A Volunteer Study to Determine the Anatomical Distribution of Injectate, the Extent of Sensory Block, and the Pharmacokinetics of Ropivacaine Following Erector Spinae Plane (ESP) Blocks.
Phase: PHASE4
Conditions: Distribution of Ropivacaine in Erector Spinae Plane Block
Sponsor: Milton S. Hershey Medical Center

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HRP-591 - Protocol for 
Human Subject Research
Protocol Title:  A volunteer study to determine the anatomical distribution of injectate, the extent of sensory 
block, and the pharmacokinetics of ropivacaine following Erector Spinae Plane (ESP) blocks.
Principal Investigator:
Name: Sanjib Adhikary, MD 
Department: Anesthesiology and Perioperative Medicine
Telephone: 717.531.6140
E-mail Address: sadhikary1@pennstatehealth.psu.edu
Version Date:
February 23, 2024
Clinicaltrials.gov Registration #:
NCT03476642
Table of Contents
1.0
Objectives
2.0
Background
3.0
Inclusion and Exclusion Criteria
4.0
Recruitment Methods
5.0
Consent Process and Documentation
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
7.0
Study Design and Procedures
8.0
Subject Numbers and Statistical Plan
9.0
Confidentiality, Privacy and Data Management
10.0
Data and Safety Monitoring Plan
11.0
Risks
12.0
Potential Benefits to Subjects and Others
13.0
Sharing Results with Subjects
14.0
Subject Stipend (Compensation) and/or Travel Reimbursements
15.0
Economic Burden to Subjects
16.0
Resources Available
17.0
Other Approvals
18.0
Multi-Site Research
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19.0
Adverse Event Reporting
20.0
Study Monitoring, Auditing and Inspecting
21.0
Future Undetermined Research: Data and Specimen Banking
22.0
    References
1.0
Objectives
1.1
Study Objectives
The primary objectives of this study are to define the extent of dermatomal anesthesia and 
anatomical spread of injectate (as defined by MRI imaging) that is provided by an ESP block at 
the T5 level, using twenty milliliters of 0.5% ropivacaine. MRI data will not be collected after 
May 2023
The secondary objectives include: 1) the measurement of changes in hemodynamic parameters 
associated with the ESP block, 2) the duration of sensory effects provided by ropivacaine with or 
without epinephrine, 3) the venous plasma concentration of ropivacaine at various time intervals 
after completion of the ESP block.
1.2
Primary Study Endpoints
Outcomes to be assessed
1.  Extent of dermatomal sensory loss
2.  Duration of sensory loss
3. Anatomical extent of injectate spread using MRI imaging. MRI data will not be collected after 
May 2023
4. Venous plasma concentration of ropivacaine at periodic time intervals
We are comparing these outcomes between
1. 20ml ropivacaine 0.5% with epinephrine vs no epinephrine
1.3
Secondary Study Endpoints
1.
Hemodynamic parameters at periodic time intervals
2.
Any adverse effects or side effects related to injection of the medications
2.0
Background 
2.1
Scientific Background and Gaps
Thoracic surgery is associated with significant postoperative pain and providing adequate 
analgesia in these patients is essential for enhanced recovery protocols1. Regional anesthesia 
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techniques, such as thoracic epidural and thoracic paravertebral blockade, are therefore 
commonly employed 2. These techniques have limitations however; they require a high degree of 
technical expertise, are contraindicated if the patient has a coagulopathy, and are associated with 
significant adverse effects and risk of complications. These include, but are not limited to 
hypotension, pneumothorax, and epidural abscess or hematoma formation. We recently 
described a novel ultrasound-guided regional anesthetic technique for providing thoracic 
analgesia, the ultrasound-guided Erector Spinae Plane (ESP) block. The ESP block involves 
injection of local anesthetic into the musculofascial plane deep (anterior) to the erector spinae 
muscle and superficial (posterior) to the tip of the transverse processes of the thoracic spine. Our 
radiological and anatomical investigation in fresh adult cadavers has shown that injection of a 
clinically-relevant volume (20ml) at the T5 vertebral level produces extensive spread of injectate 
within the erector spinae musculofascial plane, along the Para spinal and posterior chest wall, 
and extending between C4 and T12 vertebral levels 3. This corresponds with early clinical 
experience indicating that the ESP block is effective in treating chronic thoracic pain3, acute 
post-thoracic surgical pain 4-6, and pain from rib fractures 7. It thus appears to provide similar 
analgesia to a thoracic paravertebral block, while being technically simpler and safer to perform. 
The ESP block therefore has promise as a simple, safe, yet highly effective method of providing 
thoracic analgesia, and one that can be learned and performed by the majority of 
anesthesiologists. 
