Clinical trial NCT03638635
Conditions: Opioid Use Pain, Postoperative Colectomy Colorectal Surgery
Keywords: Bupivacaine Exparel TAP Block Opioids Narcotics ERAS
Sponsor: Inova Health Care Services
Start date: 2018-05-14; Completion date: 2019-01-16
Enrollment: 63 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The transversus abdominis plane (TAP) block can be used to reduce pain in patients who get abdominal surgery. TAP blocks are given with a local anesthetic. The purpose of this study is to compare pain medication usage after surgery between two different types of local anesthetic: liposomal bupivacaine and standard bupivacaine.

Detailed description:
Pain control is a factor that is central to the surgical patient's postoperative experience. Opioid pain medications are a mainstay of postoperative pain management. However, these have several adverse effects.

Multimodal pain regimens to minimize opioid use have become central to enhanced recovery after surgery (ERAS) protocols. The transversus abdominis plane (TAP) block is one intervention that contributes to this regimen. Traditionally, TAP blocks are performed with local anesthetics such as bupivacaine. More recently, these have also been performed with liposomal bupivacaine, whose duration of action is much greater than regular bupivacaine (96 hours versus 8-9 hours, respectively).

In this study, postoperative opioid usage will be compared between patients receiving regular bupivacaine and liposomal bupivacaine.

Arms: arm 1: Standard (0.25% bupivacaine) bupivacaine (133 mg in 10mL, diluted with 20 mL saline) will be injected into the fascial layer between the internal oblique and the transversus abdominis with ultrasound guidance, 30 mL per side for a total of 60 mL. arm 2: Liposomal bupivacaine (133 mg in 10mL, diluted with 20 mL saline) will be injected into the fascial layer between the internal oblique and the transversus abdominis with ultrasound guidance, 30 mL per side for a total of 60 mL.
Interventions: intervention 1: Bupivacaine intervention 2: Bupivacaine liposome
Intervention descriptions: intervention 1: Abdominal injection of bupivacaine into fascial layer. intervention 2: Abdominal injection of bupivacaine liposome into fascial layer.

Protocol documents:
Prot_SAP_000.pdf: 
 
1 
 
 
TAP Blocks Performed with Bupivacaine Versus Liposomal 
Bupivacaine in Colorectal Surgery Patients: A Prospective, Cluster 
Randomized Trial 
 
 
Principal Investigator:  
Donald Colvin, MD, FACS, FASCRS 
 
Sub-Investigator(s):  
Cecilia Birisan, MD;  
Jay Iaconetti, MD;  
Chang Liu, PhD, MA; 
Lynda S. Dougherty, MD, FACS, FASCRS; 
Daniel P. Otchy, MD, FACS, FASCRS;  
Lawrence E. Stern, MD, FACS, FASCRS;  
Kimberly A. Matzie, MD, FACS, FASCRS;  
Caroline Sanchez, MD, FASCRS; 
Katherine W. Khalifeh, MD, FACS, FASCRS; 
Timothy A. Plerhoples, MD, MPH 
 
 
 
 
Sponsor:  
N/A 
 
 
Site of Investigation:  
Inova Fairfax Hospital 
 
 
Date of Protocol:  
September 26th, 2018 
 
 
 
 
 
 
 
 
 
 
 


 
2 
 
ABSTRACT 
 
Title: TAP Blocks Performed with Bupivacaine Versus Liposomal Bupivacaine in Colorectal 
Surgery Patients: A Prospective, Cluster Randomized Trial 
 
Short Title: TAP Blocks: Bupivacaine versus Exparel 
 
Rationale: Multimodal pain regimens to minimize opioid use have become central to enhanced 
recovery after surgery (ERAS) protocols. The transversus abdominis plane (TAP) block is one 
intervention that contributes to this regimen. Patients who receive TAP blocks prior to colorectal 
operations have been shown to have reduced opioid consumption and length of stay compared to 
patients who do not. TAP blocks can be performed with local anesthetic, such as bupivacaine. More 
recently, these have been performed with liposomal bupivacaine, which is released over a period of 
96 hours rather than metabolizing over 8-9 hours. However, very little retrospective data comparing 
regular versus liposomal bupivacaine exists, and results have been mixed. No prospective 
randomized studies have compared these two forms of the drug.  
 
