Evaluation of Diaphragm Movement After an Interscalene Block
Phase: PHASE4
Conditions: Phrenic Nerve Paralysis
Sponsor: University of Minnesota

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
Page 1 of 14 
Revised: 1/19/2018 
 
 
 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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Revised: 1/19/2018 
Protocol Title 
Evaluation of diaphragm movement after an Interscalene block 
Principal 
Investigator/Faculty 
Advisor 
Name: Jason Habeck 
Department: Anesthesiology 
Telephone Number: 612-624-9990 
Email Address: habe0073@umn.edu 
Student 
Investigator 
Name: 
Current Academic Status (Student, Fellow, Resident): 
  
Department: 
Telephone Number: 
Institutional Email Address: 
Scientific 
Assessment 
 
IND/IDE # (if 
applicable) 
n/a 
IND/IDE Holder 
n/a 
Investigational Drug 
Services # (if 
applicable) 
n/a 
Version 
Number/Date: 
3 5/9/2019 
 
PROTOCOL COVER PAGE 
 
 
 
 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
Page 3 of 14 
Revised: 1/19/2018 
 
REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
3 
5/9/19 
Adjusted inclusion criteria to 
include those who are not enrolled 
in the TSA study.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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Revised: 1/19/2018 
1.0 
Table of Contents 
 
1.0 
Objectives 
7 
2.0 
Background 
7 
3.0 
Study Endpoints/Events/Outcomes 
7 
4.0 
Study Intervention(s)/Investigational Agent(s) 
7 
5.0 
Procedures Involved 
8 
6.0 
Data and Specimen Banking 
9 
7.0 
Sharing of Results with Participants 
9 
8.0 
Study Population 
10 
9.0 
Vulnerable Populations 
10 
10.0 Local Number of Participants 
11 
11.0 Local Recruitment Methods 
11 
12.0 Withdrawal of Participants 
13 
13.0 Risks to Participants 
13 
14.0 Potential Benefits to Participants 
13 
15.0 Statistical Considerations 
13 
16.0 Confidentiality 
14 
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
14 
18.0 Provisions to Protect the Privacy Interests of Participants 
15 
19.0 Compensation for Research-Related Injury 
15 
20.0 Consent Process 
16 
21.0 Setting 
19 
22.0 Multi-Site Research 
19 
23.0 Resources Available 
20 
24.0 References 
21 
 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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Revised: 1/19/2018 
ABBREVIATIONS/DEFINITIONS 
● LB liposome bupivacaine 
● ISB interscalene block 
● TSA total shoulder arthroplasty 
● RCR rotator cuff surgery 
 
 
 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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2.0 
Objectives 
2.1 Purpose: To evaluate the movement of the diaphragm after an interscalene 
block with liposome bupivacaine (LB) compared to interscalene block (IB) 
with bupivacaine.  This study will evaluate if there is a possible prolonged 
phrenic nerve paralysis when using liposome bupivacaine in an interscalene 
block, using ultrasound.  
3.0 
Background 
3.1 Significance of Research Question/Purpose: To date there is no previous 
study looking at diaphragm movement after an Liposomal Bupivacaine 
Interscalene Block.  It is important to see how long the phrenic nerve is 
affected by this block if at all.   
3.2 Preliminary Data: We have not routinely examined that patient’s diaphragm 
via ultrasound after ISB at M Health.   Patients have not been readmitted 
for breathing problems with our current practice.  
3.3 Existing Literature: There is no previous literature in LB ISB.  Urmey et al. 
showed 100% phrenic nerve block post ISB. But others (Renes et al) have 
evaluated it using bupivacaine and found that lower doses resulted in less 
diaphragm blockade. Cuvillon showed that those with a catheter had 66% 
phrenic nerve paralysis at 24 hours.  
4.0 
Study Endpoints/Events/Outcomes 
4.1 Primary Endpoint/Event/Outcome: The primary study endpoint will be 
diaphragm excursion (movement in cm) from rest to sigh in a sitting 
position.  
4.2 Secondary Endpoint(s)/Event(s)/Outcome(s): The secondary endpoint will 
be the diaphragm excursion (movement in cm) from rest to a quick 
inspiratory breath.  
4.3 Secondary Endpoint(s)/Event(s)/Outcome(s): Evaluation of baseline FEV1, 
FVC (or FEV6) and FEV1/FVC ratio via spirometry. 
5.0 
Study Intervention(s)/Investigational Agent(s) 
5.1 Description: This study will be run concurrently with two other studies 
comparing bupivacaine to Liposomal Bupivacaine in shoulder surgeries. We 
will either use already randomized patients for our randomization process or 
if they are not enrolled in either RCR or TSA study we will randomize them 
to one of the two groups. For this study in particular we will use an 
ultrasound machine to scan the diaphragm of any patient who had an 
Interscalene Block for Total Shoulder Arthroplasy or Rotator Cuff Repair. 
Patients are to be scanned in an upright sitting position and scanned from a 
low intercostal or subcostal approach using the liver or spleen as an acoustic 
window. M Mode will be applied and the range of diaphragmatic movement 
from the resting expiratory position to deep inspiration (sigh test) will be 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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recorded as was the range of diaphragmatic movement from resting 
expiratory position when quickly inspiring through the nose (sniff test). The 
blocks will be done regardless of the study as they are standard of care for 
pain control.  The only intervention is ultrasound examination of the 
patient’s diaphragm at baseline, 3 hours post block in recovery room and on 
post-operative day 1, and basic spirometry to record FEV1 and FVC via a 
portable spirometer at the same time points.  If patients did stay in hospital 
on postoperative day 2 we would also evaluate their diaphragm function.   
5.2 Drug/Device Handling: n/a 
5.3 Biosafety: n/a  
5.4 Stem Cells: n/a 
 