2.2
Previous Data
Ultrasound-guided ESP injections of a clinically relevant volume (20 mL) of normal saline (with 
iodinated contrast and methylene blue) at the T5 vertebral level were performed in fresh 
cadavers. The cadavers underwent computed tomography imaging and anatomical dissection. 
The radiological and anatomical findings demonstrated a distribution of injectate within the 
erector spinae musculofascial plane, along the Para spinal and posterior chest wall, and 
extending between C4 and T12 vertebral levels [4]. It is unclear how the extent of spread may 
have been influenced by the state of preservation of the cadaver, post mortem tissue desiccation, 
temperature difference, and lack of perfusion and respiratory motion that would be present in a 
living subject. Even though the ESP block has not been studied extensively for evaluation of 
mechanism of action, there are a number of case reports and case series that have been published 
in the last year, where ESP has been shown to be safe in different conditions of use. [4-6] To 
date, there are 39 manuscripts that have been published and indexed in PubMed, and no 
associated complications or side effects have been reported. A list of those publications can be 
found using the following link: 
https://www.ncbi.nlm.nih.gov/pubmed/?term=erector+spinae+plane+block. Here at the Penn 
State Hershey Medical Center, more than two hundred of these blocks have been performed for 
different procedures, without any complications or side effects.
2.3
Study Rationale
At present, no systematic investigation has been published that describes first, the spread of 
injectate following the ESP block in live human subjects; second, the extent of sensory blockade 
that can be reliably expected; and third, the pharmacokinetics of local anesthetic injected into 
this location. It is also unknown what effect additives such as epinephrine, might have on these 
parameters.  Epinephrine is commonly used for erector spinae plane blocks (ESP) or similar 
peripheral fascial plane injections to produce local vasoconstriction in order to prolong the action 
of the ropivacaine.  The current evidence for the mechanism of action and efficacy of the ESP 
block in providing sensory blockade of the thorax comes from cadaveric studies and small 
patient case series.[4-6] For this potentially valuable regional anesthesia technique to be adopted 
more widely in clinical practice, it is essential to determine, with more precision, the mechanism 
of action in live human subjects, and the extent of sensory blockade that can be reliably achieved 
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with clinically significant volumes of injectate boluses. Local anesthetic systemic toxicity, 
although rare, is always a concern in regional anesthesia and it is, therefore, also important from 
a safety perspective to determine the pharmacokinetics associated with the ESP block, so as to 
provide appropriate guidelines for maximum dose, volume and concentration of local anesthetic 
to be injected. In addition, this knowledge will provide baseline data from which to embark upon 
comparative studies with other more established techniques for regional anesthesia of the thorax, 
such as thoracic epidural or thoracic paravertebral blocks. A volunteer study in non-anesthetized 
subjects offers the most controlled setting to study these factors, as it eliminates the confounding 
effects of concomitant analgesic and anesthetic medications, surgical trauma, and patient co-
morbidities. 
3.0
Inclusion and Exclusion Criteria
3.1
Inclusion Criteria 
o
Healthy adults, male or female, aged 18 to 60 inclusive
o
Weight between 55 and 100 kg inclusive
o
Height 160 to190 cm inclusive
o
Normal baseline creatinine result
3.2
Exclusion Criteria
o
Pregnant females
o
Chronic medical condition requiring medication
o
History of previous major spinal, abdominal or thoracic surgery
o
Congenital abnormalities of the spine, back, thorax or abdomen
o
History of major trauma to the thorax or abdomen;
o
Allergy to ropivacaine or other amide local anesthetics
o
The presence of any metallic implant in their body
o
Any contraindication to magnetic resonance imaging as determined by completion of a 
standard questionnaire administered to all patients undergoing magnetic resonance imaging.  
(Does not apply after May 2023)
o
Individuals with any clinically relevant history or the presence of neurological deficits or 
cardiovascular disease
o
Trainees actively involved within the Department of Anesthesiology (e.g., fellows, students 
and residents)
3.3
Early Withdrawal of Subjects
3.3.1 Criteria for removal from study

Subject does not complete the study 

Develop any complications or side effects due to injections. 

Abnormal Creatinine level following baseline blood test

Subject does not follow fasting rules
3.3.2
Follow-up for withdrawn subjects
Any subject withdrawn from the study due to complications or side effects of the 
injection will be seen immediately by the PI and a course of treatment will be determined.
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4.0
Recruitment Methods
4.1
Identification of subjects
We will hang recruitment flyers
4.2
Recruitment process 
Healthy volunteers aged between 18yrs to 60 of both genders will be recruited with Recruitment 
Flyers. Interested subjects will be interviewed by the project coordinator from the Department of 
Anesthesia over the phone and will be advised to meet them at the Anesthesia clinic at a 
scheduled time. The informed written consent for the study will be obtained from them at the 
Anesthesia Clinic.
