Clinical trial NCT04919317
Conditions: Pain, Postoperative Mammaplasty
Sponsor: Temple University
Start date: 2017-09-29; Completion date: 2020-11-25
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The addition of dexamethasone to non-liposomal bupivacaine in perineural blocks has been shown to enhance pain control and prolong the time until first request for postoperative narcotics in the fields of orthopedic, thoracic, and gynecologic surgery. This has not been investigated in any types of breast surgery. The investigators assessed if the combination of dexamethasone to bupivacaine in the preoperative field block prior to bilateral breast reduction surgery resulted in improved pain control relative to bupivacaine alone.

Detailed description:
The investigators conducted a double-blind randomized controlled trial to determine whether the addition of dexamethasone to bupivacaine in a preoperative Pecs II block resulted in improved pain control, relative to bupivacaine alone, in patients undergoing bilateral reduction mammaplasty.

Using a preassigned randomization list, patients were randomized to experimental and control groups in a ratio of 1:1 upon enrollment. Both groups received PECS II bupivacaine field blocks in the preoperative holding area, performed by an acute pain fellowship-trained anesthesiologist. The experimental group received 29mL of 0.5% bupivacaine mixed with 1mL 4mg/mL dexamethasone per side. The control group received 29mL 0.5% bupivacaine mixed with 1mL 0.9 saline solution per side. To maintain the blinded aspect of the study, the anesthesiologists were given pre-mixed vials labelled uniformly for the trial, regardless of the patient's treatment arm.

The patients all underwent bilateral breast reduction with a single surgeon. Postoperative pain regimens were standardized. Subjective pain scores, narcotic consumption, 4-hour interval vital signs, anti-emetic usage, and postoperative quality of life via an sf-36 questionnaire were all recorded per patient.

Arms: arm 1: Control group patients received 29mL bupivacaine plus 1mL 0.9% saline. Like the experimental group, 20mL of the mixture was injected into the fascial plane between the pectoralis minor and the serratus anterior muscles at the level of the third rib, while the remaining 10mL of the mixture was then injected into the fascial plane between the pectoralis major and pectoralis minor muscles during the same needlestick. arm 2: Experimental group patients received 29mL bupivacaine plus 1mL of 4mg/mL dexamethasone. Like the control group, 20mL of the mixture was injected into the fascial plane between the pectoralis minor and the serratus anterior muscles at the level of the third rib, while the remaining 10mL of the mixture was then injected into the fascial plane between the pectoralis major and pectoralis minor muscles during the same needlestick.
Interventions: intervention 1: Dexamethasone 4mg intervention 2: Saline
Intervention descriptions: intervention 1: The experimental group received 4mg dexamethasone added to their bupivacaine block preoperatively just prior to bilateral reduction mammaplasty. intervention 2: The control group received 1mL of 0.9% saline added to their bupivacaine block preoperatively just prior to bilateral reduction mammaplasty.

Protocol documents:
Prot_SAP_000.pdf: 
Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 1 of 11 
     Revision: June 16, 2017 
1) Abstract of the study 
Background: Patients undergoing reduction mammoplasty frequently suffer 
significant post procedure pain at the operative site.  While regional nerve 
block is routinely performed with bupivacaine, the effects of this are limited to 
the up to 8 hours of action provided by this drug.  Previous studies in 
orthopedic and thoracic surgery patients have demonstrated that addition of 
dexamethasone to the perineural block prolongs the duration of analgesia.  
This has never been studied in the plastic surgery patient.  We propose that 
addition of dexamethasone to the infiltration solution will prolong the duration 
of analgesia provided by a regional block and reduce the need for adjunct 
narcotic medication in the postoperative period following reduction 
mammaplasty.   
Methods: Patients undergoing elective Breast Surgery at Temple University 
Hospital will be randomized to receive a control standard perineural block with 
19-mL 0.5% bupivacaine +1mL 0.9% sterile saline or block with the 
experimental mixture of 19mL 0.5% bupivacaine + 1mL 4mg/mL 
dexamethasone solution for each breast.    Primary end points will be mean 
pain VAS score as measured every 4 hours postoperatively and 
postoperative narcotic consumption data during the admission following the 
procedure.  Secondary endpoints also observed will be anti-emetic 
consumption, vital signs, quality of life as assessed by SF-36 and Breast-Q 
questionnaires, and length of hospital stay.   
 
