Clinical trial NCT03482973
Conditions: Coronary Artery Disease Sternal Pain
Keywords: Cardiopulmonary Bypass Cardiac Surgery Sternotomy
Sponsor: Beth Israel Deaconess Medical Center
Start date: 2018-06-21; Completion date: 2019-11-27
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether administration of a pecto-intercostal fascial plane block (PIFB) with bupivacaine is a more effective therapy for postoperative analgesia after cardiac surgery as compared to patients who receive a sham block of normal saline.

Detailed description:
The purpose of this study is to determine whether administration of a pecto-intercostal fascial plane block (PIFB) with bupivacaine is a more effective therapy for postoperative analgesia after cardiac surgery as compared to patients who receive a sham block of normal saline.

Specific Aim 1: To determine whether or not a PIFB with bupivacaine can reduce postoperative pain after cardiac surgery. This will be assessed through:

(Aim 1A) opioid consumption in the first 48 hours postoperatively (Aim 1B) patient self-reported pain scores during their hospital stay

Specific Aim 2: To estimate the effect size in order to obtain information that can be used to power future research on the use of regional modalities of analgesia for cardiac surgeries.

Arms: arm 1: 20 cc of 0.25% bupivacaine on each side of the sternum at two time points after surgery and POD1 arm 2: 20 cc of saline on each side of the sternum at two time points after surgery and POD1
Interventions: intervention 1: Bupivacaine Group intervention 2: Placebo
Intervention descriptions: intervention 1: 20cc bupivacaine hydrochloride will be administered on each side at two different time points (immediately post operatively and on day 1). intervention 2: 20cc placebo (0.9% NaCl) will be administered on each side at two different time points (immediately post operatively and on day 1).

Protocol documents:
Prot_SAP_001.pdf: 
(CCI) Committee on Clinical Investigations 
Page 1 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
Pecto-Intercostal Fascial Block for Postoperative Analgesia after 
Cardiac Surgery: A Pilot Study 
Principal Investigator 
Balachundhar Subramaniam, MD MPH 
 
B1. 
PURPOSE OF PROTOCOL 
The purpose of this study is to determine whether administration of a pecto-intercostal fascial plane block (PIFB) 
with bupivacaine is a more effective therapy for postoperative analgesia after cardiac surgery as compared to 
patients who receive a sham block of normal saline.   
 
Specific Aim 1:  We aim to determine whether or not a PIFB with bupivacaine can reduce postoperative pain after 
cardiac surgery.  This will be assessed through:  
(Aim 1A) opioid consumption in the first 48 hours postoperatively 
(Aim 1B) patient self-reported pain scores during their hospital stay 
  
Specific Aim 2:  We aim to estimate the effect size in order to obtain information that can be used to power future 
research on the use of regional modalities of analgesia for cardiac surgeries. 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
Over 80% of the patients undergoing cardiac surgeries experience moderate to severe postoperative pain [1]. Post 
sternotomy pain may lead to a number of complications. Pain elicits a neuro-humoral stress response, increasing 
the sympathetic outflow, which predisposes to cardiac ischemia, arrhythmias, hypercoagulable state in an already 
compromised patient. It also causes pulmonary complications by restricting breathing effort. Other complications 
include postoperative delirium and increased duration of ICU and hospital stay. Thus, pain impairs postoperative 
recovery. So, optimal pain management after cardiac surgery is of paramount importance. Undertreated pain may 
also lead to chronic pain conditions. Around 4% of the cardiac surgical population experience chronic sternal pain 
[2].  
 
Currently, the main modality of postoperative analgesia is by systemic administration of opioids [1]. Opioids are 
given as either patient-controlled analgesia (PCA) or as nurse administered boluses until the patient can be weaned 
off to oral opioids. Other agents used are acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), 
though the use of NSAIDs in cardiac surgical population is controversial, considering the risk of hemorrhagic 
complications [2]. Systemic opioids may lead to a number of adverse events like nausea, vomiting, sedation, 
decreased bowel activity, urinary retention, delirium and life threatening complications like respiratory depression 
[2]. These factors lead to sub-optimal opioid dosing, and also directly prolong duration of ICU and hospital stay. 
 
Regional techniques for analgesia are grossly underused in the cardiac surgical population. Neuraxial techniques 
such as intrathecal, epidural analgesic techniques are disregarded in most centers for the fear of epidural 
hematoma in a patient on anticoagulants [3]. Another concern is the associated sympathectomy and hemodynamic 
instability [4]. Some studies were not able to find a significant benefit of thoracic epidural analgesia on clinical 
outcomes after cardiac surgery [5].  
 
Bilateral paravertebral block is being successfully used in some centers [6]. Many centers use local anesthetic 
infiltration at wound edges and drain sites. This provides analgesia for a limited period and is limited by the duration 
of action of the local anesthetic being used, unless a continuous infusion is being used or repeat blocks are 
administered [1]. 
 
Pain after cardiac surgery is multi-factorial. Apart from direct tissue trauma, inflammatory response to the trauma 
and neural sensitization play an important role in pain [7]. Somatic, musculoskeletal pain results from the skin 
incision, sternotomy, sternal retraction, lower limb venous harvesting, placement of drains and patient positioning. 
The sensory supply associated with skin incision and sternotomy is derived from T2 to T6 segments, and is carried 
by the intercostal nerves [7]. The visceral pain results from incision of the parietal pericardium, which is innervated 
by the phrenic nerve, sympathetic trunks and the vagus [7]. 
 