4.3
Recruitment materials
o
Recruitment Flyer
4.4
Eligibility/screening of subjects
Interested subjects will be interviewed by the project coordinator from the department of 
Anesthesia over phone using the attached IRB approved phone script and will be advised to meet 
them at the Anesthesia clinic at a scheduled time.
5.0
Consent Process and Documentation 
5.1
Consent Process 
 
5.1.1
Obtaining Informed Consent
5.1.1.1
Timing and Location of Consent
Consent to participate will be obtained from eligible patients after 
preoperative evaluation in the Anesthesia Preoperative Evaluation Clinic 
(APEC), during this visit blood will be drawn and sent to the clinical 
laboratory for measurement of kidney function as base line creatinine 
level. If the creatinine level is higher than normal they will be informed 
about it and excluded from the study.
5.1.1.2
Coercion or Undue Influence during Consent
The patient will be advised that participation in research studies is 
voluntary and that their decision to participate or not participate will not 
affect the level of care at this institution.
5.1.2
Waiver or alteration of the informed consent requirement
Not applicable
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5.2
Consent Documentation
5.2.1
Written Documentation of Consent
We will obtain a consent form signed by the patient and the person obtaining the consent. 
An original signed copy will be retained by the patient and the research team and a copy 
will be placed in the patient’s medical record.
5.2.2
Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.)
A waiver of documentation of consent is being requested for use of the phone screening 
process. During phone contact with a potential participant, verbal consent is obtained 
from the caller in order for the study coordinator to continue explaining the research 
study and asking pertinent eligibility questions.  If the caller is interested in participating 
in this study, a study visit will be scheduled.
5.3
Consent – Other Considerations 
After the consent is obtained, 1 ml of blood will be drawn and sent to the clinical laboratory for 
measurement of kidney function as base line creatinine level. Once the creatinine level is known 
and found to be within normal limits, they will be included in to the study. Once included they 
will be informed of the date and time of the study and advised to fast from solids for at least 6 
hours prior to the study, with clear liquid permitted until 2 hours before the procedure.
6.0
HIPAA Research Authorization and/or Waiver or Alteration of Authorization
6.1
Authorization and/or Waiver or Alteration of Authorization for the Uses and 
Disclosures of PHI
Check all that apply:
 
Not applicable, no identifiable protected health information (PHI) is accessed, used 
or disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable]
Authorization will be obtained and documented as part of the consent process. [If 
this is the only box checked, mark sections 6.2 and 6.3 as not applicable]
Partial waiver is requested for recruitment purposes only (Check this box if 
patients’ medical records will be accessed to determine eligibility before 
consent/authorization has been obtained). [Complete all parts of sections 6.2 and 6.3]
Full waiver is requested for entire research study (e.g., medical record review 
studies). [Complete all parts of sections 6.2 and 6.3]
Alteration is requested to waive requirement for written documentation of 
authorization (verbal authorization will be obtained). [Complete all parts of sections 
6.2 and 6.3]
6.2
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI
6.2.1
Access, use or disclosure of PHI representing no more than a minimal risk to 
the privacy of the individual
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6.2.1.1 Plan to protect PHI from improper use or disclosure
Information is included in the “Confidentiality, Privacy and Data 
Management” section of this protocol.
6.2.1.2 Plan to destroy identifiers or a justification for retaining identifiers 
Identifiers will be destroyed when the study has been completed and the 
results published.
6.2.2
Explanation for why the research could not practicably be conducted without 
access to and use of PHI
Information must be obtained either from the subject’s electronic medical record or self-
reported physical history during recruitment to determine eligibility
6.2.3
Explanation for why the research could not practicably be conducted without 
the waiver or alteration of authorization
The waiver is requested only for recruitment to determine subject eligibility to ensure that 
no medical conditions that fall into the exclusion criteria are present and would thus 
preclude enrollment.  This waiver will minimize the enrollment of subjects’ who may 
ultimately fail to meet the study inclusion/exclusion criteria.
6.3
Waiver or alteration of authorization statements of agreement
Protected health information obtained as part of this research will not be reused or disclosed to 
any other person or entity, except as required by law, for authorized oversight of the research 
study, or for other permitted uses and disclosures according to federal regulations. 
The research team will collect only information essential to the study and in accord with the 
‘Minimum Necessary’ standard (information reasonably necessary to accomplish the 
objectives of the research) per federal regulations. 
Access to the information will be limited, to the greatest extent possible, within the research 
team. All disclosures or releases of identifiable information granted under this waiver will be 
accounted for and documented.
7.0
Study Design and Procedures
7.1
Study Design
This will be a randomized, blinded, controlled study. 
This study will examine the effects of single injections of 0.5% ropivacaine with 
epinephrine or without epinephrine (20 ml of each) injected at ESP at the T5 vertebra 
level.