Objectives: This study aims to compare opioid consumption in colorectal patients receiving 
preoperative TAP blocks of either regular or liposomal bupivacaine. Secondary objectives would 
compare postoperative pain scores, total amount of pain medication use (opioid and non-opioid), 
time to patient mobilization, time to return of bowel function, length of stay, antiemetic use, 
complications, readmissions, mortality, and hospitalization costs between these two groups. 
 
Study Type: Prospective, Cluster Randomized Trial 
 
Study Design: Power analysis indicates that a minimum of 101 patients per group should be 
enrolled. Patients will be approached for consent if they are 18 years of age or older and underwent 
elective colectomy by the surgeons of Fairfax Colon and Rectal Surgery. Exclusion criteria are the 
following: patients under age 18, patients unable to receive TAP block due to allergy, 
contraindication, or other reason, patients unable to provide consent, pregnant patients, patients on 
chronic opioids, patients undergoing emergent operations, patients undergoing loop ileostomy 
reversal and abdominoperineal resections, patients who primary language is not English or Spanish, 
and patients who received the TAP block with local anesthetic off of the cluster randomization 
assignment. 
 
Study Methodology: Patients will receive a preoperative TAP block with either regular or 
liposomal bupivacaine. Each drug will be alternately used as the practice standard of care until an 
adequate number of patients are enrolled. The drugs will be alternated for four month periods for the 
first cycle, followed by two month intervals. Patients will be approached postoperatively to consent 
to use of their data for research purposes. Both drugs are currently FDA approved and both are 
routinely used for TAP blocks; the current understanding based off of scant literature is that there is 
clinical equipoise between the two drugs. The standard of care postoperative pain management 
regimen and diet advancement protocol will be used for all participants. Pain scores and opioid 
consumption will be recorded and collected in a prospective fashion. 
 


 
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Statistical Methodology: Demographic and clinical factors will be compared between groups 
using t-tests for continuous variables, Pearson’s χ2 tests for categorical variables and rank-based 
methods if necessary. Generalized linear mixed effects model for ordinal outcomes will be 
applied to analyze pain scores under the proportional odds assumption. Daily opioid 
consumption will be analyzed using a linear mixed effects model.  
 
 
1. INTRODUCTION 
 
1.1. Specific Aims 
 
The aim of a multimodal pain medication regimen is to reduce opioid consumption as part of the 
enhanced recovery after surgery (ERAS) protocols. The transversus abdominis plane (TAP) 
block can be used to reduce pain in patients undergoing abdominal surgery. Traditionally, TAP 
blocks are performed with local anesthetics such as bupivacaine.  More recently, these have also 
been performed with liposomal bupivacaine, which has a duration of action much greater than 
regular bupivacaine (96 hours versus 8-9 hours, respectively). To date, no prospective, 
randomized trial has been performed to directly compare TAP blocks performed with liposomal 
and regular bupivacaine. The primary objective of this study is to compare in-hospital 
postoperative opioid consumption in patients who undergo TAP blocks with either liposomal 
bupivacaine or regular bupivacaine prior to colorectal operation. The secondary objectives are to 
compare pain scores, total amount of pain medication use (opioid and non-opioid), time to 
mobilization, time to return of bowel function, length of stay, antiemetic use, 30-day 
postoperative complications, 30-day readmissions, 30-day mortality, and hospitalization costs in 
the same patient population. 
 
1.2. Hypothesis  
Alternative hypothesis: Postoperative in-hospital opioid consumption differs between patients 
who receive TAP blocks performed with liposomal bupivacaine and patients who receive TAP 
blocks performed with regular bupivacaine prior to colectomy.  
 
Null hypothesis: Postoperative in-hospital opioid consumption does not differ between patients 
who receive TAP blocks performed with liposomal bupivacaine and patients who receive TAP 
blocks performed with regular bupivacaine prior to colectomy.  
 
1.3. Background and Significance  
Pain control is a factor that is central to the surgical patient’s postoperative experience. Opioid 
pain medications are a mainstay of postoperative pain management. However, these have several 
adverse effects, ranging from respiratory arrest to slowing of the gastrointestinal tract motility 
causing nausea, vomiting, and constipation. These last few side effects run counter to the goal of 
return of bowel function in patients undergoing colorectal surgery. ERAS protocols emphasize 
the use of multimodal pain regimens to decrease opioid use and thus reduce both morbidity and 
hospital stay for patients. 
 