The intercostal nerves pass between the internal and innermost intercostal muscles for most of their course. 


(CCI) Committee on Clinical Investigations 
Page 2 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
Nearthe sternum, they cross anterior to the internal thoracic vessels and pierce the transversus thoracis muscle, the 
internal and external intercostals, respectively, and the pectoral muscles to become the anterior cutaneous nerves 
supplying the thoracic wall.  A single shot injection of local anesthetic in the plane between pectoralis major muscle 
and the external intercostal can effectively block the anterior thoracic cutaneous nerves. This is called the pecto-
intercostal fascial block (PIFB) [8-10].  PIFB has been studied for analgesia after breast surgeries and also in 
thoracic trauma [8]. It is a promising option considering its efficacy and ease of administration.  
 
PIFB might prove to be a useful analgesic technique, devoid of the systemic adverse events associated with opioids 
and the neuraxial and hemodynamic complications associated with neuraxial techniques. It is a relatively superficial 
plane block therefore it is very safe. It could prove useful in the acute setting of postoperative pain and even go a 
long way preventing chronic pain.  
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
Study Design 
This is as a prospective, randomized, placebo controlled double-blinded trial of patients undergoing cardiac surgery 
at BIDMC.  Patients meeting inclusion criteria with no exclusions will be approached to obtain written informed 
consent.  Patients who decide to participate will receive a PIFB with either bupivacaine hydrochloride or placebo. 
Data will be collected in order to determine whether there is a difference in opioid consumption or pain scores 
following surgery.    
 
Enrollment 
Study subjects will be identified from the perioperative information management system (PIMS), surgical consult 
lists, cardiac surgical clinic visit schedules and pre-admission testing (PAT) clinic visit schedules. After confirming 
eligibility, the patient will be approached by a research team member to discuss the study in detail. Written informed 
consent will be obtained before initiation of any study procedures. 
 
Randomization 
Enrolled subjects will be randomized to one of the two study groups, in a 1:1 randomization ratio (Please see the 
table below). Patients randomized to Group 1, or the bupivacaine group, will receive 20cc of bupivacaine 
hydrochloride on each side (40ccs total at each time point). In Group 2, patients will receive 20cc of normal saline 
on each side. Use of placebo is a standard control procedure in clinical trials and will allow for the assessment of 
unbiased quantitative data on the efficacy across all treatment groups. 
 
 
Study Drug (per side) 
Group 1 
20cc bupivacaine hydrochloride on each side 
Group 2 
20cc placebo (0.9% NaCl) on each side 
 
Administration of the Study Medications 
Trained anesthesiologists will use ultrasound guidance to administer the PIFB in the plane between the external 
intercostal and the pectoralis major muscles. The block will be given as an injection on both sides of the chest at the 
following periods:  
 
Time Point 
Administration Protocol  
Immediate Postoperative Period 
The study drug/placebo will be given within two hours of the patient 
entering the ICU.   A total of 40ccs (20cc on left, 20cc on right) will be 
administered at this time point.   
Postoperative Day 1 
The study drug/placebo will be given between 9 and 11 am.   A total 
of 40ccs (20cc on left, 20cc on right) will be administered at this time 
point.   
 
The patient, anesthesia provider administering the block, nurses assessing pain and the study team members will 


(CCI) Committee on Clinical Investigations 
Page 3 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
all be blinded for the group.   In case of an emergency the randomization can be obtained from the research 
pharmacy.   
 
Standard Therapy (Usual Care) 
All preoperative care and intraoperative management will follow the current standard of care in all study 
participants. The current standard analgesic therapy in the post-cardiac surgical patients comprises of nurse 
administered boluses of IV opioids (intravenous morphine or hydromorphone or fentanyl) or oral opioids such as 
oxycodone titrated to pain relief.   All patients will receive bolus doses of IV opioids (morphine/fentanyl/ 
hydromorphone) or oral opioids (oxycodone) as needed for breakthrough pain, as is the standard of care.   
 
Data Collection, Outcomes and their Measurement 
Patient comorbid conditions, surgery and anesthetic drugs used will be obtained from the patient’s medical record, 
the Society of Thoracic Surgery database and the Anesthesia Information Management System. Data related to 
primary and secondary outcomes such as pain scores, opioid doses, duration of stay and complications will be 
obtained from the medical records.  
 
Pain is routinely assessed in the postoperative period by nurses on an 11 point scale (i.e. patients are asked to rate 
their pain on a scale of 0 to 10). This is typically assessed every 4-8 hours by nursing staff and is readily available 
on the patient’s electronic medical records.  
 
The total dose of opioids consumed in the 48 hours post-operative period will be obtained from the patient’s medical 
records. This will be converted to morphine equivalents for standardization of the outcome and for ease of analysis. 
 
Daily 3D CAM assessment will also be performed on the study subjects in order to assess whether or not they are 
delirious. This assessment takes approximately 5 minutes to complete. If daily assessments are negative for 3 
consecutive days (i.e. days 5, 6 & 7), they will then be completed every other day until date of discharge. In 
addition, these assessments will be done at the patient’s convenience to ensure ability to finish the evaluations. 
 
Data will be collected and stored in REDCap or on password protected computers.  Any data collected on paper will 
be stored in locked study offices or file cabinets.   
 