7.1.1
Randomization process
The subjects enrolled will be randomized into two groups (6 participants in each group) by a 
computer-generated randomization list using SAS software (SAS Institute, Cary, NC):
Randomization groups
 
1. Group RE will have 20mL of 0.5% Ropivacaine with epinephrine injected at the left or right 
T5 transverse process. 
2. Group R will have 20mL of 0.5% Ropivacaine without epinephrine injected at the left or 
right T5 transverse process. 
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The randomization will be performed, using a sealed envelope technique, and will be stratified 
according to the side of the injections (either left or right) so that each arm will have equal 
number of left and right sided ESP blocks. This will be done by the investigational pharmacy 
while preparing the medications. All subjects, the anesthesiologist performing the procedure, the 
radiologist, and the research coordinator collecting the data will be blinded and will not be aware 
of the details of the injection and allocation of the participants. In the event that the patient has a 
concerning reaction or becomes unstable in any fashion, the patient will be immediately 
unblinded and removed from the study.
.
The conduct of the study will be as follows.
7.2
Study Procedures
7.2.1
Pre-Procedure Visit
This visit will take place at the Anesthesia Preoperative Evaluation Clinic (APEC) for pre-
procedural evaluation.
At this visit:
o
Consent to participate will be obtained from eligible patients
o
Blood will be drawn for baseline creatinine level
o
All subjects will be instructed to fast from solids for at least 6 hours prior 
to the study, with clear liquid permitted until 2 hours before the procedure.
The blood collected for the creatinine level will be taken in person by the research 
coordinator to the clinical lab of Hershey Medical center. The samples will be destroyed 
immediately after the required amount of blood is tested. The results of the creatinine test 
will be sent to PI and that will determine the inclusion of the subject in the study.
Day of Procedure - (n=12)
 The procedure will be scheduled at least 24 hr. after the pre-procedure visit. On the day 
of the procedure, the investigational pharmacy will prepare the syringe according to the 
randomization. The appropriate study medication will be picked up by the coordinator at 
the investigational pharmacy. The appearance of the syringe will be the same regardless 
of the medication that is inside.  The study physician will use the randomization number 
as generated by investigational pharmacy to determine on which side to place the block 
and allocate a study number. Subjects and outcome assessors will be blinded to 
randomization allocation.
Study subjects will report to the Clinical Research Center (CRC) of Milton S. Hershey 
hospital on the day of their scheduled study procedure.  Once they are checked in to CRC 
and ascertained that they followed fasting instructions, the female participants will be 
asked to take pregnancy test using a urine sample and a standardized pregnancy testing 
kit. Once the pregnancy test is determined to be negative, they will be considered to be a 
study participant. If pregnancy test is positive, they will be excluded from the study. 
Once the participant is included in to the study, an intravenous access and continuous 
monitoring of vital signs (ECG, non-invasive blood pressure every 5 minutes, and pulse 
oximetry) will be established.  3 ml of blood will be obtained from the Intravenous line 
already placed in the subject prior to performing the block. These samples will be 
repeated at 20, 40, 60, 90, 120, and 240 minutes after completion of the injection of 
active drug. A member of the research team will manually transport the appropriately-
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labeled blood collection tube to a storage freezer in the Perioperative Genomics 
Laboratory (C2813, C2848) during the transport, blood samples will be placed in 
Category A sealed triple packaging. During transport, the specimen tubes will be placed 
in splash-proof and leak-proof containers. These primary containers are placed inside of 
secondary containers which will be sealed. The blood samples will be processed and 
analyzed for ropivacaine level using HPLC at genomic laboratory of department of 
Anesthesia, Hershey medical center at a later date. The results of the level of the 
ropivacaine level will be used for analysis of the results for the study. The subjects will 
not receive the results of these tests. However, if any of the subjects if specifically 
request for the results of these test that will be given to them. The blood samples will be 
immediately destroyed after the results of the ropivacine conc. in the samples is obtained. 
The additional blood from samples, if any, will be destroyed. 
The subject will be placed in a sitting position, the skin over their upper back will be 
disinfected with chlorhexidine 2%, and the tip of the T5 transverse process on one side 
will be identified using a low-frequency curvilinear ultrasound transducer (Sonosite, 
Bethesda, USA) placed in a longitudinal parasagittal orientation as previously described. 
[4] The skin over the needle insertion site will be anesthetized with 2ml of lidocaine 1% 
conc. for patient comfort. A 22-gauge 10cm Tuohy needle (Stimuplex, BBraun, and 
Bethlehem, USA) will be inserted in-plane with the ultrasound beam to contact the T5 
transverse process. One ml of 0.9% normal saline will be injected to confirm correct 
needle tip placement separating the ESP from transverse process, as evidenced by visible 
linear fluid spread deep to the erector spinae muscle.  Injection of the specific volume and 
type of fluid according to the randomization group (see above) will then take place.  MRI 
part of study stopped May 2023. After the completion of the assigned injection they will 
be transported to the MRI suite at the MRI core facility on the Hershey campus in a 
wheel chair.  The subject will undergo two MRI’s to determine the spread of the 
anesthetic. These will take place at approximately 30 and 90 minutes following the 
completion of the assigned block.  