The TAP block, a type of abdominal field block, is one intervention that has become a part of 
these multimodal regimens. It was first introduced in 2001 by Rafi, and was described as a blind 
technique aimed at placing a single injection of local anesthetic into the lumbar triangle of Petit, 
bordered by the external oblique, latissimus dorsi, and iliac crest1. Since 2007, ultrasound 


 
4 
 
guidance has been used to direct injection of local anesthetic into the fascial layer between the 
internal oblique and the transversus abdominis, through which branches from T9-L1 run to 
innervate the anterior abdominal wall2. Studies investigating the overall effect of TAP block 
have yielded somewhat mixed results. Randomized studies comparing TAP block to local wound 
infiltration or placebo in colorectal patients have shown no significant difference in opioid 
consumption or pain scores3, 4. By contrast, another randomized study demonstrated decreased 
opioid consumption in patients who received TAP blocks when compared to patients who had 
not5. Non-randomized studies performed in colorectal patients have shown that TAP blocks are 
associated with decreased opioid use, time to return of bowel function, and length of stay6, 7, 
contributing to the goals of enhanced recovery pathways. Of note, these studies were all 
performed with regular bupivacaine. 
 
Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals) was introduced in 2012. It is 
formulated as particles that contain microscopic internally aqueous chambers that are separated 
by lipid membranes, allowing for release of unaltered bupivacaine over a period of about 96 
hours.8 By contrast, non-liposomal bupivacaine has a duration of action of a maximum of 8-9 
hours. Liposomal bupivacaine is currently FDA-approved for administration into surgical sites to 
provide postsurgical anesthesia.9 
 
When compared to a multimodal pain regimen following thoracotomy, liposomal bupivacaine 
was found to offer no significant difference in pain control following thoracotomy10. For total 
knee arthoplasty, ropivicaine was actually found to be superior to liposomal bupivacaine11, 12. In 
laparoscopic hysterectomy, local wound infiltration with liposomal bupivacaine was found to be 
no different than standard bupivacaine in terms of postoperative opioid consumption and pain 
scores13. However, when applied in an abdominal field block prior to abdominoplasty, 
administration of liposomal bupivacaine did result in reduced postoperative opioid use and 
earlier mobilization14. Studies comparing administration of liposomal versus standard 
bupivacaine have generated mixed results as well. A study by Haas and colleagues in 2012, one 
of the earliest to assess liposomal bupivacaine, showed that use of the liposomal formulation 
resulted in reduced opioid consumption following hemorrhoidectomy15. However, a more recent 
study comparing local infiltration of liposomal versus regular bupivacaine following colorectal 
procedures noted no difference in postoperative opioid use16. 
 
There are few studies that compare TAP blocks performed with liposomal and regular 
bupivacaine. One study conducted in 2016 compared the two formulations in patients 
undergoing laparoscopic hand-assisted donor nephrectomy and found that liposomal bupivacaine 
TAP blocks resulted in decreased opioid use (expressed in fentanyl equivalents 105 versus 182, 
p=0.03), lower pain scores (5/10 versus 6/10 at 24-48h, p=0.009, and 3/10 versus 5/10 at 48-72h, 
p=0.02), decreased length of stay (67.7 versus 87.1 hours, p=0.02), and fewer complaints of 
postoperative nausea and vomiting17. Of note, the primary author of this study is on the speaker’s 
bureau and acts as a consultant for the drug company Pacira, which produces and sells liposomal 
bupivacaine under the label Exparel. A non-randomized retrospective cohort study published this 
year assessed colorectal patients who were given TAP blocks with liposomal versus regular 
bupivacaine. This study noted that earlier in the postoperative course, pain control scores in the 
liposomal bupivacaine patients were lower; however, at 36-48 hours postoperatively, there was 
no significant difference in pain scores. IV opioid use was decreased, but oral opioid use was 


 
5 
 
unchanged in patients undergoing minimally invasive procedures; in open procedures, there was 
no difference in opioid use. Length of stay and hospitalization costs were found to be the same 
between the two groups18. 
 
