kumar K, Fufa DT. Standardized perioperative 
patient education decreases opioid use after hand surgery: a randomized controlled trial. 
Plast Reconstr Surg. 2021 Feb 1;147(2):409-418. doi: 
10.1097/PRS.0000000000007574.PMID: 33235041 
5. Nahhas C, Hannon C, Yang J, Gerlinger T, Nam D, Della Valle C. Education increases 
disposal of unused opioids after total joint arthroplasty: a cluster-randomized controlled trial.  
J Bone Joint Surg Am. 2020 Jun 3;102(11):953-960. doi: 10.2106/JBJS.19.01166. 
6. Memtsoudis S, Poeran J, Zubizarreta N, Cozowicz C, Morwald E, et al. Association of 
multimodal pain management strategies with perioperative outcomes and resource utilization: 
a population-based study. Anesthesiology. 2018 May;128(5):891-902. 

 
Protocol Number: 2022-1286  
Version Date: 9/28/2022 
 
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7. Horn A, Kaneshiro, K, Tsui B. Preemptive and preventive pain psychoeducation and its 
potential application as a multimodal perioperative pain control option: a systematic review. 
Anesth Analg 2020 Mar;130(3):559-573. 
8. Grosu I, Lavand’homme P, Thienpont E. Pain after knee arthroplasty: an unresolved issue. 
Knee Surg Sports Traumatol Arthrosc. 2014 Aug;22(8):1744-58. 
9. Lee BH, Gbaje E, Goydos R, Wu C, Sideris A. Evaluating patient perceptions of pain 
management and opioid use prior to hip arthroplasty. Abstract presented at 46th Annual 
American Society of Regional Anesthesia and Pain Medicine; May 13-15, 2021 ; Lake Buena 
Vista, FL.  
10. Hsia HL, Takemoto S, van de Ven T, Pyati S, Buchheit T, et al. Acute pain is associated with 
chronic opioid use after total knee arthroplasty. Reg Anesth Pain Med. 2018 Oct;43(7):705-
711. 
11. Syed UAM, Aleem AW, Wowkanech C, et al. Neer Award 2018: the effect of preoperative 
education on opioid consumption in patients undergoing arthroscopic rotator cuff repair: a 
prospective, randomized clinical trial. J Shoulder Elb Surg. 2018;27(6):962-967. 
doi:10.1016/j.jse.2018.02.039 
12. Egan KG, De Souza M, Muenks E, Nazir N, Korentager R. Opioid consumption following 
breast surgery decreases with a brief educational intervention: a randomized, controlled trial. 
Ann Surg Oncol. 2020 Sep;27(9):3156-3162. doi: 10.1245/s10434-020-08432-7. Epub 2020 
Apr 13. PMID: 32285282 
13. Stepan JG, Sacks HA, Verret CI, Wessel LE, Kumar K, Fufa DT. Standardized perioperative 
patient education decreases opioid use after hand surgery: a randomized controlled trial. 
Plast Reconstr Surg. 2021 Feb 1;147(2):409-418. doi: 
10.1097/PRS.0000000000007574.PMID: 33235041 
14. Nahhas C, Hannon C, Yang J, Gerlinger T, Nam D, Della Valle C. Education increases 
disposal of unused opioids after total joint arthroplasty: a cluster-randomized controlled trial.  
J Bone Joint Surg Am. 2020 Jun 3;102(11):953-960. doi: 10.2106/JBJS.19.01166. 
15. Memtsoudis S, Poeran J, Zubizarreta N, Cozowicz C, Morwald E, et al. Association of 
multimodal pain management strategies with perioperative outcomes and resource utilization: 
a population-based study. Anesthesiology. 2018 May;128(5):891-902. 
16. Horn A, Kaneshiro, K, Tsui B. Preemptive and preventive pain psychoeducation and its 
potential application as a multimodal perioperative pain control option: a systematic review. 
Anesth Analg 2020 Mar;130(3):559-573. 
17. Lee BH, Wu CL. Educating patients regarding pain management and safe opioid use after 
surgery: a narrative review. Anesth Analg. 2020 Mar; 130(3):574-581. 
(https://pubmed.ncbi.nlm.nih.gov/31567320)