Following the Block injection (completion of the MRI data May 2023), the subjects will 
be allowed to sit, stand or lay down for the remainder of the study. Continuous 
monitoring and recording of vital signs will take place as, blood pressure and heart rate 
will be measured every 5 minutes, starting prior to performing the block, till 60 minutes 
after the block is performed and every 15 minutes thereafter for the duration of the study. 
A member of the research team blinded to the randomization allocation will perform a 
sensory assessment for loss of sensation to cold using ethanol on the skin at 20, 60, 120, 
240, and 360 mins after the injection of active drug. The extent of sensory loss to cold 
will be marked on the body using a water-soluble color marker each time and will be 
photographed each time interval. A binary scoring system will be used for both 
assessments:  1 = reduced sensation; 2 = normal sensation. 
Once the final sensory assessment has been completed (360 minutes following block), the 
subject will remain for an additional 30 minutes of observation. The intravenous cannula 
will be removed and the subject will then be discharged to return home. The subjects will 
be discharged from the research facility with a note to inform the PI or Research 
coordinator if they feel anything different or abnormal. The subject should not drive for 
24 h after receiving the block, and will need to have someone to drive them home after 
the procedure.
7.3
Duration of Participation
It will take three days to complete this research study.  For two consecutive days 
following the procedure they will be asked to participate in a follow-up phone call to 
discuss how they are feeling. The script for the follow-up phone call is attached.
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7.4
Test Article(s) (Study Drug(s) and/or Study Device(s))
7.4.1 Description
The group receiving the ropivacaine 0.5% will receive 1 syringe containing 20mLs of 
ropivacaine 0.5%, and the group receiving the ropivacaine/epinephrine will receive 1 
syringe containing 19.9mLs of ropivacaine 0.5% and 0.1 mLs of Epinephrine 1mg/mL 
for a total volume of 20mLs. The medications will be injected between muscle planes in 
the back using real time ultra sound guidance. Both medications have been approved by 
the FDA for many years, for this specific use, as well as for injection around nerve fibers. 
These medications have been used in billions of people in the world already, with a very 
robust safety record. In our institution, we use these medications routinely every day for a 
number of procedures, including ESP blocks.
7.4.2 Treatment Regimen
There will be no adjustment to dose. Every participant will receive the same amount of 
medications as prepared by the investigational Pharmacy. The medications will be 
injected using real time ultra sound guidance between two muscle planes in the back of 
the body, using a 22gauge needle.
7.4.3 Method for Assigning Subject to Treatment Groups
The subjects enrolled will be randomized into two groups by a computer-generated 
randomization list using SAS software (SAS Institute, Cary, NC):
Randomization groups
 
1. Group RE will have 20mL of 0.5% Ropivacaine with epinephrine injected at 
the left or right T5 transverse process. 
2. Group R will have 20mL of 0.5% Ropivacaine without epinephrine injected 
at the left or right T5 transverse process. 
7.4.4 Subject Compliance Monitoring
The study will be done in the CRC of the Penn State College of Medicine. (and the MRI 
suit of the Department of Radiology, where the MRI will be done. Completed May 2023) 
Once the participant is included in to the study, an intravenous access and continuous 
monitoring of vital signs (ECG, non-invasive blood pressure every 5 minutes, and pulse 
oximetry) will be established. Continuous monitoring and recording of vital signs will 
take place as follows: blood pressure and heart rate will be measured every 5 minutes, 
starting prior to performing the block, till 60 minutes after the block is performed, and 
every 15 minutes thereafter for the duration of the study.
7.4.5 Blinding of the Test Article
The randomization will be performed, using a sealed envelope technique, by the 
investigational pharmacy while preparing the medications. All subjects, the 
anesthesiologist performing the procedure, the radiologist, and the research coordinator 
collecting the data will be blinded and will not be aware of the details of the injection and 
allocation of the participants. In the event that the patient has a concerning reaction or 
becomes unstable in any fashion, the patient will be immediately unblinded and removed 
from the study.
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7.4.6 Receiving, Storage, Dispensing and Return 
7.4.6.1 Receipt of Test Article 
The study drug will be prepared and dispensed in standard sterile way by 
the Investigational Pharmacy of the Milton S. Hershey medical center. The 
medications will be collected, by the study coordinator, in a container with 
the participant’s number, and will be brought to the CRC on the day of the 
study prior to the administration of medications for the study.
7.4.6.2
Storage
Investigational Pharmacy personnel, study coordinator and investigator 
will only have access to the medications and there will not be any storage 
of the medications.