Due to its extended duration of action, we have incorporated administration of liposomal 
bupivacaine TAP blocks into our institution’s multimodal pain control regimen following 
colorectal resection, with the aim of reducing opioid use. The aforementioned mixed data 
certainly calls into question whether the increased up-front expense of using liposomal 
bupivacaine can be justified. To date, no prospective, randomized trial has been performed to 
directly compare TAP blocks performed with liposomal and regular bupivacaine. This study 
would generate recommendations for practice regarding which formulation should be used for 
preoperative TAP block. 
 
1.4. Preliminary Studies 
To the investigators’ knowledge, this is the first prospective, randomized study comparing the effect 
of regular versus liposomal bupivacaine TAP blocks on postoperative opioid requirements.  Dr. 
Colvin is a colorectal surgeon who founded Fairfax Colon and Rectal Surgery. He also currently 
holds an academic position as an Associate Professor of Surgery with the Medical College of 
Virginia. When Exparel was first used for TAP blocks at Inova Fairfax Hospital, he spearheaded a 
Quality Improvement project to assess the effectiveness of TAP blocks with Exparel as part of the 
ERAS protocol. 
 
2. STUDY DESIGN AND SUBJECT SELECTION  
 
2.1. Study Type 
This study is a prospective randomized trial designed to compare postoperative opioid 
requirements and pain related outcomes in patients who receive regular or liposomal bupivacaine 
TAP blocks prior to colorectal resection. Participants will receive a transversus abdominis plane 
(TAP) block with either liposomal bupivacaine or regular bupivacaine immediately prior to their 
procedure. Each drug will be used as the practice standard of care for alternating periods; all 
patients undergoing colorectal resection with the surgeons of Fairfax Colon and Rectal Surgery 
will receive the same type of TAP block in each period. The drugs will be alternated for four 
month periods for the first cycle, followed by two month intervals. The two drugs will be 
alternated until an adequate number of patients have been enrolled in the study. Clinical 
equipoise is assumed by clinicians and hypothesized to exist between the two formulations of 
bupivacaine, but previous studies comparing the two medications have produced mixed results. 
Patients will be approached for consent in the hospital postoperatively to request the use of their 
data for research purposes. 
 
2.2. Setting/Location 
The proposed prospective study would take place at Inova Fairfax Hospital, 3300 Gallows Road, 
Falls Church, VA 22042.  
 
2.3. Duration of Study 
We anticipate approximately two years to obtain an adequate number of subjects.  In most cases, 
patients’ active participation in the study would conclude after their initial hospitalization; 
hospital and office records would be actively reviewed for the first 30 days postoperatively for 


 
6 
 
any complications or mortality and 30 days post-discharge for any readmissions. Patients who 
have a hospital stay ending before 1 pm on postoperative day 3 (POD 3) will receive one or two 
phone calls to gather information up until POD 4 from the investigators to collect information on 
pain medication consumption from discharge up until end of day on postoperative day 4.  These 
phone calls would take place within 96 hours of discharge, and only for those patients with a 
discharge prior to 1 pm on POD 3. This is a very rare occurrence due to the average length of 
stay for these procedures being 4-5 days. A note for these phone calls would be entered into the 
patient’s electronic medical record. The only data points to be collected from the patient from the 
phone calls are the same as the ones collected while in the hospital postoperatively, these are 
rows 51-58 on the data collection tool excel (POD0 to POD4).  
 
2.4. Number of Subjects  
By our power analysis, we require a minimum of 101 subjects per group (202 subjects in total). 
Approval will be sought for an enrollment goal of 250 total to allow for growth. 
 
2.5. Study Population 
 
2.5.1. Gender of Subjects 
All patients who qualify under the inclusion criteria will be included, regardless of gender. 
 
2.5.2. Age of Subjects 
All patients who qualify under the inclusion criteria and who are 18 years of age or older will be 
included. 
 
2.5.3. Racial and Ethnic Origin  
All patients who qualify under the inclusion criteria will be included, regardless of racial or 
ethnic origin. 
 
