Comparison of Preoperative Ultrasound Guided Pectoralis Nerve Block Placement Versus Intra-operative Placement: A Prospective Randomized Trial
Phase: NA
Conditions: Post-operative Pain
Sponsor: University of California, Davis

Comparison of Preoperative Ultrasound Guided Nerve Blocks to Intraoperative Nerve Block Catheters 
for Breast Reconstruction: A Prospective Randomized Trial  
NCT03201809 
6/21/2018 
 

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1) 
Protocol Title 
Title: Comparison of Preoperative Ultrasound Guided Nerve Blocks to 
Intraoperative Nerve Block Catheters for Breast Reconstruction: A Prospective 
Randomized Trial        
Protocol Version Date: 6/21/18 
 
2) 
Objectives 
Aim 1: Report the efficacy and safety of pectoralis nerve blocks for breast 
reconstruction surgery in a prospective fashion 
• Hypothesis: we anticipate >90% efficacy of all pectoralis nerve blocks and 
no complications  
Aim 2: Comparison of intraoperative versus preoperative placement of pectoralis 
nerve blocks 
2A: Comparison of block efficacy and safety 
• Hypothesis: We anticipate a significantly better block efficacy with intra-
operatively placed block catheters as opposed to pre-operatively placed 
blocks, as intra-operatively placed blocks are done under direct 
visualization and can be left in place. We anticipate no difference in safety 
profile.  
2B: comparison of secondary outcomes, such as cost, block placement time, post-
op nausea/vomiting, patient satisfaction, and operative times.  
• Hypothesis: We anticipate a faster overall time (From admission to 
clearance for PACU discharge) with intra-operatively placed blocks. We 
anticipate use of less inhalational anesthesia with pre-operatively placed 
blocks. We anticipate no difference in secondary outcomes, such as post-
operative nausea and vomiting, narcotic use and patient satisfaction 
between the two block groups.  
 
3) 
Background 
Level 1 data shows improved post-operative analgesia with decreased anesthetic 
and opiate use, decreased hospital length of stay, and improved patient satisfaction scores 
with the use of regional nerve blockade.1-5 Using nerve blocks to limit general anesthesia 
(GA) and improve post-operative analgesia is additionally important due to the mounting 
evidence that volatile anesthetics and opioid analgesics impair immune function6,7, and 
increase the risk of ileus, thromboembolism and myocardial infarction8. Despite these 
advantages, the use of regional nerve blockade is still limited to selected cases.  
Pectoral nerve (Pecs) blocks are ultrasound guided inter-fascial plane blocks that 
target the tissue planes between the pectoralis major and minor (Pecs I), and pectoralis 
minor and serratus anterior muscles (Pecs II)9,10.  Targeting these planes with local 
anesthetic blocks the medial and lateral pectoral nerves, anterior divisions of the thoracic 

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intercostal nerves from T2-T6, long thoracic nerve, and thoracodorsal nerves providing 
analgesia to the anterior and lateral thoracic walls with an extension into axilla. Pecs 
blocks have shown excellent efficacy in post-operative analgesia after breast surgery11.  
The main disadvantages of the traditional Pecs blocks are the need for ultrasound trained 
personnel, increased anesthesia wait times as well as the need for a secondary procedure. 
Placement of the blocks under direct visualization addresses these limitations of and may 
allow more accurate plane targeting.  
This research will be significant to the fields of anesthesia/pain management, breast 
surgery and plastic surgery.  With this study, we hope to provide objective, prospective 
data on pectoralis nerve block efficacy and safety. We furthermore hope to examine the 
differences between blocks placed by anesthesia and catheter based blocks placed intra-
operatively by the surgical team, as listed above under Aims.  
 