2) Protocol Title 
Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
3) IRB Review History 
No previous submissions 
4) Investigator 
Andrew Gassman, MD, Gaurav Trehan MD,  
5) Objectives 
This study aims to evaluate the effect of the addition of dexamethasone to a 
standard bupivacaine nerve block following reduction mammaplasty.  We 
propose that addition of dexamethasone to the infiltration solution will prolong 
the duration of analgesia provided by a regional block and reduce the need 
for adjunct narcotic medication in the postoperative period following reduction 
mammaplasty.   
 
6) Background 
 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 2 of 11 
     Revision: June 16, 2017 
Breast reduction is among the most common procedures performed by the 
Plastic Surgery division at Temple University Hospital.  These patients are 
generally admitted for 23 hour observation primarily due to significant 
postoperative pain.  Currently regional nerve block is routinely performed with 
bupivacaine infiltration.  This provides effective immediate postoperative pain 
control but is limited by the 2 to 8 hour duration of action provided by this 
drug.  These patients typically require significant amount of narcotic analgesia 
in the postoperative period.  Exparel® (bupivacaine liposome injection) is a 
commercially available long acting formulation of bupivacaine however its 
significant cost has been deemed prohibitively high for use at this and most 
other institutions. 
 
A number of studies in the anesthesia literature have demonstrated that addition 
of dexamethasone to bupivacaine when administered as a perineural block 
extends the duration of analgesia.  In Bjorn, et al. (Reg Anesth Pain Med, 2016 
Dec) saphenous nerve block with 10mL 0.5% bupivacaine + 1mL 0.4% 
dexamethasone after ankle surgery significantly extended the time to first 
narcotic request compared to control with bupivacaine alone.  Maher, et al. (Pain 
Med, 2016 Jul) examine the use of both IV dexamethasone (8mg) and 
combination perineural dexamethasone and bupivacaine as intercostal nerve 
block during VATS.  They demonstrate statistically significant decrease in pain at 
8, 20, and 24 hours postoperatively.  Other studies have obtained similar results 
in a variety of orthopedic and neurosurgical procedures. 
 
A PubMed search using terms “dexamethasone” and “nerve block” did not return 
any studies that pertain to plastic reconstructive surgeries including but not 
limited to breast reduction.  Additionally, searches using “breast reduction” and 
“nerve block” or “mammaplasty” and “nerve block” returned only 1 relevant study 
that examines the use of Exparel® nerve block during mastectomy (Abdelsattar 
2016).  Again, no studies examine methods of prolonging the duration of regional 
anesthesia after reduction mammaplasty 
 
 
7) Setting of the Human Research 
 
This study will be performed exclusively at Temple University Hospital.  
Patients will initially be identified and recruited during the preoperative clinic 
visit.  The study will again be described to the subjects and consent obtained 
in the preoperative holding area prior to the procedure.   
 
8) Resources Available to Conduct the Human Research 
 
The Plastic Surgery division at Temple University Hospital performs 
an average of 10 breast reduction mammaplasty procedures per 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 3 of 11 
     Revision: June 16, 2017 
month.  We anticipate that the vast majority of these patients will be 
eligible for study enrollment and will agree to participate in the 
study due to the potential for improved pain control  
 
Data collection is expected to occur over a period of 12 months.  
Much of this will be collected automatically from Epic patient data.  
With the assistance of the medical informatics department, an 
automated data collection framework is being developed. 
This study will be led by Dr. Andrew Gassman of the Plastic and 
Reconstructive Surgery Division and Dr. Gaurav Trehan from the 
Department of Anesthesia.  Dr. Gassman is an experienced 
researcher with multiple publications in the field of plastic surgery.  
He has a specific research interest in pain control.  Dr. Trehan is a 
specialist in pain medicine.  He completed a fellowship in pain 
medicine at the University of Pennsylvania.  He has book chapters 
and publications in the field of pain medicine. 
Research Support will be provided by plastic surgery and general 
surgery residents. Total project staff is expected to total at least 5 
people.  We expect this to be more than adequate to conduct this 
research 
Enrolled subjects will be admitted patients at Temple University 
Hospital.  They will have access to all of the medical and 
psychosocial services provided to patients of the hospital in the 
event of an adverse outcome as a result of participation in this 
study 
All persons involved in conducting this study will be fully briefed on 
the background and protocol by the primary investigator or study 
coordinator prior to any involvement with the study.  There will be 
ongoing oversight by the PI and study coordinator of all study 
subjects and personnel. 
 
9) Prior Approvals 
No prior approvals are required.  The Division of Plastic and 
Reconstructive Surgery and the Department of Anesthesia have 
approved this study. 
 