Adverse Event Reporting 
Our patient population is by definition undergoing high risk surgery and is therefore critically ill.  It is expected that 
they will have a number of unrelated adverse health events during the course of their hospital stay.  Therefore, we 
will limit the scope of our AE monitoring and reporting to the following: 
 
 
All Serious Adverse Events, including unexpected death, believed to be related to the study   
 
 
Unexpected, Non-serious Adverse Events believed to be possibly or probably related to the intervention, 
including the pre-specified list below: 
 
infection 
 
hematoma 
 
local anesthetic systemic toxicity  
 
 
Evidence for adverse events will be assessed daily during the hospital stay, for a maximum of four postoperative 
days, which well exceeds the half-life of the study drugs.  
 
 
B. 
Statistical Considerations 
Sample Size Justification: In this study and we are looking at the effect of a sternal block on cardiac surgery 
patients’ opioid consumption in the first 48 hours postoperatively (primary outcome).  Based on historical data of 
analgesic use from patients at BIDMC, the average use of morphine per day is approximately 12 mg, or 24mg in 
48 hours.  Using a two-sided alpha of 0.05, power of 80%, expecting a 50% reduction in opioid use and standard 
deviation of 18 mg, we would need 36 patients per group in order to detect a difference.  As it is possible that 
some patients may withdraw prior to administration of the study drug, we will aim to enroll 80 patients (40 per 
group) to account for this potential drop out.  Data from study will be used to adequately power a larger trial, 
based on the treatment effect seen in this study.    


(CCI) Committee on Clinical Investigations 
Page 4 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
 
Data Analysis: Analyses will be conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC) or later.  
Descriptive statistics of the data will be performed. Continuous data (age, pain scores, and opioid consumption) 
will be represented using mean (± standard deviation) or median (interquartile range) for variables not normally 
distributed and compared using parametric or non-parametric t-tests as appropriate.  Categorical data such as 
the proportion of patients who successfully completed the study protocol will be presented as frequencies or 
proportions and analyzed using a chi-square or Fishers Exact test. Linear and logistic regression will be employed 
as necessary to adjust for potential differences between groups that persist after randomization.  All two sided p-
values < 0.05 will be considered statistically significant.   
 
 
The primary outcome of the study, opioid consumption in the first 48 hours postoperatively, will be assessed by 
review of the medical record.  Other secondary outcomes include: 
 
Pain scores 
 
ICU length of stay 
 
Hospital length of stay 
 
Incidence of complications (including infection, hematoma, local anesthetic systemic toxicity directly related 
to the block or the drug used in the block) 
 
Incidence of delirium throughout the post-operative period  
 
Electronic data will be stored on password-protected computers behind the BIDMC firewall or in REDCap directly.  
Data will be analyzed by a statistician at BIDMC.      
 
C. 
Subject Selection 
Inclusion Criteria 
 
Patients 18 years of age or older 
 
Undergoing cardiac surgery with sternotomy, limited to CABG, CABG+valve surgeries and isolated valve 
surgeries. 
 
 
Exclusion Criteria 
 
Current participation in another interventional study 
 
Preoperative LVEF < 30% 
 
Use of mechanical circulatory support 
 
Emergent procedures 
 
Aortic surgeries, transplants ventricular assist device insertions, bentall, or grafts 
 
Minimally invasive cardiac procedures or those with thoracotomy approach 
 
Patients receiving other modalities of regional anesthesia like intrathecal morphine 
 
Chronic opioid use for chronic pain conditions with tolerance (total daily dose of an opioid at or more than 
30 mg morphine equivalent for more than one month within the past year) 
 
Current use of TCA, gabapentin, or pregabalin  
 
Hypersensitivity to bupivacaine 
 
Women who are pregnant or breastfeeding 
 
Non English speaking 
 
Drop-out Criteria 
Prior to initiation of any study medications, the following criteria will be assessed.  If the patient meets any of the 
following they will be excluded from the study.   
 
Unable to meet the standard Fast Track Criteria postoperatively, as determined by the surgical and ICU 
Physician Assistants 
 
Hemodynamically unstable (defined as HR > 120, SBP < 80, MAP < 50 within 30 minutes prior to drug 
administration) 
 
Abnormal chest tube output (1000cc in 2 hours) 
 
Oxygenation outside of normal limits (defined as PaO2 < 60mmHg on an FiO2 of 1.0 or SpO2 < 85% within 
30 minutes prior to drug administration)  
 
Received an infusion or bolus ≥ 0.05 mcg/kg/min of epinephrine 
 
Received an infusion or bolus ≥ 0.50 mcg/kg/min of milrinone 
 
Received an infusion or bolus ≥ 0.20 mcg/kg/min of norepinephrine 


(CCI) Committee on Clinical Investigations 
Page 5 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
 
Significant clinician or nursing concern 
 
We will enroll patients without regard to gender, race, or ethnic distribution.   
  
B4. 
POSSIBLE BENEFITS 
There are no guaranteed health benefits to the patient being included in this study.  An improved understanding, 
and potentially information as to whether or not this medication can provide symptom relief, may improve comfort 
after cardiac surgery for other patients in the future.     
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
Risk of Bupivacaine 
Bupivacaine is an FDA approved medication for the current indication. Cardiotoxicity, which includes arrhythmias, 
hypotension, bradycardia and cardiac arrest, is less common when the doses used do not exceed toxic limits. In 
the intensively monitored setting of cardiac ICU, any signs of impending cardiotoxicity can be identified early and 
managed effectively. Bupivacaine systemic toxicity can also manifest as seizures, which is less common in the 
doses used in the study.  Further, other central nervous system reactions include restlessness, anxiety, dizziness, 
tinnitus, blurred vision, or tremors.  Despite this, bupivacaine is effectively used in regional anesthetic techniques 
and the advantages of effective analgesia in terms of better patient recovery seem to outweigh the risks. 
 