2.5.4. Vulnerable Populations 
Patients under age 18, pregnant women, patients undergoing emergent operations, and 
individuals who are unable to appropriately provide consent for themselves or appropriately 
report pain scores will be excluded from the study population. Primarily Spanish-speaking 
participants who have limited English fluency will be provided with an in-person, telephonic, or 
video interpreter when consent is being obtained.  The consent form would also be translated into 
Spanish. 
 
2.6. Recruitment  
Recruitment will take place in the hospital when patients are approached postoperatively to 
request the use of their data for research purposes. The multimodal pain regimen and the ERAS 
protocol are already explained to patients during the patient’s preoperative visit to the surgeon’s 
office, emphasizing the goal of reducing opioid consumption. All staff who would be obtaining 
consent will receive the appropriate training.  
 
TAP blocks have become an essential component of our institution’s ERAS protocol in order to 
minimize opioid use postoperatively. Thus, unless there is a contraindication, patients will 
receive a TAP block regardless of whether or not they participate in the study. All patients 
undergoing colorectal resection with the surgeons of Fairfax Colon and Rectal Surgery will 


 
7 
 
receive the same type of TAP block (liposomal or regular bupivacaine) in each period, regardless 
of whether or not they participate in the study. These cycles will continue until we have reached 
enrollment goals, up to a 2-year period. 
 
2.7. Inclusion Criteria 
Patients will be approached for consent if they are:  
1. 18 years of age or older 
2. Undergoing elective colectomy by surgeons of Fairfax Colon and Rectal Surgery 
 
2.8. Exclusion Criteria 
Patients will be excluded from the study if they fall into the following categories: 
1. Patients under age 18 
2. Patients unable to receive TAP block due to allergy, contraindication, or other reason 
3. Patients unable to provide consent 
4. Pregnant patients 
5. Patients on chronic opioids.  Patients previously on a regular opioid regimen would need 
to be opioid-free for a period of 1 year for inclusion in the study. 
6. Patients undergoing emergent operations  
7. Patients undergoing loop ileostomy reversal, as this does not require a new incision 
through the abdominal wall 
8. Patients undergoing abdominoperineal resection, pelvic exenteration, or perineal rectal 
prolapse repairs, as the TAP block would not control pain at the perineum 
9. Patients whose primary language is not English or Spanish 
10. Patients who received TAP block with local anesthetic off of the cluster randomization 
assignment (ex. patients receiving liposomal bupivacaine during the standard bupivacaine 
period) 
 
3. STUDY METHODS AND PROCEDURES 
 
3.1. Study Treatment/Intervention 
Unless there is a medical contraindication, all patients undergoing colectomies with Fairfax 
Colon and Rectal Surgery, whether open, laparoscopic, hand-assisted laparoscopic, or robotic, 
will receive a preoperative TAP block. Equal volumes of either standard (0.25% bupivacaine) or 
liposomal bupivacaine (133mg in 10mL, diluted with 20mL saline) will be injected into the 
fascial layer between the internal oblique and the transversus abdominis with ultrasound 
guidance, 30mL per side for a total of 60mL. No extra local anesthetic will be injected during or 
at the conclusion of the case. 
 
Patients will be blinded to which drug they received. The Numeric Rating Scale, rating pain on a 
level from 0 (no pain) to 10 (worst pain), will be used to evaluate pain levels in our postoperative 
patients. This scale is already used and recorded into the patient’s electronic chart for routine 
nursing evaluations. These scores would be collected approximately every 4 hours through 
postoperative day four while in hospital. If in the rare occasion patients are discharged prior to 
POD 3 at 1 pm average pain scores per day up to POD 4 will be collected via the follow-up 
telephone call. Though there are not specific blinding procedures for nursing staff, they will not 
be overtly aware of randomization and this should reduce the potential for nursing bias. Our 
standard post-op pain regimen includes the following standing medications: acetaminophen 


 
8 
 
650mg every 6 hours scheduled, ketorolac 15mg every 6 hours for 24 hours, after which it is 
converted to ibuprofen 600mg every 6 hours. As-needed drugs include oxycodone 5-10mg every 
6 hours as needed, or Tramadol 50mg every 6 hours as needed for individuals age 65 or older. 
Two doses of Hydromorphone 0.4 mg are available within the first 24 hours of the operation as 
needed for individuals who feel that this regimen is insufficient. Enhanced recovery protocol is 
followed for diet advancement, with clear liquids being given to the patient on post-op day zero, 
followed by advancement to a low-residue diet after tolerance of clear liquids for two meals. 
Early ambulation, even in the recovery room, is strongly encouraged as standard practice for our 
patients. These regimens, as well as practices regarding post-op IV fluids, Foley catheter 
removal, deep vein thrombosis (DVT) prophylaxis, and lab draws, are standardized across the 
entire practice of colorectal surgeons at Fairfax Colon and Rectal Surgery. 
 