 
1. Wu J, Buggy D, Fleischmann E, et al. Thoracic paravertebral regional anesthesia 
improves analgesia after breast cancer surgery: a randomized controlled 
multicentre clinical trial. Can J Anaesth 2015: 62: 241-51. 
2. Pei L, et al. Ultrasound-Assisted Thoracic Paravertebral Block Reduces 
Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer 
Surgery: A Randomized, Controlled, Single-Center Trial. 2015: 10: e0142249. 
3. Moller JF, Nikolajsen L, Rodt SA, Ronning H, Carlsson PS. Thoracic 
paravertebral block for breast cancer surgery: a randomized double-blind study. 
Anesth Analg 2007: 105: 1848-51, table of contents. 
4. Abdallah FW, Morgan PJ, Cil T, et al. Ultrasound-guided multilevel paravertebral 
blocks and total intravenous anesthesia improve the quality of recovery after 
ambulatory breast tumor resection. Anesthesiology 2014: 120: 703-13. 
5. Wolf O, Clemens MW, Purugganan RV, et al. A Prospective, Randomized, 
Controlled Trial of Paravertebral Block versus General Anesthesia Alone for 
Prosthetic Breast Reconstruction. Plast Reconstr Surg 2016: 137: 660e-6e. 
6. Procopio MA, Rassias AJ, DeLeo JA, et al. The in vivo effects of general and 
epidural anesthesia on human immune function. Anesth Analg 2001: 93: 460-5 
7. Gong L, Dong C, Ouyang W, Qin Q. Regulatory T cells: a possible promising 
approach to cancer recurrence induced by morphine. Med Hypotheses 2013: 80: 
308-10.  
8. Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief 
and chronic persistent postoperative pain. Anesthesiol Clin North America 2005: 
23: 21-36. 
9. Blanco R. The 'pecs block': a novel technique for providing analgesia after breast 
surgery. Anaesthesia 2011: 66: 847-8. 
10. Blanco R, Fajardo M, Parras Maldonado T. Ultrasound description of Pecs II 
(modified Pecs I): a novel approach to breast surgery. Rev Esp Anestesiol Reanim 
2012: 59: 470-5. 
11. Bashandy GM, Abbas DN. Pectoral nerves I and II blocks in multimodal 
analgesia for breast cancer surgery: a randomized clinical trial. Reg Anesth Pain 
Med 2015: 40: 68-74. 

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12. Bolin ED HN, Wilson SH. Regional Anesthesia for Breast Surgery: Techniques 
and Benefits. Current Anesthesiology Reports 2015. 
 
4) 
Inclusion and Exclusion Criteria 
Individuals will be screened for study eligibility by reviewing the operative schedule in 
advance. Criteria for inclusion will be consenting female patients over 18 years of age 
presenting for immediate breast reconstruction with sub-muscular tissue expander 
placement with or without acellular dermal matrix sling. Patients with a history of 
chronic opioid use, brachial plexus injuries, or planned alternate regional anesthesia will 
be excluded from the study. Individuals under 18 years of age, pregnant women, 
prisoners and patients unable to provide consent will additionally be excluded.  
 
5) 
Study Timelines 
Subjects will be approached up to three days prior to their surgery to make them aware of 
the study. They will sign consent on the day of surgery. Pectoral nerve blocks will be 
placed in the operating room, either pre-operatively by the anesthesiologist or intra-
operatively by the surgeon. Post-operative care will be routine. Pain surveys will be 
emailed out via redcaps at 6h, 12h, and 24h post-operatively, as well as on days 2-7. A 
satisfaction survey will be emailed to the patient one week after surgery. After the 
satisfaction survey, patient participation will be complete.  
 
We anticipate completing our enrollment in 5 years, and completing data analysis by six 
months after the final patient has been enrolled.  
 
6) 
Study Endpoints 
The primary study endpoint will be after completion of study (after surgery and survey 
completion) of 252 patients (126 in each treatment arm). Secondary endpoints include 
time to PACU clearance and time to hospital discharge. Because the intervention is a 
single-shot injection, there are no specific safety endpoints. Please see below for a 
discussion of potential adverse from the pectoralis nerve blocks.  
 
7) 
Procedures Involved 
Subjects presenting for immediate breast reconstruction and meeting inclusion criteria 
will be approached pre-operatively to make them aware of the study. On the day of 
surgery, patients will be asked to sign consent for the study. Patients who sign consent 
will then undergo randomization to a study arm (pre-op placement of intra-op catheter 
placement). Randomization will be done by study personnel using the i-phone application 
“Randomizer.” Randomization will follow a blocked scheme; that is, if one patient is 
randomized to the anesthesia block group, the next will automatically get the catheter 
treatment.  This will ensure equal numbers in both study arms. After consent and 
randomization is complete, patients will be told of their study arm. Patients will then be 
asked to fill out a pre-operative pain survey discussing their baseline level of breast pain.  
 
For those randomized to the pre-op placement arm, anesthesia will perform this block 
prior to surgery but after their pre-operative survey is complete.  The anesthesia 