Risks Associated with Block Administration 
PIFB is a relatively superficial block and is devoid of complications like pneumothorax, especially when performed 
under ultrasound guidance. Infection secondary to the invasive procedure is rare because of the sterile aseptic 
precautions used to administer the block. There is a minor risk of hematoma associated with any regional block 
but the pecto-intercostal fascial plane is a relatively avascular plane and the use of ultrasound guided visualization 
further reduces the risk of hematoma. 
 
Risk of a Confidentiality Breach 
Any patient participating in a research study runs a small risk of breach of confidentiality.  All study staff for this trial 
are well trained in HIPAA regulations and BIDMC confidentiality standards.  Patient data will stored in locked 
cabinets and will be password protected computers on BIDMC network secure servers or in REDCap directly. 
 
Risk/Benefit Ratio 
The local anesthetic used in this study is approved by FDA for regional analgesia.  When administered at 
recommended safe dosages and when monitored in the intensive care setting, the risks of local anesthesia 
systemic toxicity associated with bupivacaine are far too small compared to the benefits of decreased pain and 
enhanced recovery following cardiac surgery.   
 
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
Recruitment 
Prescreening will be accomplished by reviewing the operating room schedule and surgical consult lists. Patient 
medical records will be reviewed for inclusion and exclusion criteria.  All patients who meet inclusion criteria with 
no exclusions will be approached in the cardiac catheterization holding area, PAT clinic, cardiac surgery clinic, or 
in the preoperative holding area for full written informed consent.   
 
Consent 
Written informed consent will be obtained prior to the scheduled surgery in a private, secure location. Consent will 
be obtained by one of the approved study team members. At the time of consent, all study procedures will be 
explained in detail, including the associated risks and benefits.  The subjects will have the opportunity to ask any 
and all questions, and will be reminded that participation is voluntarily.  All subjects will be consented with curtains 
drawn or the door closed, assuring patient privacy.  Written informed consent will then be obtained prior to surgery 
and initiation of any research procedures.  If a physician investigator is not available to meet with the proxy in 
person to obtain written consent, he/she will be available by phone for any questions.  Another member of the 
study team, as approved by the CCI, will obtain consent on-site.  This will be documented in a consenting memo. 
 
The research staff undergoes a rigorous consent training process. Within the Center for Anesthesia Research 
Excellence (CARE) at BIDMC, this training includes: didactic sessions, mandated attendance at CCI/HSPO 
seminars related to the informed consent process, shadowing of informed consent in a variety of contexts, trainee-


(CCI) Committee on Clinical Investigations 
Page 6 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
led informed consent conversations with the aid of consenting checklists and accompanied by senior staff member 
and/or PI, robust feedback sessions, and clear communication when the team member is skilled enough to 
engage in informed consent discussions without direct supervision.  
 
Subject Protection 
It is unlikely that patients will be vulnerable to coercion or undue influence in this study. Patients will be informed 
that their decision to participate or not to participate will in no way affect their relationship with their health care 
provider. Patients have the ability to discontinue their participation at any time.   
 
B7. 
STUDY LOCATION 
Privacy  
All efforts will be taken to ensure patient privacy. Patient interactions including consent will take place in private 
clinical settings with curtains/doors closed so as to provide privacy and comfort. Throughout the study, only the 
minimum required information will be collected, assuring patient privacy during the study protocol as with usual 
patient care. Data collection from chart extraction will occur only on password-protected computers secured by 
the BIDMC firewall or in REDCap directly. Data collected will be limited to only the minimum necessary to 
accomplish the stated research purposes. 
 
Physical Setting 
All patients will be enrolled at BIDMC.  Consent will be obtained from eligible participants in the cardiac 
catheterization lab holding area, PAT clinic, cardiac surgery clinic, or in the preoperative holding area.  Study 
procedures, including administration of the PIFB will be performed in the operating room, the subject’s inpatient 
room in the intensive care units, or in the ward at BIDMC. Data will be abstracted from the patients’ chart and 
will be stored on password-protected computers behind the BIDMC firewall or in REDCap directly. All data 
collected on paper will be maintained in locked study offices accessible to only the study team.   
 
B8. 
DATA SECURITY 
Data will be stored on password-protected computers behind the BIDMC firewall and entered into a computer 
database (REDCap). Computers and data collected on paper will be stored in locked rooms. For all analyses 
subjects will be identified only by their unique coded study ID number assigned for the sole purpose of this 
project.  Limited information will be retained on patients who are prescreened and do not qualify, or who are 
approached and declined, for the purposes of generating a CONSORT diagram for the trial.   
 
B9 
Multi-Site Studies 
 
N/A – Single Center Study 
 
Is the BIDMC the coordinating site?       
 Yes    
 No  
 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No  
 
B10 
Dissemination of Research Results 
Patients will be thanked for their time throughout the study. Because study results are likely to be published a 
few years after a given subject’s participation, study investigators are concerned that mailing the published 
manuscript and an additional thank-you note years after participation risks violating subject privacy, as mailing 
addresses are increasingly likely to change with passing time. It is out of the scope of this study to continue 
tracking mailing addresses after study completion.    
 