10) 
Study Design 
a) Recruitment Methods 
Research subjects will be identified in the plastic surgery clinic 
when they are scheduled for breast reduction surgery.  The study 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 4 of 11 
     Revision: June 16, 2017 
will be described to patients when they agree to surgery.  They will 
again be briefed on the study on the day of surgery.  No additional 
recruitment methods will be required.  No compensation will be 
provided to study participants. 
b) Inclusion and Exclusion Criteria 
Initial in office screening will easily identify all patients who are 
requesting and scheduling breast reduction surgery.  Criteria to be 
included in the study are women aged 18-80 undergoing elective 
bilateral breast surgery with ASA class 1-3.   
Exclusion criteria are allergy to any of the study medications, 
history of chronic pain condition or narcotic dependency, history of 
chronic renal or hepatic disease, history of diabetes mellitus, and 
history of previous post operative nausea and vomiting.  Prisoners 
and pregnant patients will also be excluded.  Screening for 
appropriate subjects will occur in the clinic.  ASA determination will 
be made by the anesthesia department during preoperative testing. 
  
c) Local Number of Subjects 
An average of 10 breast reductions are performed monthly at 
Temple University Hospital.  We expect nearly all of these patients 
to meet screening criteria and to agree to participate in this study 
 
d) Study-Wide Number of Subjects 
This is a single site study.  Anticipated number of subjects is 
approximately 60 
e) Study Timelines 
• Data collection will occur over a period of 12 months 
• Interim analysis will be conducted by an independent at 6 
months to confirm the quality of the data 
• Patient participation is limited to the length of the hospitalization 
for breast reduction procedure plus the first postoperative visit.  
For most subjects this will be 24 hours as inpatients with the 
postoperative visit occurring 1 week after surgery.   
f) Study Endpoints 
Primary study endpoints are average VAS pain score during 
hospitalization and postoperative narcotic usage during the 
hospitalization.  Secondary endpoints are need for antiemetic 
therapy, length of hospitalization, and aggregate pain and quality of 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 5 of 11 
     Revision: June 16, 2017 
life survey scores at the first post-operative visit.  .  Patient 
participation is concluded following the first post-operative visit  
Patient participation will be terminated if any adverse reaction to the 
study medication is noted. 
g) Procedures Involved in the Human Research 
Study subjects will undergo breast surgery by the individual surgeon’s 
standard technique.  No changes in surgical technique will occur as part of 
this study.  Regional nerve block with bupivacaine and/or lidocaine is 
typically offered to patients as part of this procedure and is considered 
standard of care. However, not all patients opt to receive a nerve block 
For the study, subjects will be randomized to experimental and control 
groups in a ratio of 1:1.  Randomization will occur upon enrollment in the 
study.  When the patient is enrolled, the investigator will use the Sealed 
Envelope™ simple randomization tool to assign the subject a treatment 
group.  Randomization occurs in random permuted blocks to achieve an 
even distribution between groups.  Patients will be blinded to their study 
group. 
All subjects will receive perineural nerve block in the preoperative holding 
area prior to the case performed by faculty from the anesthesia pain 
service.  An ultrasound guided pecs block will be performed.  For the 
block, the fascial plane separating the pectoralis major and pectoralis 
minor muscles is identified by ultrasound at the level of the 3rd rib.  A 
needle is advanced into this space and the local anesthetic is infiltrated. 
The experimental group will receive 29cc 0.5% bupivacaine mixed with 
1mL 4mg/mL dexamethasone for each side (40 cc total).  The control 
group will receive 29cc 0.5% bupivacaine mixed with 1mL 0.9% saline 
solution for each side.   
All patients will undergo standard breast reduction with no change in the 
standard operative technique. 
All patients will receive a standard postoperative pain regimen as follows: 
• Percocet 5/325 1 tab q4hr prn pain (moderate, 4 – 7) 
• Percocet 5/325 2 tabs q4hr prn pain (severe, 8 – 10) 
• IV 1mg Morphine q1hr prn breakthrough pain  
• IV 4mg Zofran q8hrs prn N/V 
This may be adjusted for patient drug allergies 
 