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department is already performs pectoralis nerve blocks on selected patients, and have the 
work flow set up for this. The dose will be 10 mL of 0.25% Ropivicaine for the pecs 1 
injection, and 20 mL of 0.25% Ropivacaine for the pecs 2 injection. Ropivacaine is a 
standard sodium channel blocking anesthetic already FDA approved for peripheral nerve 
blocks. For those randomized to the intra-operative arm, catheter placement will be 
performed after the pectoralis muscle flap has been raised, for more accurate targeting of 
the tissue planes and nerves. Blocks will be performed by the operating surgeon . Instead 
of single shot blocks, a commercially available On-Q nerve block catheter (Halyard 
Health, Alpharetta, Georgia) will be placed. Through these catheters, 0.2% Ropivacaine 
will be instilled at 4 mL/hr for a total of 400 mL (amount in standard On-Q reservoirs). 
Vitals are continuously monitored in the operative suite and in the Post Anesthesia Care 
Unit (PACU), with a high level of supervision by the anesthesiology team. In the very 
rare event of an adverse reaction to the injection, appropriate action will be taken 
immediately and in accordance with standard work-flow for local anesthetic toxicity 
(epinephrine for severe allergy or circulatory support, intravascular lipid emulsion and 
sodium bicarbonate for overdose, although our doses should not be high enough to 
precipitate this, even with inadvertent intravascular injection). If hypoxia not due to 
opioids and not responsive to supplemental oxygen is present, a chest radiograph will be 
ordered to rule out pneumothorax from inadvertent visceral pleural puncture.  
 
Post-operatively, the patients will be monitored in the PACU.  They will have standard 
anesthesia pain and nausea management orders written for (these are ordered en bloc as 
part of an already existing order set). PACU nursing staff will dose medications 
according to the written orders. PACU clearance time (which is currently time-stamped 
in the chart by the PACU resident) will be noted. Often patients will remain in PACU due 
to ward over-crowding, so actual time of PACU discharge will not be noted. Post-PACU 
hospital course will proceed as is standard of care, with PRN pain and nausea medication 
ordered. Standard hospital discharge criteria will be used for all groups.  
 
Information will be collected from all subject’s hospital stays, including time in pre-op 
holding area, time under general anesthesia, duration inhalational anesthetic, amount of 
narcotic used in morphine equivalents (divided into OR amount, and amounts in first 6, 
12, 18 and 24 hours after surgery) after surgery, incidence of nausea/vomiting, number 
and amount of antiemetic used (same time intervals as above), pain scores overall and by 
breast on the 0-10 analog scale (average over the same time intervals), time of PACU 
clearance, and time of hospital discharge. In addition, a RedCaps survey with questions 
about the patient’s pain level will be emailed pre-op and at post-op hours 6,12,24 and 
days 2-7.  
 
For patients with pain catheters, these catheters will be removed at the patient’s regularly 
scheduled post-operative appointment (generally POD 4 or 5). On-Q balls will not be 
refilled such that all catheter patients will have infusion for the same amount of time.  
 
One week after hospital discharge, subjects will be emailed a short survey through the 
RedCap survey system (see supplemental forms for survey questions). Hospital billing 

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will be examined with the assistance of the billing department using CPT codes and using 
publically available cost data.  
 
 
 
8) 
Data and/or Specimen Management and Confidentiality 
During the review, the investigator (or research staff) will record data collected in 
a manner that includes indirect identifiers. Additionally, a single location will 
include indirect and direct identifiers (to match the two). 
To elaborate: Subjects will be identified by a unique study ID (A = pre-op 
placement, B = intra-op placement; so 1A would be the first patient enrolled in 
the pre-op placement group). An enrollment log, including a “crib sheet” 
identifying patients by their study ID and their consent paperwork, will be kept in 
a binder. That binder will be stored in a locked cabinet in the plastic surgery Lab 
in Research Building 2.  After the IRB has been closed, study consents will be 
maintained for 3 years, and HIPAA consents for six years, in compliance with 
IRB rules and regulations.  Any data compiled off of the Electronic Medical 
Record (EMR) will be identified by subject ID only and collected onto a 
spreadsheet on the PI’s password protected computer.  
With respect to the surveys, Redcap is a mature, secure web application that has 
been used successfully by many other investigators at our institution to collect 
secure survey data.  
Data analysis will be done using http://vassarstats.net. Statistical comparisons will 
be performed across the study groups using T-test for two-group comparisons. 
 
All research personnel will be up to date with their HIPAA training.  
 
For our power analysis, we set our alpha = 0.05 and beta (power) = 0.8. Using the 
Bashandy et al. paper1, the mean morphine requirement in the PACU was 2.9 ± 
1.861 mg for the Pecs block group, and 6.9 ± 1.861 mg for the control group (p < 
0.001). Based on our preliminary experience with pre-operatively placed pecs 
blocks, we estimate that they work well about 70% of the time. If we hope to see 
a 20% improvement with more accurate plane targeting, then our average 
morphine requirement in the intra-operative placement group would be 2.3 mg. 
Therefore, we would have to enroll 126 patients in each arm to have an 80% 
chance of seeing a difference, if there truly is one.  
1. Bashandy GM, Abbas DN. Pectoral nerves I and II blocks in multimodal 
analgesia for breast cancer surgery: a randomized clinical trial. Reg 
Anesth Pain Med 2015: 40: 68-74. 