B11 
References 
1. Huang, A.P.S. and R.K. Sakata, Pain after sternotomy – review. Brazilian Journal of Anesthesiology (English 
Edition), 2016. 66(4): p. 395-401. 
2. Bigeleisen, P.E. and N. Goehner, Novel approaches in pain management in cardiac surgery. Current Opinion 
in Anaesthesiology, 2015. 28(1): p. 89-94. 
3. Ziyaeifard, M., R. Azarfarin, and S.E. Golzari, A Review of Current Analgesic Techniques in Cardiac Surgery. 
Is Epidural Worth it? Journal of cardiovascular and thoracic research, 2014. 6(3): p. 133-40. 
4. Kowalewski, R., et al., Neuraxial anesthesia for cardiac surgery: thoracic epidural and high spinal anesthesia 
- why is it different? HSR proceedings in intensive care & cardiovascular anesthesia, 2011. 3(1): p. 25-28. 


(CCI) Committee on Clinical Investigations 
Page 7 of 7 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date:  04/09/2019 
 
5. Svircevic, V., et al., Thoracic Epidural Anesthesia for Cardiac Surgery: A Randomized Trial. Anesthesiology, 
2011. 114(2): p. 262-270. 
6. Harle, C.C. and S. Ganapathy, Paravertebral analgesia for cardiac surgery. Techniques in Regional 
Anesthesia and Pain Management, 2008. 12(1): p. 57-63. 
7. Mazzeffi, M., et al., Poststernotomy pain: a clinical review. Journal of cardiothoracic and vascular anesthesia, 
2011. 25(6): p. 1163-78. 
8. Hong, B., et al., Thoracic interfascial nerve block for breast surgery in a pregnant woman: a case report. 
Korean J Anesthesiol, 2017. 70(2): p. 209-12. 
9. de la Torre, P.A., et al., A novel ultrasound-guided block: a promising alternative for breast analgesia, in 
Aesthet Surg J. 2014: England. p. 198-200. 
10. López-Matamala, B., et al., A new thoracic interfascial plane block as anesthesia for difficult weaning due to 
ribcage pain in critically ill patients. Medicina Intensiva, 2017. 38(7): p. 463-465. 
 

ICF_000.pdf: 
[CCI] Committee on Clinical Investigations 
 
Page 1 of 10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date: 07/09/2018 
 
**FOR CCI USE ONLY** 
Approved by the Beth Israel Deaconess Medical Center  
Committee on Clinical Investigations:  
 
Consent Approval Date:   
01/28/2019 
 
 
Protocol Number:  
2018P000044   
 
 
 
INFORMED CONSENT FORM TO TAKE PART IN A RESEARCH STUDY 
 
SUBJECT’S NAME:    
TITLE OF RESEARCH PROTOCOL:  Pecto-Intercostal Fascial Block for Postoperative Analgesia after 
Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR:  Balachundhar Subramaniam, MD MPH 
PROTOCOL NUMBER:   2018P000044 
 
INTRODUCTION: 
 This is a research study; 
 Your participation is voluntary; 
 A research study includes only people who choose to take part; 
 You may or may not benefit from participating in the study.  However, your participation 
may help others in the future as a result of knowledge gained from the research; 
 You may leave the study at any time; 
 If you choose not to take part, or if you leave the study, your decision will in no way harm 
your relationship with any member of the research team or any other individuals at Beth 
Israel Deaconess Medical Center. 
 
Please read this consent form carefully and ask the investigators or study staff to explain any words 
orinformation that you do not clearly understand.  Once you read this consent form and understand 
what your participation in this study will involve, you will be asked to sign this form if you wish to take 
part.  You will be given a signed copy of the form to keep for your records. 
 
DISCLOSURE OF SPECIAL INTERESTS OF BIDMC AND INVESTIGATORS 
This study is being conducted by Balachundhar Subramaniam, MD MPH. There is no external funding 
agency in this study. Neither BIDMC nor Dr. Subramaniam has any additional interests in this research 
project. 
 
WHOM TO CONTACT IF YOU HAVE QUESTIONS OR PROBLEMS 
If you have any questions, concerns or complaints about this research or experience any problems, 
you should contact Dr. Balachundhar Subramaniam at [617] 754-2712. 
 
PURPOSE 
Cardiac (heart) surgery is a procedure associated with moderate to severe pain after surgery. A big 
contributor to the overall pain is sternal pain, or pain on the chest at the site of the surgical incision. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 2 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
Currently, pain after surgery is treated by pain-reducing medications called opioids that you receive 
through a vein in your arm.  Administration of opioids may lead to a number of adverse events like 
nausea, vomiting, sedation, decreased bowel activity, and more severe complications such as issues 
with your lungs and breathing.   
 
A regional analgesic block (an injection of pain medicine between the shoulder and rib muscles) has 
been shown to reduce pain after breast or chest trauma surgeries.  The anesthetic bupivacaine (study 
medication) has been Food and Drug Administration (FDA) approved for blocks and is widely used.  
The efficacy of using an analgesic block to reduce pain and opioid use after cardiac surgery has not 
been studied in enough people yet.   
 
In this study we want to determine whether use of a regional analgesic block with bupivacaine can 
help reduce the chest pain you may experience following heart surgery.  
 
STUDY PARTICIPANTS 
You have been asked to be in the study because you are undergoing heart surgery. Approximately 80 
patients will participate in this study at Beth Israel Deaconess Medical Center. 
 