6.0 
Procedures Involved 
6.1 Study Design: This is a prospective  study 
Study Procedures: All patients who are enrolled in our TSA or RCR studys fit the criteria 
of being scheduled for overnight shoulder surgery and having an ISB with or without LB. 
The patients will already be randomized into either an ISB with bupivacaine or with 
bupivacaine and LB. If the patient is not enrolled or does not fit inclusion criteria for the 
RCR or TSA study they will then be randomized to either bupivacaine or liposome 
bupivacaine ISB.  The patients will perform spirometry (one large exhale into a 
spirometer) and have an ultrasound examination of their diaphragm at baseline prior to 
the block, in PACU after their procedure, and on postoperative day 1 (24 hours after 
ISB).  Diaphragmatic movement will be evaluated by real-time M-mode ultrasonography 
of the hemidiaphragm using a 17-mm 1- to 5-MHz broadband phased array US probe. 
Patients are to be scanned in an upright sitting position and scanned from a low 
intercostal or subcostal approach using the liver or spleen as an acoustic window. M 
Mode will be applied and the range of diaphragmatic movement from the resting 
expiratory position to deep inspiration (sigh test) will be recorded as well as the range of 
diaphragmatic movement from resting expiratory position when quickly inspiring 
through the nose (sniff test). This will occur three times, at baseline prior to surgery, in 
the recovery room, and on the ward on postoperative day 1. All nerve blocks will be 
confirmed to be functional via a sensory skin test prior to surgery or in the recovery room 
prior to the recovery room evaluation. 
6.2 Study Duration: The patients will be in the study for 2 days.  The duration of 
the study should be 3 months to enroll the 22 patients.  
6.3 Individually Identifiable Health Information: PHI will be recorded but once 
data collection is done then the phi will be removed and replaced with 
unique identifier.  This is just to ensure we see the correct patient for the 
data collection.   
6.4 Use of radiation: n/a  
6.5 Use of Center for Magnetic Resonance Research: n/a  
7.0 
Data and Specimen Banking 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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7.1 Storage and Access: the data will be kept in the University box.  Data is kept 
for 7 years.   
7.2 Data: The data kept will be patient demographics such as weight, BMI, age, 
sex.  Also, block medications and volume used, time of injection, surgical 
procedure, range of diaphragm movement at baseline, in recovery room, and 
on postoperative day 1 and spirometry at baseline, in recovery and 
postoperative day 1.  
7.3 Release/Sharing: data will be kept with the PI and co-I 
8.0 
Sharing of Results with Participants 
8.1    No results will be shared with participants.  
9.0 
Study Population 
9.1 Inclusion Criteria: All patients age 18 years and older who are scheduled for  
shoulder surgery with interscalene block and remain in the hospital for more 
than 24 hours that are being randomized into a bupivacaine versus LB ISB 
block study or those who are not enrolled in the TSA or RCR study but are 
having shoulder surgery with ISB and planned to spend one night in the 
hospital.   
9.2 Exclusion Criteria: Non-English speaking patients.  
9.3 Screening: On the week to day prior to surgery patients will be identified 
from surgical case list.  Then prior to or on day of surgery patients will be 
asked to participate in the study and given enough time to decide to 
participate and ask questions.  
10.0 Vulnerable Populations 
10.1 Vulnerable Populations:  
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished capacity 
to consent, including, but not limited to, those with acute medical 
conditions, psychiatric disorders, neurologic disorders, developmental 
disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
x None of the above 
10.2 Additional Safeguards:  
11.0 Local Number of Participants 
11.1 Local Number of Participants to be Consented: 40 patients consented with 
goal of 22 patients enrolled in the study 
12.0 Local Recruitment Methods 
12.1 Recruitment Process: No recruitment posters.  Only recruit from surgical 
lists. Patients will be recruited from the group of adult surgical patients at 
the University of Minnesota undergoing shoulder surgery and receiving an 
interscalene block scheduled for overnight stay that elected to participate in 
another ISB bupivacaine versus LB shoulder study. Patients will be 
approached at the preoperative assessment clinic or surgeon’s clinic at the 
Clinic and Surgery Center if possible by a research staff member to 
determine their interest in participation.  If they decide to be a participant 
they will be consented and given a copy of their consent form for their 
records and a consent will be scanned and placed into EPIC.   These patients 
will have significant time to review the study with research staff as well as 
the physicians performing the procedure due to the fact they arrive several 
hours prior to their scheduled surgery.  All subjects will have enough time to 
ask questions about the study and the potential risks involved regardless of 
which venue they are consented. 
12.2 Identification of Potential Participants: Patients will be identified by 
members of the treatment team in either the surgeon’s clinic, pre-assessment 
clinic, or preoperative area. Patients who have opted out of research will not 
be asked to participate in the study. Patients will be approached to consent 
for the study by a surgeon, anesthesiologist, or member of the research 
team. Patients who agree to participate in the study will sign both a study 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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consent and HIPAA authorization allowing the use of specified information 
contained in medical records for research purposes. 
12.3 Recruitment Materials: n/a 
12.4 Payment: n/a 
13.0 Withdrawal of Participants 
13.1 Withdrawal Circumstances: Subjects who have consented prior to the day of 
surgery and for some reason choose not to participate will be withdrawn and 
a notation will be made in the study records and these people will be 
considered screen failures.  The surgeon may choose to withdraw the patient 
from the study prior to surgery for  any medical reason or if they suffer a 
major life threatening  adverse event. 
13.2 Withdrawal Procedures: If the patient is withdrawn from study prior to the 
procedure, they will be noted in study records as screen failures. If they 
undergo the procedure and they decide they no longer want to be a part of 
the study or withdrawn by the physician, they will be withdrawn and no 
further data will be collected.  This will also be noted in the study 
documentation. 
13.3 Termination Procedures: If the study is terminated for any reason, or there 
is more than 5 % major adverse events the data that is already collected will 
be stored in a secure location only accessible to research personnel on this 
study. No further data will be collected if the study is terminated.  Risks to 
Participants 
13.4 Foreseeable Risks: There is a risk of loss of privacy as well as 
inconvenience the patient as we will ultrasound them prior to and after 
surgery. Otherwise this is a minimal risk study 
13.5 Reproduction Risks: n/a 
13.6 Risks to Others: n/a 
14.0 Potential Benefits to Participants 
14.1 Potential Benefits: There are no potential benefits to the patient from this 
study.  
15.0 Statistical Considerations 
15.1 Data Analysis Plan: We will use the average of the three US exams for each 
timed measurement as the definitive measurement.  We will also use FEV1, 
FVC (or FEV6) and FEV1/FVC (or FEV6) ratio for each time period as a 
secondary measurement. This data will be be given to the statistician who 
will compare those in the LB ISB group to the bupivacaine ISB group to 
evaluate for differences (if any) between the movement of the diaphragms in 
each group.  