Bupivacaine is a local analgesic used routinely during surgical procedures.  
It is FDA approved for this indication.   
Dexamethasone is a glucocorticoid available in oral and intravenous 
formulations.  It is FDA approved for a multitude of anti-inflammatory 
indications. While off label, it is standard of care to provide IV 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 6 of 11 
     Revision: June 16, 2017 
dexamethasone to prevent post-operative nausea and vomiting.  It has not 
been evaluated by the FDA as an adjunct to local anesthesia.   
Pain VAS scores are routinely collected by nursing staff and entered into 
Epic. We will request pain evaluations at 4 hour intervals for study patients 
following surgery which will be entered into the Epic medical record.  
Medication administration is also captured in the electronic medical 
record.  Study data will be gathered from the Epic electronic medical 
record.   
Patients will be asked to complete the MD Anderson Brief Pain Inventory 
Short Form and both the Breast-Q or the SF-36 questionnaire at their first 
post-operative visit.   
As previously stated, regional block with bupivacaine alone is routinely 
offered and provided to patients.  Patients who do not consent to 
participate in the study will be offered a regional nerve block containing 
only bupivacaine.  Anesthesia pain service faculty will perform the block 
regardless of study participation or study group.   
 
h) Data and Specimen Banking 
Data will be collected and stored in an electronic database stored on the 
encrypted hospital network.  All data will be stored in a password 
protected and encrypted manner.   
 
Identifying patient information including name, date of birth, and medical 
record number and the associated study ID will be stored in a password 
protected document accessible only to the PI and study coordinator. 
 
A separate database containing the de-identified study ID number and all 
collected study data will also be stored in a password protected, encrypted 
file.  This file will contain clinical information such as pain scores, narcotic 
use, and length of stay.  This database will be accessible to all study 
personnel involved in administering the study. 
 
The database containing identifying patient information will be destroyed 
upon completion of all data analyses.  All patient medical records will be 
cleared of the study ID at this time.  The deidentified database will be 
maintained indefinitely for potential ongoing analysis.   
 
i) Data Management 
 
Prior to data collection, patients will be randomized into 2 groups (control or 
experimental). An independent source will generate a master list of study 
IDs and associated randomization status.  Patients will assigned within the 
master list and randomized accordingly per the master list. 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 7 of 11 
     Revision: June 16, 2017 
 
Data will be extracted from the Epic electronic medical record. Consultation 
with medical informatics has been obtained to assist with development of 
an automated data collection mechanism. Data will be stored in a 
spreadsheet that allows for manipulation and analysis. Patient surveys will 
be conducted a week after the procedure and documented on paper and 
the responses will be manually inputted into an electronic database 
(REDCap). Survey responses (REDCap) will be matched to inpatient data 
measurements (Epic) through study ID numbers. The spreadsheet itself 
will be encrypted and will be stored exclusively on hospital network 
databases.   
 
The two groups will be compared using a Student T test to evaluate for 
significant differences in the endpoints of each group.  
 
A 2 mean 2 sided power analysis was conducted assuming the mean VAS 
difference between groups to be 1.5. A sample size of 30 in each group 
will have 81% power to detect a difference in means of 1.500 assuming 
that the common standard deviation in 2.000 using a two group t-test with 
a 0.050 two-sided significance level. We anticipate using larger numbers 
to power subgroup analysis. 
 
Analysis between the two groups will involve a linear mixed effect model to 
compare the pain scales of the two groups over time. If vital signs are 
dissimilar at the beginning of the study, they will be controlled for prior to 
analysis. Pain medication requirement (determined by quantity of pills or 
mg used of same medication) will also be controlled within the analysis 
model.  Adjustments to the pain score within the groups due to pain 
medication usage will be performed. 
 
However, need for postoperative anti-emetic therapy is expected to be a 
somewhat rare event with similar means.  In a similar power analysis with 
an expected group A mean of 0.5 doses and group B mean of 1 dose with 
standard deviation of 1, a sample size of 63 is required to reach 
significance.  A somewhat large standard deviation is expected given the 
need for repeated dosing in those who do experience post-operative 
nausea 
 
Similarly, length of hospital stay is expected to be similar between the two 
groups.  The difference is generally expected to be between a “before 
lunch” or “after lunch” discharge on post-operative day 1. A two-group t 
test with a 0.05 two-sided significance level will be used to evaluate a 
difference in length of hospital stay. Therefore, a 2 mean 2 sided power 
analysis assuming group A mean hospital stay of 16 hours and group B 
mean stay of 18 hours with 4 hour standard deviation, a sample size of 63 
is required to achieve 80% power with p<0.05. 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 8 of 11 
     Revision: June 16, 2017 
 
 
  
j) Confidentiality 
All patient data will be deidentified prior to storage. Data will be 
stored in an encrypted electronic database. Only study personnel 
will have access to this database. No one will be permitted to store 
the database on a personal device.  The database will be stored 
exclusively on hospital network servers.  
 
 
k) Provisions to Monitor the Data to Ensure the Safety of 
subjects 
No significant risk is anticipated by the proposed study 
interventions.  All of the medications are currently in routine use at 
this institution. All adverse events related to study medication will 
be evaluated by the primary investigator.  A MIDAS report will be 
filed for any adverse event.  If there are any occurrences, an interim 
summary of adverse events will be compiled at 1 month and 
provided to the IRB. 
 