DESCRIPTION OF STUDY DETAILS 
If you agree to be in this study, you will be asked to read and sign this consent form.  After you sign the 
consent form, the following things will happen: 
 
1. Screening Procedures:  Screening procedures are tests and procedures that will be done to 
determine if you are eligible to take part in the research study.  For this research study, the 
screening procedures include:   
 
We will review of your medical records to ensure that you are appropriate to participate in the 
study and that you don’t not have any sensitivities to the study medication.  
 
2. Randomization Procedures:  It is not clear at this time whether the medication used in this 
study would affect your pain after cardiac surgery.  For this reason, the treatment plan 
offered to you will be picked by chance [like the flip of a coin].  You will not be able to choose 
which treatment you receive.  The chances of receiving either of the treatments are 
approximately equal. After the randomization, you will be assigned to one of the following 
groups: 
 
 
Group 1: Bupivacaine  
 
 
 
Group 2: Placebo (Salt water) 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 3 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
Depending upon the group to which you are assigned, you may receive a placebo instead of 
the study medication.  A placebo is an inactive saline solution that looks like the study drug, 
but a placebo contains no active medication.  Placebos are used to help determine if the 
results of the study are truly from the study drug.  Neither you nor your physician will know 
whether you will be receiving the study drug or the placebo.  However this information can be 
learned in case of an emergency. 
 
It is important to note that this study medication will be given in addition to the regular pain 
medications you might receive after cardiac surgery.     
 
3. Research Procedures:  If you qualify to take part in this research study, you will undergo 
these research procedures:  
 
A) Administration of the Study Medication: As part of your participation, we will be 
administering the study medication at two different time periods: 1) shortly after your 
surgery when you are first in the intensive care unit, and 2) one day after your surgery. 
The study medication or placebo will be administered by a trained anesthesiologist.   
 
At each time point you will be given a total of 20 cc or about two tablespoons of study 
medication injection on each side of your sternum (chest). Ultrasound will be used to 
guide the injection and confirm it is in the appropriate place between the shoulder and 
rib muscles.   
 
B) Short Daily assessment: We will ask you a few thinking and memory questions each 
day while you are in the hospital. This will take about 3-5 minutes.  
 
C) Data Collection from your Medical Record: We will be accessing your medical 
records in order to obtain information on how you are doing. Specifically we will be 
looking at the pain medications administered and your reported pain scores.   This 
data is routinely collected by nurses as part of your stay in the hospital after surgery.   
 
Other aspects of your surgery and care after surgery will occur as they normally would 
if you had decided not to participate in the study.   
 
4. Monitoring/Follow-Up Procedures.  Procedures performed to evaluate the effectiveness and 
safety of the research procedures are called “monitoring” or “follow-up” procedures.  For this 
research study, the monitoring/follow-up procedures include: 
 
We will monitor you for four days after surgery to see how you are doing. To do this we will 
review your medical records and speak with your doctors and nurses as necessary.  
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 4 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
 
RISKS AND DISCOMFORTS 
As a result of your participation in this study, you are at risk for side effects listed in this section.  
You should discuss these with the investigator and with your regular doctor if you choose.   
 
Ultrasound is a very safe technology, and has no additional risks associated with it.  The risks of 
bupivacaine include: 
 
More Common [>5% occurrence] 
 Constipation, nausea, vomiting 
 
Less Common [>1% but <5% occurrence] 
 Abnormal nervous system function such as excitation, depression, numbness, tingling 
sensation, seizures, drowsiness, unconsciousness. 
 Abnormal heart functions including abnormal rhythm, decreased heart rate, decreased 
blood pressure, or heart block  
 
Rare [<1% occurrence] 
 Allergic reactions including hives, itching, redness, swelling, coughing, sneezing and 
breathing difficulty 
 Persistent numbness, tingling and weakness at the site of administration 
 
There is also a minor risk of hematoma (a bruise or collection of blood under the skin) associated 
with the administration of any block; however use of ultrasound to guide administration of the block 
lessens the possibility of this risk.   
 
LOSS OF CONFIDENTIALITY 
There is the potential for loss of confidentiality by participating in this study.  Every effort will be 
made to protect the confidentiality of your identifiable information.   
 
CONFIDENTIALITY 
Information learned from your participation in this study and from your medical record may be 
reviewed and photocopied by the Food and Drug Administration (FDA) and/or other federal and 
state regulatory agencies, and the Committee on Clinical Investigations, the Human Subjects 
Protection Office and others involved in research administration of the Beth Israel Deaconess 
Medical Center with protection of confidentiality so far as permitted by applicable law.  Information 
resulting from this study and from your medical record may be used for research purposes and may 
be published; however, you will not be identified by name in such publications. 
 
POSSIBLE BENEFITS 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 5 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
It is not possible to predict whether you will benefit directly from participation in this study.  However, 
your participation may help others in the future as a result of knowledge gained from the research. 
 
OTHER AVAILABLE OPTIONS 
Taking part in this study is voluntary. Instead of being in this study, you can decide not to participate.  
 
This research study is not meant to diagnose or treat medical problems. Participation in this 
research study does not take the place of routine physical examinations or visits to your regular 
doctor. 
 
We recommend that you discuss these and other options with the investigator and your regular 
doctor so that you can make a well-informed decision about participating in this study. 
 