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9) 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
The EMR of every subject who completes the injection portion of this study will 
be assessed within 24 hours of pectoralis nerve block placement. Any untoward 
events, such as intravascular injection, allergic reaction, pneumothorax or other 
unanticipated event will be assessed for its causative relationship to the pectoral 
nerve block  . We anticipate these to all be very unlikely, as the current literature 
on the pectoralis nerve blocks report a 0% complication rate (see citations, 
above). If a serious adverse event occurs, these will be reported immediately to 
the IRB and will be a trigger for an immediate suspension in enrollment and a 
review of the injection protocol with the Chiefs of both the Departments of 
Anesthesiology and Surgery. If any performer error can be identified and 
corrected, then with approval from the departments enrollment will continue. If 
not, the study will be terminated.  
We will cumulatively review the data after 20 subjects in each study arm have 
been enrolled, and then again at 50 patients, 75 patients, 100 patients, and 126 
patients.  
 
10) Withdrawal of Subjects 
There are limited circumstances in which a patient would be withdrawn from 
research, particularly without their consent. The only circumstance would be in 
the case of aborted tissue expander placement. If the plastic surgeon does not feel 
that the mastectomy flaps can support the added stress of an expander, then the 
plastic surgery portion of the procedure is aborted (standard protocol). In this 
circumstance, the pre-op block arm will already have gotten a block. No intra-
operative catheters will be placed. After awakening from anesthesia, the patient 
will be alerted to their expulsion from the study, and no other data would be 
collected regarding their hospital stay, and no survey information collected.  
Of note, a single patient was enrolled into the control arm of the study prior to this 
arm being abolished. This patient’s survey data has already been collected but 
will not be used for data analysis. Their hospital data will not be collected.  
 
11) Risks to Subjects 
The main foreseeable risk to study subjects is that the nerve block would not work 
well. In this event, subjects would be appropriately treated with adjunctive pain 
medications.  
Two very rare risks – never reported in the literature, so currently theoretical 
rather than described – are intravascular injection and pneumothorax, as outlined 
above. These could have potentially serious consequences, such as bupivacaine 
toxicity (at worst, leading to hypotension or seizure) or hypoxemia requiring chest 
tube placement and potentially other procedures. However, pectoralis nerve 
blocks have been in use for over 5 years, and more risky blocks, including the 
paravertebral block and intercostal block (both of which have higher rates 

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reported of the above complications) for over 30 years. Therefore, these risks are 
generally considered to be outweighed by the benefits of peripheral blocks.  
 
With respect to the nerve catheters, potential risks to patients with placement are 
less than with the ultrasound guided block, as these catheters are placed through 
the skin and into the mastectomy pocket under direct visualization. Additional 
risks would include the small risk of a post-operative infection related to the 
catheter. This risk will be minimized by sterile placement, a sterile dressing, and 
expeditious removal of the catheter within the first post-operative week. As these 
catheters are standard of care at UC Davis currently, this risk is generally felt to 
be acceptable.  
 
12) Potential Benefits to Subjects 
Study subjects potentially will have decreased anesthetic requirements and improved 
post-operative pain control. Decreased general anesthesia could mean less postoperative 
nausea/vomiting. Improved pain control will lead to less narcotic use and therefore may 
decrease the chance of ileus, nausea, itching and other common narcotic side effects.  
 
13) Sharing of Results with Subjects 
No additional information will be shared with subjects. 
 
14) Provisions to Protect the Privacy Interests of Subjects 
Patients will be approached about enrolling in this study in the preoperative area. Patient 
beds in this area are one bed per room; therefore, the conversation will be in private, 
between the physician and patient. Family members may be present, but this is standard 
for all preoperative consents (anesthesia consents, block consents, sometimes surgical 
consents if they are not on file). The consent process will specifically site that refusal to 
enroll will not result in any penalty, including any withholding of pain medication in the 
future. Post-operatively, no specific research contact will be made until an online 
questionnaire is sent out by email. 
 
15) Compensation for Research-Related Injury 
There is no specific compensation for study participation.  Because breast reconstruction 
is a planned procedure, all patients undergoing surgery will have insurance. Nerve blocks 
are a billable procedure, recognized by insurance companies. Any complications related 
to the procedure will likewise be covered by insurance.  
 
16) Economic Burden to Subjects 
As outlined above, the cost of the nerve blocks will be covered by insurance, and no 
additional out of pocket funds requested. There is no downtime or leave time required for 
these nerve blocks – in fact, if there is a decrease in narcotic use, then the nerve blocks 
may even hasten subject’s ability to return to work.