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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15.2 Power Analysis: We assumed a 5% rate of block at 24 hours in bupivacaine 
and a 66% block for liposome bupivacaine.  With an alpha of 0.05 and 
power of 80% we determined we need 9 patients in each group.  Assuming 
we would have 20% patients drop out, screen fail, or discharge early we 
planned to enroll 11 per group for total of 22 patients.  
15.3 Statistical Analysis: This study will be analyzed by our staff biostatistician.  
The data will be de-identified and shared with him in box.  The statistician 
will be provided the protocol so they are able to analyze for primary and 
secondary objectives. 
15.4 Data Integrity: All patients will be assigned a unique patient identifier. The 
data that will be sent to the statistician will be de-identified.   
16.0 Confidentiality 
16.1 Data Security: All paper documents and consent forms will be stored in a 
locked cabinet in the anesthesia research office in B573 Mayo. All study 
data will be stored electronically in Box and only the PI and members of the 
research team will have access to the data. 
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
17.1 Data Integrity Monitoring.  
The PI, co-investigators, and research assistants will all have access to the study data 
stored in the University’s Box storage system. All the research assistants have 
experience collecting pain scores and other relevant study information. The PI of 
the study will periodically review the study data to ensure accuracy and 
completeness of study data. 
1.1 
Data Safety Monitoring. The Department of Anesthesiology has 
established a Data and Safety Monitoring Committee consisting of several staff 
anesthesiologists which include persons who are board certified as pain 
specialists. Data will be transmitted in box to persons on the board on a monthly 
basis for review.  If there are patterns of adverse events, the board will meet as 
needed and provide recommendations. 
All safety data will be collected on a case report form and transferred into an 
excel spreadsheet that will be stored in box. Also, all phone call data will be 
collected on a case report form and transferred into excel in box.  
All data will be collected by research assistants on a daily basis.  Subjects are 
monitored at several intervals on day of surgery and daily . 
The data will be reviewed on a regular basis (weekly) by the PI and research 
staff.  If there are consistent complications noted a meeting will be convened by 
the DSMB for recommendations. 
The statistical tests for analyzing the safety data to determine whether harm is 
occurring. 