IF YOU DECIDE NOT TO TAKE PART IN THE STUDY 
Participation in this study is voluntary.  You have the right to decide not to take part in this study.  If 
you choose to participate, you have the right to leave the study at any time. Your decision to not 
participate will not result in any penalties or loss of benefits to you. The investigators will tell you 
about new information that may affect your willingness to stay in this study.  
 
If you decide not to participate in the study or decide to leave the study early, your decision will not 
affect your relationship with the research team or any other individual at Beth Israel Deaconess 
Medical Center.   
 
INVESTIGATORS RIGHT TO STOP THE STUDY 
The investigators have the right to end your participation in this study if they determine that you no 
longer qualify to take part, or if it would be dangerous for you to continue, or if you do not follow 
study procedures as directed by the investigators. Beth Israel Deaconess Medical Center or the 
funding source may stop the study at any time. 
 
COSTS AND/OR PAYMENTS TO YOU 
 
COSTS COVERED BY STUDY 
You will not be charged for the drug Bupivacaine Hydrochloride, which is part of this research study. 
However, you and your insurance company will be charged for other tests, procedures or 
medications of this study that are considered standard treatment for your medical condition.  
 
CO-PAYMENT/DEDUCTIBLE STATEMENT 
You will be responsible for any co-payments or deductibles that are standard for your insurance 
coverage.   
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 6 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
PAYMENTS TO YOU: 
You will not be paid for your participation in this study.   
 
COST OF RESEARCH RELATED INJURY: 
If you are injured as a direct result of your participation in this study you should contact the 
Investigator at the number provided under the section “Whom to Call if You Have Questions” in this 
form.  You will be offered the necessary care to treat your injury.  You or your insurance company 
will be billed for medical care and/or hospitalization related to this injury.  You will be responsible for 
all co-payments and deductibles required under your insurance.  BIDMC will consider 
reimbursement of injury related expenses not covered by your insurance on a case-by-case basis.  
At this time there is no plan to reimburse you for items such as lost wages or lost time from work.  
By signing this consent form you have not given up any legal rights. 
 
OTHER IMPORTANT INFORMATION 
A description of this clinical trial will be available on www.ClinicalTrials.gov as required by U.S. law.  
This Web site will not include information that can identify you.  At most, the Web site will include a 
summary of the results.  You can search this Web site at any time. 
  
AUTHORIZATION FOR USE AND DISCLOSURE OF YOUR PROTECTED HEALTH 
INFORMATION 
As part of this study, we will be collecting, using and sharing with others information about you.  
Please review this section carefully as it contains information about the federal privacy rules and the 
use and disclosure of your information.   
 
PROTECTED HEALTH INFORMATION [PHI] 
By signing this informed consent document, you are allowing the investigators and other authorized 
personnel to use [internally at BIDMC] and disclose [to people and organizations outside the BIDMC 
workforce identified in this consent] health information about you.  This may include information 
about you that already exists (for example: your medical records and other sources of health 
information, demographic information, the results of any laboratory tests, and mental health records 
(if applicable) as well as any new information generated as part of this study.  This is your Protected 
Health Information. 
 
PEOPLE/GROUPS AT BIDMC WHO WILL SHARE AND USE YOUR PROTECTED HEALTH INFORMATION 
Your Protected Health Information may be shared with and used by investigators working on this 
study, including the supporting research team (such as research assistants and coordinators, 
statisticians, data managers, laboratory personnel, pharmacy personnel, and administrative 
assistants), and may also be shared and used by other health care providers at BIDMC who have 
treated you in the past and have information relevant to the research, or who provide services to you 
in connection with the research.  Your Protected Health Information may also be shared with the 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 7 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
members and staff of the Committee on Clinical Investigations of Beth Israel Deaconess Medical 
Center, which is responsible for reviewing studies for the protection of the research subjects.  
 
PEOPLE/GROUPS OUTSIDE OF BIDMC WITH WHOM YOUR PROTECTED HEALTH INFORMATION WILL BE 
SHARED 
We will take care to maintain confidentiality and privacy about you and your Protected Health 
Information.  We may share your Protected Health Information with the following groups so that they 
may carry out their duties related to this study: 
 
 Statisticians and other data monitors not affiliated with BIDMC 
 Your health insurance company 
 The Food and Drug Administration [FDA], the Department of Health and Human Services 
[DHHS], the National Institute of Health [NIH], the Office for Human Research Protections 
[OHRP], and other federal and state agencies that may have jurisdiction over the research 
 Hospital and Clinical Research Accrediting Agencies 
 
Those who receive your Protected Health Information during the course of the research may not be 
required by the federal privacy regulations to protect it, and they may make further disclosures to 
others and use your information without being subject to penalties under those laws.   
 
WHY WE ARE USING AND SHARING YOUR PROTECTED HEALTH INFORMATION 
The main reason for using and sharing your Protected Health Information is to conduct and oversee 
the research as described in this Informed Consent Document.  There are many other reasons 
beyond the research for which BIDMC may use or disclose your Protected Health Information.  Not 
all of these reasons require your express written authorization.  For example, we will use and share 
your Protected Health Information to ensure that the research meets legal, institutional and 
accreditation requirements and to conduct public health activities.  The various ways in which 
BIDMC may use and disclose your protected health information without your authorization are 
explained in a document called the Notice of Privacy Practices.  If you have not received a copy of 
BIDMC’s Notice of Privacy Practices, please ask us for one and review it before signing this form.  In 
addition to signing this document, you may also be asked to sign a BIDMC General Agreement form 
acknowledging that you have received the BIDMC Notice of Privacy Practices.   
 
