OBJECTIVES
The primary objectives of the pilot trial are to demonstrate feasibility of recruitment and
to demonstrate efficacy potential. The primary objectives of the definitive trial are to
determine if Thoracic Paravertebral with Pecs blocks (defined as Pec I and Pec II blocks)
(TPVB+Pecs) will reduce opioid consumption and chronic pain compared to a TPVB+Sham block in
patients undergoing mastectomy with IBR using tissue expanders or implants. Secondary
objectives of the definitive trial include assessment of opioid consumption, patient-reported
postoperative pain scores, postoperative nausea and vomiting, length of stay, and
patient-reported quality of recovery.
HYPOTHESIS
In breast cancer patients undergoing mastectomy with immediate implant-based breast
reconstruction, the addition of a Pecs block to a thoracic paravertebral block (TPVB+Pecs)
will reduce acute and chronic patient-reported postoperative pain as compared to a thoracic
paravertebral block with sham Pecs block (TPVB+Sham).
Secondary hypotheses include: the TPVB+Pecs over TPVB+Sham will decrease opioid consumption,
postoperative nausea and vomiting, decrease patient-reported postoperative pain scores,
length of stay, and improve patient-reported quality of recovery in patients undergoing total
mastectomy with IBR using tissue expanders or immediate implants.
JUSTIFICATION
The definitive trial will determine if TPVB+Pecs improves postoperative acute and chronic
pain and reduces opioid use for patients undergoing mastectomy with IBR using tissue
expanders or immediate implants.
International Consensus guidelines for ERAS in breast reconstruction make a strong
recommendation for multimodal, opioid-sparing analgesia postoperatively based on high-level
evidence. Increased total opioid analgesic use has been shown to increase length of stay in
hospital. Reduced opioid consumption results in less postoperative nausea, vomiting, and
constipation, supports early ambulation, shortens hospital stays, and improves psychological
well being. Current ERAS protocols for alloplastic breast reconstruction are successfully
opioid-sparing and address acute recovery. However, opioids continue to play an important
role in peri-operative protocols for achieving adequate pain control, which suggests further
adjunctive strategies may be beneficial. Furthermore, the effects of peri-operative protocols
on the development of chronic pain are lacking. By evaluating the effectiveness of TPVB+Pecs
in alloplastic reconstruction, our proposed study would help to establish an important
additional feature to the ERAS pathway for our hospital and other institutions.
STUDY DESIGN
The design of the pilot RCT is the same as the future definitive trial, a parallel-group,
double-blinded RCT. The target population includes patients undergoing mastectomy with IBR
using tissue expanders or immediate implants.
The study will compare two arms:
TPVB using local anesthetic infiltrate with Pecs using local anesthetic infiltrate
(TPVB+Pecs, the intervention arm).
OR
TPVB using local anesthetic infiltrate with Pecs using normal saline infiltrate
(TPVB+Sham, the control arm).
The pilot trial will be conducted at Mount Saint Joseph Hospital (MSJH). The assignment of
intervention will be determined by randomization through REDCap.
Each participant will be assigned a consecutive Study ID at time of enrollment. Patients will
be randomized 1:1 to either TPVB+Pecs or TPVB+Sham. Patients undergoing symmetrizing
procedures as part of a bilateral breast surgery will not have a regional block on the
symmetrizing side (which is not IBR). Patients undergoing bilateral IBR surgery using
implants or expanders on both breasts will not be included in the study due to risk of local
anesthetic toxicity with bilateral TPVB.
The randomization sequence will be created using REDCap-generated 1:1 randomization with
permuted blocks of varying size (4 and 6). The assignments (TPVB+Pecs or TPVB+Sham) will be
placed in order in opaque, consecutively numbered envelopes. The sequence and envelopes will
be created by an independent research assistant who will not be involved in the remainder of
the study implementation.
Study participants, Operating Room (OR) anesthesiologists, surgeons, research assistants, and
nurses in the OR, Post-anesthesia Care Unit (PACU), and ward will be blinded as to whether a
participant receives TPVB+Pecs or TPVB+Sham block. At MSJH, the anesthesiologists in the
operative theater are separate from the team of regional anesthesiologists performing
regional blocks in the preoperative area. Only the regional anesthesiologist and anesthesia
assistant in the preoperative block area, who will administer the regional block, will be
unblinded.
On the day of surgery, the regional anesthesiologist at MSJH will be provided with the Study
ID specific sealed envelope which will assign the patient to receive either the TPVB+Pecs or
TPVB+Sham block. The regional anesthesiologist will prepare local anesthetic or normal saline
injections for infiltration based on the random assignment. For all patients, the regional
block will be performed as outlined in the Procedure Protocols (See Appendix 1: Nerve Block).
All participants will receive general anesthesia following the nerve block. All other
parameters and protocols will be identical.
Currently, at MSJH, approximately 4 - 5 cases of mastectomy with IBR are performed per week.
We do not anticipate difficulty with enrolment into this study. This internal pilot will
generate initial recruitment data to enable an early review and validation of our recruitment
projections and study population target prior to transition to formal RCT.
Additional Details of Study Design
Participants will also be given at the time of consent a post operative package. This will
contain the Quality of Recovery-15 Questionnaire (Form 7), Recovery Booklet (Form 5) and Pain
Burden Index (Form 8).
The Quality of Recovery-15 Questionnaire (see Form 7) is to be completed at 24 hours after
surgery in paper format or electronic format (based on their preference). This 24 hour time
point will be marked on the QoR-15 form. If paper format is preferred, the QoR-15 will be
provided with a paid-postage envelope to return once completed at 24 hours after surgery. The
pain NRS at 24 hours will be recorded from the chart. The envelopes will be addressed to the
research coordinator at UBC Hospital office. If the participant prefers electronic format,
the questionnaire will be sent to their provided email address using secure online format
(REDCap developed questionnaire).
Recovery Booklet (see Form 5) will include: a) schedule for taking prescription pain
medications; b) a postoperative 7-day symptom diary (for recording pain on NRS at 24 hours,
episodes of vomiting, nausea, and use of prescribed medications). Patients will be provided
with a paid-postage envelope to return their Recovery Booklet via mail once completed 7 days
after surgery. Patients will be reminded to complete the Recovery Booklet (Form 5) in 3-4
days and once again at 14 days to return the envelope.
The Pain Burden Index questionnaire (see Form 8) asks specifically about pain in four
surgically related body areas and to calculate the Pain Burden Index (PBI). The PBI is
calculated by summing the pain severity scale (0-10) at each of four locations (breast,
axilla, chest wall, arm) multiplied by the frequency of the pain at each site. The PBI
questionnaire will be sent to participants via mail as paper format (with paid-postage
envelope to return once completed) or email as electronic format (as per their requested
preference) to be completed 3 and 6 months after their surgery. Details of present adjuvant
treatments (radiation and chemotherapy) will also be included in the questionnaire.
Secondary outcomes data including opioid consumption and side effects, length of stay in
hospital (hours), rescue medications, failure of early discharge, complications and adverse
events and time-based outcome measures (time in PACU, time under general anesthesia, time to
perform ultrasound-guided TPVB+PecsII, failure of discharge from PACU and requiring
admission) will be collected through participants' charts and EMR.
STATISTICAL ANALYSIS
Patient characteristics and outcome measures will be summarized by group. An 80% confidence
interval for the difference in average pain score over 24 hours will be calculated.