7.4.6.3
Preparation and Dispensing
The randomization will be performed, using a sealed envelope technique, 
by the investigational pharmacy while preparing the medications.
7.4.6.4 Return or Destruction of the Test Article
NA
7.4.6.5  Prior and Concomitant Therapy
None 
8.0
Subject Numbers and Statistical Plan
8.1
Number of Subjects
12 subjects are needed to follow the study protocol through to completion. Up to 35 subjects may 
be enrolled to allow for loss of participants who complete the enrollment step, but do not proceed 
to receive the ESP block procedure.
8.2
Sample size determination 
This is a pilot study and will use descriptive results of this study to plan for a larger randomized 
clinical trial in the future.
8.3
Statistical methods
Statistics: The statistical analysis will be performed using STATA 14.1 statistical software 
(StataCorp LP, College Station, TX) and Wilcoxon matched-pairs U test will be utilized for 
different MRI measurements and calculations. The 2 test will be used to analyze the differences 
between dermatomal anesthesia on hemi-thorax and abdomen. 
9.0
Confidentiality, Privacy and Data Management 
See the Research Data Plan Review Form. 
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10.0
Data and Safety Monitoring Plan
10.1
Periodic evaluation of data
The PI and research coordinator will review cumulative adverse events, early termination of 
study participation, and accrual every six months and report any issues requiring modification of 
the study or alteration of the risk: benefit ratio to the IRB immediately.  A summary of adverse 
events, study progress and protocol modifications will be included for IRB review in the 
continuing review.
10.2
Data that are reviewed
The data to be reviewed will be:

Safety data

Untoward events

Efficacy data
10.3
Method of collection of safety information
Safety information will be collected by the research coordinator at study visits and follow-up 
phone call. 
10.4
Frequency of data collection
See table below
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Frequency of data collection, including when safety data 
collection starts
Conse
nt
Placeme
nt of IV
Collecti
on of 
blood 
samples
MRI
Remov
e May 
2023
Monitori
ng of 
Vitals
Phon
e 
calls
Senso
ry
Evals
Pre 
Procedure 
Visit
X
X
On Arrival
X
X
X
5mts
X
10
X
15
X
20
X
X
X
25
X
30
X
X
35
X
40
X
X
45
X
50
X
55
X
60
X
X
X
75
X
90
X
X
X
105
X
120
X
X
X
135
X
150
X
165
X
180
X
195
X
210
X
The day of Procedure
225
X
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10.5
Individuals reviewing the data
Oversight for the conduct of the study will be provided by the PI and the research coordinator 
will monitor the data. They will ensure that all eligible criteria and consent requirements are met 
prior to a subjects’ participation in the study and that the procedures and adverse event reporting 
occur according to the IRB approved protocol.
10.6
Frequency of review of cumulative data
The PI and research coordinator will review cumulative adverse events, early termination of 
study participation, and accrual every six months and report any issues requiring modification of 
the study or alteration of the risk: benefit ratio to the IRB immediately.  A summary of adverse 
events, study progress and protocol modifications will be included for IRB review in the 
continuing review.
10.7
Statistical tests
Not applicable
10.8
Suspension of research
The study will be immediately suspended if there is any report or occurrence of serious side 
effect to any of the subjects. The serious side effects include but not limited to Infection, sepsis, 
severe hypotension, severe hypertension, any condition requiring to air way management,  
11.0
Risks
The risks to you include:
240
X
X
X
255
X
270
X
285
X
300
X
315
X
330
X
345
X
360
X
X
Post 
Procedure 
Day 1
X
Post 
Procedure 
Day 2
X
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Venipuncture:  The discomfort associated with removing blood by venipuncture (by needle from a 
vein) is a slight pinch or pin prick when the sterile needle enters the skin. The risks include mild 
discomfort and/or a black and blue mark at the site of puncture. Less common risks include a small 
blood clot, infection or bleeding at the puncture site, and on rare occasions fainting during the 
procedure.
Regional Anesthesia - Possible complications and discomforts from regional anesthesia include:
• Common – local/pain and/or discomfort, infection, and/ or headache
• Uncommon – shock or extreme fall in blood pressure, convulsions and/or seizures
• Rare – nerve damage resulting in numbness, tingling and/or paralysis which may be temporary 
or permanent. Respiratory arrest, cardiac arrest, and/or allergic reaction to drugs. Death.
Ropivacaine Hydrochloride:  Possible complications and discomforts from ropivacaine hydrochloride 
include:
• Incidence 5% or greater – High blood pressure, nausea, vomiting, fever, headache, back pain, 
low blood pressure, and slow heartbeat. 
• Incidence 1% to 5% - Urinary retention, dizziness, shaking or exaggerated shivering, rapid 
heart rate, anxiety, production of abnormally small amounts of urine, reduced sense of touch or 
sensation, chest pain, deficiency of potassium in the bloodstream.
