Regional Blockade of the Sternum With Liposomal Bupivacaine Prior to Incision Decreases Opioid Use in Patients Undergoing Cardiac Surgery (Sternal Block)
Phase: PHASE4
Conditions: Cardiovascular Surgery, Pain, Postoperative, Block
Sponsor: Baylor Research Institute

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Title: Regional Blockade of the Sternum with Liposomal Bupivacaine Prior to Incision 
Decreases Opioid Use in Patients undergoing Cardiac Surgery 
 
Personnel: 
 
a) Principal Investigator: Katherine B. Harrington, MD 
b) Sub-Investigators:  
i) 
James Wheeless, MD 
ii) William Hoffman, MD 
iii) William Ryan, MD 
iv) William Brinkman, MD 
v) J. Michael DiMaio, MD 
vi) Timothy George, MD 
vii) David Moore, MD 
viii) Kelley Hutcheson, MD 
ix) Justin Schaffer, MD 
x) Robert Smith, MD 
xi) Mohanad Hamandi, MD 
xii) Ronald Baxter, MD 
 
Background: 
 
Prolonged and excessive narcotic usage in the postoperative setting has been linked to multiple 
complications. Use of complimentary pain management techniques such as regional analgesia can 
reduce postoperative pain and narcotic usage. This can enhance patient recovery and improve quality of 
life in the immediate postoperative period. [1] Previous research investigating the benefits of local 
analgesia during cardiac surgery have been limited by the sparse amount of single-center randomized 
controlled trials, particularly evaluating the use of para-sternal injections. 
Of the available studies, the use of local analgesia injections compared to controls has led to improved 
pain scores and overall decreased perioperative opioid usage. Studies have shown this efficacy using 
0.2% ropivacaine, [2] 0.75% ropivacaine, [3] and 0.53% liposomal bupivacaine [4] all compared to 
control groups receiving normal saline injections in the para-sternal area. These studies all used 
injections just prior to sternal closure and no significant evidence is available for the use of ultrasound-
guided regional block of the sternum prior to surgical incision. Injection of analgesia prior to surgical 
incision has been shown to decrease postoperative pain compared to injection after surgical closure. [5] 
Hypothesis/Aims:  
 
We hypothesize that injection of 1.3% liposomal bupivacaine and 0.5% bupivacaine (20mL dose) as a 
sternal block prior to surgical incision will lead to decreased pain and opioid usage in the intraoperative 
and postoperative setting for patients undergoing upper mini- and median sternotomy compared to 
controls (normal saline block). 
 
Aim 1: To demonstrate decreased postoperative opioid usage and decreased pain scores in the 
postoperative setting in the treatment group compared to controls. 
 

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The amount of opioid medications used will be recorded during the routine postoperative course. Pain 
scores, set by a validated system, will be obtained daily during the routine postoperative course. 
 
Aim 2: To demonstrate decreased intraoperative opioid usage in the treatment group compared to 
controls 
 
 
Aim 3: To demonstrate improvement in key clinical components closely linked to narcotic usage. 
 
Multiple variables specific to opioid usage will be recorded during the routine postoperative setting. 
These included, but are not limited to: time to extubation, incentive spirometer volume, return of bowel 
function, postoperative atrial fibrillation incidence, delirium and intensive care unit (ICU) and overall 
lengths of stay (LOS). 
Methods 
This is an investigator-initiated prospective randomized study with an 18-month patient accrual period 
and patient follow-up period dependent on postoperative length of stay following surgery. 
Regional Block: Liposomal Bupivacaine (1.3%) solution (20 mL dose) is proposed for use during this 
study. This solution has demonstrated increased efficacy in prolonged analgesia following injection. This 
solution will be injected as an ultrasound-guided subpectoral interfacial plane block.  
Normal Saline: Normal saline (0.9%) will be used as the control solution for patients not receiving the 
liposomal bupivacaine solution. Injection procedure of this solution will be identical to that of the 
liposomal bupivacaine solution. 
Procedures: Patients undergoing a surgical procedure through mini- or full sternotomy will be 
considered for inclusion in this study. Qualified patients will be randomized 1:1 to a liposomal 
bupivacaine sternal block or a normal saline block. An unblinded research coordinator will use a 
password-protected spreadsheet to randomly generate the subject’s randomization assignment. The 
unblinded coordinator will communicate the information to the unblinded anesthesiologist who will 
perform the block. This ensures the intraoperative (including a blinded anesthesiologist and surgeon) 
and postoperative staff (including the blinded research coordinator) will remain blind to the 
randomization assignment.  The subject will also be blinded to the assignment.  The amount of opioid 
medications given by the anesthesia team during the procedure will be recorded. Anesthesiologists will 
be encouraged to standard of care early extubation. There will be no deviation from routine surgical 
procedures following injection of para-sternal solution prior to surgical incision. Patients are considered 
part of the research study until they are discharged. After discharge, patients can be told which block 
they were given and the blinded coordinator can be unblinded to review all medical records. 
 