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VERSION DATE: 3 5/9/2019 
 
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The statistician uses R or SAS for analysis.  Most likely a regression analysis will 
be performed to see which event is most likely the contributor for the 
complications.  Also a chi-square analysis can be performed.  All is very 
dependent on data variability. 
A fatal or serious adverse event that is attributable to either the delivery or the 
study medication itself. 
Provisions to Protect the Privacy Interests of Participants 
Protecting Privacy: Patients will be asked if this is a good time to have the 
ultrasound study. .  All patients will have the right to refuse when contacted.  
Access to Participants: All patients are required to sign a consent that states their 
privacy of the data being collected.  In addition, they are required to sign a 
HIPAA consent that further describes the data being collected.  It also describes 
that all data is de-identified and stored in a secure database.  They will be 
informed that data is stored and reviewed in box which is HIPAA compliant and 
that only study personnel have access.  Patients are part of the PI and co I job at 
the University.   
 
18.0 Compensation for Research-Related Injury 
Compensation for Research-Related Injury: In the event that this research activity 
results in an injury, treatment will be available, including first aid, emergency 
treatment and follow-up care as needed. Care for such injuries will be billed in the 
ordinary manner, to the patient and/or insurance company.  
 
18.1 Contract Language: n/a 
19.0 Consent Process 
19.1 Consent Process (when consent will be obtained):  
Patients will be identified in the pre-operative time period by the block 
anesthesiologist or research team and if possible will be consented by the 
research coordinator or research assistant.   If patients have more questions 
and do not want to sign at their clinic will be asked if it is allowable for a 
study staff member to contact them prior to surgery via phone to clarify if 
they have any questions.  On the day of surgery, if the patient has not 
already signed consent and is still interested in participating in the study 
will be presented with consent and Health and Insurance Portability and 
Accountability Act (HIPAA) forms.  The patient will review the forms with 
the research staff, or anesthesiologist.  Subjects will be reminded that 
participation is completely voluntary, and that they may stop participation 
at any time without question or penalty.  The research staff or 
anesthesiologist will answer any questions that the subjects may have 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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about the study.  If the patient decides to participate, they will be asked to 
sign the consent and HIPAA forms.  One copy will be saved for study 
records, and the subject will be provided with a copy of the forms for their 
own records. Waiver or Alteration of Consent Process (when consent will 
not be obtained):  
Non-English Speaking Participants: n/a. 
19.2 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): 
● 
n/a 
19.3 Cognitively Impaired Adults, or adults with fluctuating or diminished 
capacity to consent: 
● 
n/a 
19.4 Adults Unable to Consent: 
● 
Permission: n/a 
● 
Assent: n/a 
● 
Dissent: n/a  
20.0 Setting 
1.2 Research Sites: Patients will be consented in the surgeon’s clinic or pre 
assessment clinic.  The surgical procedures will take place at the Fairview 
riverside campus.   
20.1 International Research: n/a 
21.0 Multi-Site Research 
● 
n/a 
22.0 Resources Available 
23.0 Resources Available: Research assistants are available to aid in consent and data 
acquisition. All research assistants will be familiar with the study protocol and have 
experience working with similar studies. 
  
We plan to enroll 22 subjects.  The plan is to screen 40 subjects to research this target 
population.  This center performs approximately 500 shoulder procedures 
annually. 
We plan to conduct this study over 3 months.  Enrollment and data collection will be 
completed at this time.  Statistical Analysis will take approximately two months 
to complete. 
 All procedures will be performed in the clinical facilities at the MHealth Clinics and 
Surgery Center and at the West and East Bank. Data storage and analysis will be 
done using desktop equipment which is available at the Research Office B573 
Mayo. 

PROTOCOL TITLE: Evaluation of diaphragm movement after an Interscalene block 
VERSION DATE: 3 5/9/2019 
 
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Revised: 1/19/2018 
23.1 References 
Renes et al. Ultrasound guided low dose interscalene brachial plexus block 
reduces the incidence of hemidiaphragmatic paresis.  Reg Anesth Pain Med. 
2009;34:498-502 
Urmey WF, talts Kh, Sharrock Ne: one hundred percent incidence of 
hemidiaphragmatic paresis associated with interscalene brachial plexus 
anesthesia as diagnosed by ultrasonography. Anesth Analg 1991; 72:498–3