Additionally, a standardized form within the electronic medical record will be provided to the 
nursing staff to facilitate data collection. Total amount of opioids and non-opioid pain 
medications given is also simple to calculate since opioid use is automatically recorded into the 
chart. These would eventually be added together and reported in morphine equivalents (opioid 
medications only). Some data will be prospectively (time during hospital admission and post-
discharge only through postoperative day 4) and all follow-up data will be collected 
retrospectively after 30-days postoperative collected into a secure REDCap database. 
 
Please see the Appendix, Figures 1 and 2 for the study timetable and study procedure flow chart. 
 
3.2. Control Group  
There is no currently research-proven standard of care.  However, as liposomal bupivacaine is a 
newer formulation, we will use the regular bupivacaine group as a control to compare these two 
commonly-used medications. 
 
3.3. Randomization  
We will alternate standard of care between regular and liposomal bupivacaine every 2 months 
(apart from the first cycle of 4 months per drug), therefore patients will be randomized to either 
study group in clusters. By using cluster randomization instead of individual randomization, we 
can better avoid potential nursing bias. Surgical approach (minimally invasive or open surgery) 
might impact opioid consumption postoperatively; therefore, we will stratify based on surgical 
procedures. To achieve stratification, we will perform an interim analysis following each cycle. 
Coordinators, investigators, and statisticians will then determine what type of patient to continue 
to approach for participation in the following cycle. To allow for this analysis, we will build in a 
short enrollment break at the beginning of each period. Additionally, we hope that this break will 
assist in the TAP block type change-over.  Additionally, to adjust for any potential imbalance 
between two study groups in terms of any important clinical factors, propensity score matching 
may be used to select randomized patients to construct two comparable study groups. 
 
3.4. Endpoints/Outcomes Measurements 
 
3.4.1. Primary outcomes. 
The primary end-point is in-hospital postoperative opioid consumption in patients who undergo 
TAP blocks with either liposomal bupivacaine or regular bupivacaine prior to elective 
colectomy. 


 
9 
 
 
3.4.2. Secondary outcomes 
The secondary end-points are differences in pain scores, total pain medication consumption 
(opioid and non-opioid), time to mobilization, time to return of bowel function, length of stay, 
in-hospital antiemetic use, 30-day postoperative complications (infection, small bowel 
obstruction, dehydration, deep vein thrombosis/pulmonary embolism, anastomotic leak, cardiac 
arrest, stroke, sepsis) or mortality, 30-day post-discharge readmissions, and hospitalization costs 
in patients who undergo TAP blocks with either liposomal bupivacaine or regular bupivacaine 
prior to elective colorectal resection. 
 
3.5. Consent/Assent 
Clinical consent for the TAP block procedure itself will be obtained in the preoperative area by 
the anesthesia team, as is the standard practice now. Consent for participation in the study will be 
obtained postoperatively; patients will be approached in the hospital to request the use of their 
data for research purposes. Ample opportunity will be given to ask questions regarding the 
research study. 
 
3.6.  Monitoring Subjects and Criteria for Withdrawal of Subjects from the Study 
In hospital pain scores will be collected approximately every 4 hours until 1 pm on postoperative 
day 4 and entered into the electronic medical record by the nursing staff. Very rarely, patients 
may go home on postoperative day two. We would like to capture data from these patients, as 
this reflects a shorter length of stay. To capture their opioid and other pain medication use, these 
patients would be contacted by a phone call within 96 hours of discharge and will be asked how 
much oral  opioids and other non-opioid pain medications that were  required for pain control in 
the period from discharge until POD 4. A note reflecting the details of this conversation will then 
be entered in to the patient’s electronic medical record. As medications are scanned prior to 
administration, all medications given to a patient in the hospital are automatically entered into 
the system. 
 