NO EXPIRATION DATE – RIGHT TO WITHDRAW AUTHORIZATION 
Your authorization for the use and disclosure of your Protected Health Information in this Study shall 
never expire.  However, you may withdraw your authorization for the use and disclosure of your 
Protected Health Information at any time provided you notify the Principal Investigator in writing.  If 
you would like to take back your authorization so that your Protected Health Information can no 
longer be used in this study, please send a letter notifying the Principal Investigator of your 
withdrawal of your authorization to Dr. Balachundhar Subramaniam at 330 Brookline Ave., Boston, 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 8 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
MA  02215. Please be aware that the investigators in this study will not be required to destroy or 
retrieve any of your Protected Health Information that has already been used or disclosed before the 
Principal Investigator receives your letter, and they are permitted to continue to use and disclose 
your previously collected information as necessary to complete the research. 
 
REFUSAL TO SIGN 
Your clinical treatment may not be conditioned upon whether you sign the Authorization for 
Research. However, if you choose not to sign this informed consent document and authorization for 
the use and disclosure of your Protected Health Information, you will not be allowed to take part in 
the research study. 
 
RIGHT TO ACCESS AND COPY YOUR PHI 
If you wish to review or copy your Protected Health Information as it is made part of your medical 
record, you may do so after the completion or termination of the study by sending a letter to the 
Principal Investigator requesting a copy of your Protected Health Information.  You may not be 
allowed to inspect or copy your Protected Health Information until this study is completed or 
terminated. 
 
ADDITIONAL CONTACT FOR QUESTIONS OR CONCERNS 
You may contact the Human Subjects Protection Office at [617] 975-8500 in the event that you 
would like to obtain information or to offer input about the research study.   This office is 
independent of the investigator or investigator’s research staff and can also assist with questions 
relating to your rights as a participant in research, which may include questions, concerns or 
complaints about your participation in the study. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 9 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
THE FOLLOWING PARAGRAPHS CONTAIN SOME STANDARD INFORMATION WHICH 
GENERALLY APPLIES TO INDIVIDUALS PARTICIPATING IN A RESEARCH STUDY. 
 
CONSENT FORM FOR CLINICAL RESEARCH 
I have read the previous page[s] of the consent form and the investigator has explained the details of the 
study.  I understand that I am free to ask additional questions. 
 
If I wish additional information regarding this research and my rights as a research subject, or if I believe I 
have been harmed by this study, I may contact the Human Subjects Protection Office (HSPO). 
 
I am aware that this is a research project and that unforeseen side effects may occur. 
 
I understand that the Beth Israel Deaconess Medical Center has no formal program for compensating 
patients for medical injuries arising from this research.  Medical treatment will be provided for injuries at the 
usual charge to me or to my insurer unless payment is otherwise provided for in this consent form. 
 
I understand that participation in this study is voluntary and I may refuse to participate or may discontinue 
participation at any time without penalty, loss of benefits, or prejudice to the quality of care which I will 
receive. 
 
I acknowledge that no guarantees have been made to me regarding the results of the treatment involved in 
this study, and I consent to participate in the study and have been given a copy of this form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Subject or 
 
 
 
 
Date 
Legally Authorized Representative   
(Parent if the subject is a minor) 
 
 
 
 
 
 
 
 
 
 
 
 
Relationship of Legally Authorized Representative to Subject   
 
 
The subject has been given the opportunity to read this consent form and to ask questions before signing, and 
has been given a copy. 
 
___________________________________________________________ 
SIGNATURE OF INVESTIGATOR/Co-Investigator   
DATE 
 
__________________________________________________________ 
PRINT INVESTIGATOR’S/Co-Investigator’s  
NAME 
A signing co-investigator must be listed on the study’s approved Research Staffing Form at the time of consent. 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020


[CCI] Committee on Clinical Investigations 
Page 10 of 10 
 
SUBJECT'S NAME: 
TITLE OF RESEARCH PROTOCOL: Pecto-Intercostal Fascial Block for 
Postoperative Analgesia after Cardiac Surgery: A Pilot Study 
PRINCIPAL INVESTIGATOR'S NAME: Balachundhar Subramaniam, MD 
MPH 
PROTOCOL #: 2018P000044 
 
Informed Consent – Part D 
CCI Form: 6-2017 
PI Revision Date:   07/09/2018 
 
THE FOLLOWING SECTIONS ARE NOT NEEDED FOR ALL STUDIES AND SHOULD BE 
UTILIZED AS INDICATED: 
 
If the subject is able to speak and understand English but is not able to read or write  
 
I was present during the entire oral presentation of the informed consent and witnessed the subject’s agreement to 
participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
If the subject is able to understand English but is not physically able to read or write or see 
 
I was present during the entire oral presentation of the informed consent and witnessed the subject’s agreement to 
participate in the study. 
 
Signature of Witness:  
 
Printed Name of Witness:  
 
Date:   
 
 
 
If the subject is not English speaking and signed the translated Short Form in lieu of the English consent 
document. 
As someone who understands both English and the language spoken by the subject, I interpreted, in the subject’s 
language, the researcher’s presentation of the English consent form.  The subject was given the opportunity to ask 
questions.  
Signature of Interpreter:  
 
Printed name of Interpreter:  
 
Date:  
 
 
 
COMMITTEE ON CLINICAL INVESTIGATIONS 
APPROVAL EXPIRATION DATE 
 
01/27/2020