Study Population  
Patients undergoing a surgical procedure through mini- or full sternotomy from 7/1/2019 at THHBP will 
be included in this data set. A total of 150 patients is proposed for this study.  
Inclusion Criteria: 
1. Age greater than 18 years 
2. Undergoing a surgical procedure through mini- or full sternotomy.  
Exclusion Criteria: 
1. Clinical instability 

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2. Allergic to liposomal bupivacaine solution or any of its ingredients 
3. Maximum-allowed dosage of local analgesia will be exceeded by the injection amount of 
liposomal bupivacaine used in this study (<50 kg).  
4. BMI >45  
5. Pregnant or nursing  
6. Chronic home opioid usage  
7. LVEF< 30% 
8. Low cardiac output requiring mechanical or inotropic support 
9. End-stage renal disease 
10. Cirrhosis  
11. Re-do sternotomy 
12. Endocarditis 
 
Data elements 
Patient Characteristics: 
1. Age 
2. Gender 
3. BMI 
4. Tobacco use 
5. Chronic lung disease 
6. Diabetes 
7. HTN 
8. HLD 
9. Ethnicity (Hispanic & not Hispanic) 
10. Race (Caucasian, African Americans, Asians and others) 
11. CKD 
12. CVA 
13. Chronic home NSAID use (excluding ASA) 
Intraoperative Variables: 
1. Type of procedure being performed 
2. Prior procedures performed 
Postoperative Variables: 
Time to extubation, time to ambulation, time to oral diet, return of bowel function (bowel movement), 
postoperative atrial fibrillation incidence (through discharge), and intensive care unit (ICU) length of stay 
(LOS) and overall LOS. Maximum incentive spirometer maximum volume at 24, 48 and 72 hours, 
Confusion assessment method (CAM) at 24, 48 and 72 hours, post op opioid usage up to 72 hours post 
op. If additional days of post-op opioid usage is documented in the existing medical record, this may be 
used also. CAMs are performed by the blinded research coordinator. 
Pain scores (Scale 0-10) at 1, 2, 4, 8, 12,24,36,48, 60, and 72 hours after ICU arrival for extubated 
patients and CPOT scores (Scale 0-8) for intubated patients 
Adverse Events: Allergic reaction, pneumothorax, pericardial tamponade, vascular injury, hematoma, 
intravascular injection, wound infection, paresthesia, persistent numbness. These adverse events will be 
monitored and reported from the start of the study procedure to discharge (study termination). 

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Protocol Deviations:  If certain data elements are not in the existing medical record and were not 
collected, this is not a protocol deviation.  Nevertheless, all effort will be made to collect these data 
points.  
Funding:  CVRRC  
 
Journals in which you plan to publish or meetings where abstracts will be submitted: TBD 
 
Risks and Benefits 
 
Risks: The risks are the same as the Standard of Care surgery performed outside this study.  This 
is discussed in the ICF.  A confidentiality breach is a risk associated with research. However, all 
data collection protocols follow HIPAA guidance. 
 
Benefits: If participants receive the drug, they could experience less pain than those that don’t 
receive the drug.  However, not all participants are likely to   benefit from the proposed 
research. The investigators will benefit from the knowledge gained, as it will provide deepened 
insight on the main challenges, advantages and disadvantages of the procedure. 
 
 
Data Analytic Methods 
The mean, standard deviation, median, and interquartile ranges of narcotic usage (in morphine 
equivalent units) will be reported for each group. The difference of narcotic usage between the two 
groups will be reported as a single value. Additional variables analyzed in this study include the 
following: 
Patient Characteristics: 
1. Age 
2. Gender 
3. BM 
4. Tobacco use 
5. Chronic pain medication usage 
6. Diabetes 
7. HTN 
8. HLD 
9. Race & Ethnicity 
10. CKD 
11. CVA 
Intraoperative Variables: 
1. Type of procedure being performed 
2. Prior procedures performed 
Postoperative Variables: 
1. Time to extubation 
2. Time to ambulation 
3. Time to oral diet (solid foods) 
4. ICU LOS 
5. Total LOS from date of sternotomy 
6. Return of bowel function 
7. Postoperative atrial fibrillation  

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8. Maximum spirometry at 24, 48, 72 hours post op 
9. CAM at 24, 48, 72 hours post op 
10. Pain Scores (Scale 0-10) at 1, 2, 4, 8, 12,24,36,48, 60, and 72 hours after ICU arrival for 
extubated patients and CPOT scores (Scale 0-8) for intubated patients 
11. Post op opioid usage up to 72 hours post op 
 
Standard descriptive statistics will be used throughout (mean, range, standard deviation, and median, 
IQR), with comparative statistics for normally and non-normally distributed data with p<0.05 considered 
as significant. For categorical variables, 2 Sample t-test or chi-squared test will be used to determine 
statistical significance. For continuous variables, logistic regression will be used to determine the value 
of significance to variables with postoperative outcomes. Depending on the enrollment rate, the 
stratification of data based on the type of sternotomy (full or mini) could be performed and analyzed 
respectively.   
 
 
References 
 
1. 
Bignami, E., et al., Perioperative pain management in cardiac surgery: a systematic review. 
Minerva Anestesiol, 2018. 84(4): p. 488-503. 
2. 
Dowling, R., et al., Improved pain control after cardiac surgery: results of a randomized, double-
blind, clinical trial. J Thorac Cardiovasc Surg, 2003. 126(5): p. 1271-8. 
3. 
Barr, A.M., E. Tutungi, and A.A. Almeida, Parasternal intercostal block with ropivacaine for pain 
management after cardiac surgery: a double-blind, randomized, controlled trial. J Cardiothorac 
Vasc Anesth, 2007. 21(4): p. 547-53. 
4. 
Lee, C.Y., et al., A Randomized Controlled Trial of Liposomal Bupivacaine Parasternal Intercostal 
Block for Sternotomy. Ann Thorac Surg, 2019. 107(1): p. 128-134. 
5. 
Labrum, J.T.t. and A.M. Ilyas, Preemptive Analgesia in Thumb Basal Joint Arthroplasty: 
Immediate Postoperative Pain with Preincision versus Postincision Local Anesthesia. J Hand 
Microsurg, 2017. 9(2): p. 80-83.