Epic electronic medical records and practice office records will be checked up to 30 days 
following discharge to assess for any complications, readmissions, or mortality. 
 
Per our research department standard operating procedures, quality control monitoring will be 
done on a regular basis to ensure data integrity. 
 
Given the completely voluntary nature of participation in the study, all patients have the right to 
refuse participation, or withdraw from the study at any point in time for any reason without 
medical, personal, or financial repercussions. Patients may be withdrawn from the study by 
investigators if they have unforeseen intraoperative complications that necessitate continued 
intubation and sedation following the initial operation (as these patients would not be able to 
report pain scores), if they have an identified non-abdominal pain source, or if they have an 
emergent return to the operating room. 
 
4. STATISTICAL CONSIDERATIONS/DATA ANALYSIS 
 
4.1. Sample Size  


 
10 
 
The power analysis is conducted to detect whether there is a significant difference in the post-
operative opioid consumption between the two groups during the patient’s first three days 
postoperatively. We assume that the two groups have an approximately equal number of subjects 
after randomization and the length of stay equals to 4 such that we can obtain three repeated 
measurements of daily opioid and non-opioid consumption for each patient. Based on the results 
from Hutchins et al, we further assume that the average opioid usage is 18 mg morphine 
equivalents (180 µg fentanyl equivalents in Hutchins et al.) with a standard deviation equal to 13 
mg for the control group and we expect to observe a 30% reduction in the treatment group. With 
an alpha=0.05, a moderate autocorrelation (ρ=0.5) between the different measurements of opioid 
consumptions and a 20% attrition rate, we estimate that 82 patients per group is sufficient to 
achieve 80% power. Given the possible necessity to perform propensity score matching after 
enrollment and data collection to ensure two comparable study groups in terms of key factors, 
10% increase of sample size is proposed resulting in 101 patients in each group and 202 in total. 
  
4.2. Method of Data Analysis 
Patients’ charts will be analyzed and the following variables will be collected prospectively: 
Patient age, gender, BMI, race, presence of pre-existing conditions (smoking, diabetes, renal 
failure, dialysis, cardiac, GI infection, other infection, transplants), site of operation, type of TAP 
block (liposomal versus standard bupivacaine), type of operation (open, laparoscopic, hand-
assisted laparoscopic, robotic), presence of ostomy, pathology (benign/malignant), ASA grade, 
operative time, estimated blood loss, length of stay, daily overall opioid use recorded as 
morphine equivalents, amount  of medications given for pain control (opioid and non-opioid), 
time to first flatus/gas into ostomy bag and/or bowel movement/ostomy output, time to diet 
advancement (clear liquids and then low fiber), time to mobilization, pain scores, 30-day 
complications, 30-day readmissions, and mortality. We would also attempt to determine 
differences in hospitalization costs. Much of this data is already captured in a Research 
Electronic Data Capture (REDCap) database about Fairfax Colon and Rectal patients, which is 
already maintained by Inova.  These data points would be exported to a separate research 
database, where study-specific data would be entered. 
 
Descriptive statistics will be provided for demographic and clinical factors of each group. They 
will also be compared using the appropriate hypothesis testing procedure, t-test for continuous 
variables, Pearson’s χ2 test for categorical variables and rank-based methods if necessary. 
Statistical significance will be evaluated at alpha=0.05. Pain scores will be recorded on the scale 
of 1 to 10 approximately every 4 hours through postoperative day 3. We will calculate the 
average daily pain scores for each patient and then code it as low pain (1-3), medium pain (4-6) 
and severe pain (7-10). A generalized linear mixed effects model for ordinal outcomes will be 
applied to analyze the pain scores under the proportional odds assumption. Both univariate and 
multivariate models will be considered. Estimated odds ratios and 95% confidence intervals will 
be reported. Daily opioid consumption can be considered as a continuous variable, so a linear 
mixed effects model will be applied here. Parameter estimates and the 95% confidence intervals 
for univariate and multivariate models will be presented. Further univariate subgroup analysis 
will be conducted for open and minimally invasive procedures, and multivariate subgroup 
analysis will be implemented if the sample sizes are sufficiently large. Intention-to-treat analysis 
will be performed. 
 
We will perform an interim analysis following each cycle as described in section 3.3.  