The study will be terminated immediately if study interventions 
result in subjects requiring intensive care interventions or death. 
 
 
 
l) Withdrawal of Subjects 
Subjects will be withdrawn from the study if there are any 
intraoperative surgical complications requiring deviation from 
standard technique.   
Subjects may withdraw from the study at any time 
11) 
Risks to Subjects 
Regional nerve block is an optional component of the standardly 
performed breast reduction at this institution.  Participation in the 
study does entail all the standard risks of this procedure.  These 
are primarily bleeding or bruising at the injection site, nerve 
damage resulting in pain, numbness or weakness, infection, and 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 9 of 11 
     Revision: June 16, 2017 
inadvertent systemic injection of the anesthetic.  There is a very 
small risk of pneumothorax.   
Primary additional risk to subjects compared to the standardly 
practiced block is allergic or adverse reaction to the study 
medication posed by the administration of dexamethasone.  
Adverse effects of this medication include behavioral disturbance, 
cardiac arrhythmia, hyperglycemia, and immune suppression.  
There is additional risk of increased postoperative pain due to 
deviation from standard nerve block procedure.  
  
12) 
Potential Benefits to Subjects 
Subjects may benefit from prolonged duration of local anesthesia 
resulting in enhanced postoperative pain control and decreased 
need for opiate analgesics. 
13) 
Privacy and Confidentiality 
All PHI will be removed prior to storage of any patient information.  PHI will 
not be shared with any research personnel or any other persons.  
Randomization status and all medications received will be disclosed to 
all healthcare personnel involved in the patient’s care while in the 
hospital.  The patient will not be informed of his or her study group.   
Patients will be completely informed of all privacy procedures as part of 
the consent process.  Study personnel will be available to answer 
questions throughout the duration of the study. 
 
14) 
Compensation for Research-Related Injury 
No compensation is available for research related injury 
15) 
Economic Burden to Subjects 
Subjects will not incur any costs by participating in this study 
16) 
Consent Process 
• Consent will be obtained following  “INVESTIGATOR 
GUIDANCE: Informed Consent (HRP-802).”  
• The study will be described in full to the patient during the pre-
operative clinic visit.  The patient will be provided with the 
consent form at this time for review.  If the patient is agreeable, 
written consent for the study will be obtained at this time.   
• Separate standard procedural consents will be obtained for the 
surgery itself and the regional nerve block as per current 
practice.  These will be obtained by the operating surgeon and 
anesthesiologist respectively. 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 10 of 11 
     Revision: June 16, 2017 
• Study personnel will again explain the details of the study to the 
patient upon arrival in the pre-operative holding area.  The 
patient will be given to opportunity to ask questions and 
participation in the study will be confirmed prior to leaving the 
holding area. 
Non-English Speaking Subjects 
• Spanish speaking subjects are also eligible for participation in 
the study.  Consent will be obtained using a Hospital-approved 
official interpreter 
• Subjects and the official interpreter will sign the Spanish Short 
Form consent after the full consent has been verbally translated 
to the subject  
• Patients who speak neither English nor Spanish are excluded 
Subjects who are not yet adults (infants, children, teenagers) 
• Minors will be excluded from participation in the study 
Cognitively Impaired Adults  
• Capacity to consent will be determined by the operating 
physician 
• Cognitively impaired adults are excluded from participation 
Adults Unable to Consent 
•  Adults unable to consent will be excluded 
17) 
Process to Document Consent in Writing 
Written consent will be obtained per “INVESTIGATOR GUIDANCE: 
Documentation of Informed Consent (HRP-803).”  
Vulnerable Populations 
Prisoners, pregnant women, minors, and adults unable to consent 
are excluded form participation in the study 
18) 
Drugs or Devices 
No non formulary drugs or devices are used in the study. All study 
medications will be stored per hospital pharmacy protocols 
19) 
Sharing of Results with Subjects 
Subjects will not receive individual results of this study 


Enhanced pain control after reduction mammaplasty with 
bupivacaine and dexamethasone regional block 
 
 
Page 11 of 11 
     Revision: June 16, 2017