Epinephrine: 
• Side effects of epinephrine include: Fast heartbeat, sweating, headache, weakness, shakiness, 
paleness, and dizziness.
Procedural risks: 
• It will involve the similar procedural risk as other peripheral regional anesthesia procedures. 
This procedure has not been studied very extensively so the literature of its safety is not known 
completely. However, there are a number of case reports and case series that have been 
published in the last year, where ESP has been shown to be safe in different conditions of use.[4-
6] Here at the Penn State Hershey Medical Center, more than two hundred of these blocks have 
been performed for different procedures, without any complications or side effects.
• There is a rare risk of pneumothorax, which is getting air or gas in the cavity between the lungs 
and the chest wall, causing collapse of the lung.
• Venipuncture: Any time we insert a needle in your body there is a minimal risk for bruise, 
infection or extravasation of blood.
MRI removed May 2023
MRI discomfort and risks -- Because the MRI scanner contains a very strong magnet, you may not be 
able to have the MRI if you have certain kinds of metal in your body (for example, a heart pacemaker, a 
metal plate, certain types of heart valves or brain aneurysm clips). Someone will ask you questions about 
this before you have the MRI. Having a MRI may mean some added discomfort to you. In particular, 
you may be uncomfortable inside the MRI scanner if you do not like to be in closed spaces 
(“claustrophobia”). You may also be bothered by the loud banging noise during the study. Temporary 
hearing loss has been reported from the loud noise. This is why you will be asked to wear earplugs. 
During the procedure, you will be able to talk with the MRI staff through a speaker system. You can tell 
them to stop the scan at any time.
You should not expect to get your results from the MRI scan since the scan done during this study is not 
designed to detect or evaluate any medical condition you may have. The MRI scan is intended solely for 
research purposes and will not provide the same detailed information as an MRI done for clinical 
reasons. There is a small chance that researchers could find something that might be important to your 
health. If this happens, a member of the study team may contact you to find out if you would like to 
learn more. However, even if we find something important to your health, we cannot guarantee that you 
will be contacted. 
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Risk of loss of confidentiality: There is a risk of loss of confidentiality if your information or your 
identity is obtained by someone other than the investigators, but precautions will be taken to prevent this 
from happening. The confidentiality of your electronic data, created by you or by the researchers, will be 
maintained to the degree permitted by the technology used. Absolute confidentiality cannot be 
guaranteed.
12.0
Potential Benefits to Subjects and Others
12.1
Potential Benefits to Subjects
You will not experience any direct benefit from this research. 
12.2
Potential Benefits to Others
Presently there is no outcome and other related data available for this procedure.  The results of this 
research may guide the future use of ESP Blocks by providing providers with a better 
understanding of the technique and its associated effect and may help improve the practice of ESP 
blocks for patients in the future. 
13.0
Sharing Results with Subjects
Results will not be shared with the participants.
14.0
Subject Stipend (Compensation) and/or Travel Reimbursements
Participants will receive $300 for the time they have given for participation in this research study. If they 
do not complete the study for any reason, they will be paid for the visits they have completed: 
15.0
Economic Burden to Subjects
15.1
Costs 
There is no cost to participants for taking part in this study. 
15.2
Compensation for research-related injury
It is the policy of the institution to provide neither financial compensation nor free medical 
treatment for research-related injury. In the event of injury resulting from this research, medical 
treatment is available but will be provided at the usual charge. Costs for the treatment of 
research-related injuries will be charged to subjects or their insurance carriers.
16.0
Resources Available
16.1
Facilities and locations
The research will be conducted at the Hershey Medical Center‘s Clinical Research Center.
16.2
Feasibility of recruiting the required number of subjects
We will be using flyers to recruit patients.
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16.3
PI Time devoted to conducting the research
PI has academic time that he can use to perform the research, and he is available when onsite. 
16.4
Availability of medical or psychological resources
Not applicable.
16.5
Process for informing Study Team
Meetings will be held periodically as needed to ensure all research team members are informed 
about the protocol and their duties. Team emails will also be used to keep team members 
updated.
17.0
Other Approvals
17.1
Other Approvals from External Entities
Not applicable
17.2
Internal PSU Committee Approvals
Check all that apply:
  Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of 
pathologic specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the 
“Supporting Documents” page in CATS IRB. This form is available in the CATS IRB 
Library.  
  Animal Care and Use – All campuses – Human research involves animals and humans or the 
use of human tissues in animals
  Biosafety – All campuses – Research involves biohazardous materials (human biological 
specimens in a PSU research lab, biological toxins, carcinogens, infectious agents, 
recombinant viruses or DNA or gene therapy).
  Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes 
of body fluid specimens for research purposes by the Clinical Laboratories; and/or use of 
body fluids that had been collected for clinical purposes, but are no longer needed for clinical 
use. Upload a copy of HRP-901 - Human Body Fluids for Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library. 
  Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves 
the use of CRC services in any way.
  Conflict of Interest Review – All campuses – Research has one or more of study team 
members indicated as having a financial interest.
  Radiation Safety – Hershey only – Research involves research-related radiation procedures. 
All research involving radiation procedures (standard of care and/or research-related) must 
upload a copy of HRP-903 - Radiation Review Form on the “Supporting Documents” page in 
CATS IRB. This form is available in the CATS IRB Library.
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  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or 
IDE or intends to hold the IND or IDE.
  Scientific Review – Hershey only – All investigator-written research studies requiring 
review by the convened IRB must provide documentation of scientific review with the IRB 
submission. The scientific review requirement may be fulfilled by one of the following: (1) 
external peer-review process; (2) department/institute scientific review committee; or (3) 
scientific review by the Clinical Research Center Advisory committee.  NOTE: Review by 
the Penn State Hershey Cancer Institute Scientific Review Committee is required if the study 
involves cancer prevention studies or cancer patients, records and/or tissues. For more 
information about this requirement see the IRB website at: 
http://www.pennstatehershey.org/web/irb/home/resources/investigator 
17.0
Multi-Site Research
Not applicable
19.0
Adverse Event Reporting
19.1
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
In accordance with applicable policies of The Pennsylvania State University Institutional Review 
Board (IRB), the investigator will report, to the IRB, any observed or reported harm (adverse 
event) experienced by a subject or other individual, which in the opinion of the investigator is 
determined to be (1) unexpected; and (2) probably related to the research procedures. Harms 
(adverse events) will be submitted to the IRB in accordance with the IRB policies and 
procedures.
20.0
Study Monitoring, Auditing and Inspecting
20.1
Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the Penn State 
quality assurance program office(s), IRB, the sponsor, and government regulatory bodies, of all 
study related documents (e.g., source documents, regulatory documents, data collection 
instruments, study data etc.).  The investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g., pharmacy, diagnostic laboratory, etc.).
21.0
Future Undetermined Research: Data and Specimen Banking
Not applicable. 
22.0
References
1.
Romero, A., J.E. Garcia, and G.P. Joshi, The state of the art in preventing postthoracotomy pain. 
Semin Thorac Cardiovasc Surg, 2013. 25(2): p. 116-24.
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2.
Bottiger, B.A., S.A. Esper, and M. Stafford-Smith, Pain management strategies for thoracotomy 
and thoracic pain syndromes. Semin Cardiothorac Vasc Anesth, 2014. 18(1): p. 45-56.
3.
Joshi, G.P., et al., A systematic review of randomized trials evaluating regional techniques for 
postthoracotomy analgesia. Anesth Analg, 2008. 107(3): p. 1026-40.
4.
Forero, M., et al., The Erector Spinae Plane Block: A Novel Analgesic Technique in Thoracic 
Neuropathic Pain. Reg Anesth Pain Med, 2016. 41(5): p. 621-7.
5.
Forero M. Rajarathinam M. Adhikary S, C.K., Continuous Erector Spinae Plane Block for 
Rescue Analgesia in Thoracotomy After Epidural Failure. Anesthesia & Analgesia case reports, 
2017.
6.
Chin, K.J., et al., The analgesic efficacy of pre-operative bilateral erector spinae plane (ESP) 
blocks in patients having ventral hernia repair. Anaesthesia, 2017. 72(4): p. 452-460.
7.
Borglum, J., et al., Distribution patterns, dermatomal anesthesia, and ropivacaine serum 
concentrations after bilateral dual transversus abdominis plane block. Reg Anesth Pain Med, 
2012. 37(3): p. 294-301.
8.
Rifai, N., et al., Simultaneous measurement of plasma ropivacaine and bupivacaine 
concentrations by HPLC with UV detection. Ther Drug Monit, 2001. 23(2): p. 182-6.
9.
Tanaka, E., et al., Simultaneous determination of three local anesthetic drugs from the 
pipecoloxylidide group in human serum by high-performance liquid chromatography. J 
Chromatogr B Analyt Technol Biomed Life Sci, 2006. 834(1-2): p. 213-6.
10. 
American College of Radiology, Manual on Contrast media.  2017.  ISBN: 978-1-55903-012-0
11. 
Schulte-Altedorneburg G et al.  MR arthrography: pharmacology, efficacy and safety in clinical 
trials.Skeletal Radiol. 2003;32 (1):1-12
12. 
Hunt H et al.  Frequency and severity of adverse effects of iodinated and gadolinium contrast 
materials:  Retrospective review of 356, 930 doses.  AJR 2009; 193: 1124-1127.
13. 
Wittich C. et al.  Ten Common Questions (and Their Answers) About Off-label Drug Use.  
Mayo Clin Proc. 2012;87:982-990
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