 
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4.3. Data Storage 
 
4.3.1. Data Management 
Data will be collected and maintained using Inova’s password-protected REDCap software 
system. Any data exported from REDCap for analysis will be saved on Inova-secured shared 
drives. Some of the data that will be used for this study is already collected for all colorectal 
patients and maintained in a colorectal quality database. Any data points specific to the study 
(study ID, type of TAP block, pain scores, opioid use, time to bowel function/clear liquid 
diet/low fiber diet/mobilization, antiemetic use, and costs) will be recorded in a separate, study-
specific REDCap database. Only approved study personnel will be given access to this database.  
 
4.3.2.  Records Retention 
Study-specific data will be destroyed 3 years after completion of the study, per HIPAA 
regulations. 
 
5. HUMAN SUBJECTS PROTECTION (RISKS, BENEFITS, AND ALTERNATIVES) 
 
5.1. Risks 
Risks to the patient include standard risks associated with the TAP block; these, however, are quite 
rare, and have been published as case reports. Patients would be subject to these risks regardless of 
whether or not they participate in research as both TAP blocks are used as standard of care in this 
practice. There are no published reports describing local anesthetic toxicity after TAP blocks. 
While there are case reports detailing liver lacerations with right-sided TAP blocks, these were 
with landmark-based blocks or due to inadequate needle visualization with ultrasound guidance2. 
Other potential risks include bleeding and infection, but these are also quite rare. As stated 
previously, the anesthesiologists of Fairfax Anesthesiology Associates have a highly standardized 
method for ultrasound-guided TAP block under sterile conditions. Providers are closely mentored 
prior to performing the TAP block independently.  To date, there have been no complications from 
TAP blocks performed at Inova Fairfax Hospital. As nearly all patients receive the TAP block with 
either standard or liposomal bupivacaine as standard of care prior to elective colorectal resection 
with the associates of Fairfax Colon and Rectal Surgery, the risk of participating in this study is 
essentially equivalent to standard treatment.   
 
Participants will also have a risk of potential loss of confidentiality. The risk of potential loss of 
privacy is of low severity and rare probability.  There is also a risk of unknown side effects. 
 
5.2. Benefits  
There may be no direct benefits to patients who participate. The results of this study will benefit 
future patients at our institution and throughout the colorectal surgery field.  
 
5.3.  Alternatives 
Patients may choose not to take part in the study. 
 
5.4. Confidentiality 


 
12 
 
Data will be kept in a secure REDCap research database, accessible only to authorized research 
personnel. The data will be de-identified prior to data analysis, further reducing the risk of 
compromising confidentiality. 
 
6. SUBJECT COMPENSATION   
6.1. Costs 
There are no costs to participants outside of the usual costs that would already be associated with 
undergoing the elective operation. 
 
6.2. Payment  
There will be no payment for participants. 
 
7. ADVERSE EVENT REPORTING  
Adverse events due to TAP blocks are quite rare, as stated above; however, should any 
complications occur as a direct result of the block, these will be reported to the IRB.  These rare 
events include liver lacerations, bleeding, and infection at the injection sites. All other serious 
adverse events will be reported to the IRB (including death, life-threatening events, prolonged 
hospitalizations, disability or permanent damage). Additionally, the following will be reported 
should they occur: inappropriate invasions of privacy, breaches of confidentiality, data loss, or 
data security issues. For adverse event and severe adverse event form see appendix. 
 
8. FUNDING 
This project has not received any funding. 
 
9. CONFLICTS OF INTEREST  
There are no financial or other conflicts of interests to disclose. If any arise, they will be 
immediately recorded and reported to the Inova IRB. 
 
10. FACILITIES AND EQUIPMENT                              
The study will be conducted at Inova Fairfax Hospital and corresponding practice offices. TAP 
blocks are administered in the operating room preoperatively, after induction of anesthesia. 
Ultrasound guidance is used as a standard practice. All equipment is readily available. Patients will 
be admitted to the surgical floor postoperatively and pain scores and opioid use will be collected in 
a standard fashion. Patients will be approached postoperatively regarding consent for use of their 
data for research purposes. 
 
11. OUTSIDE CONSULTANTS/COLLABORATORS   
N/A 
 
12. CONTRACTURAL AGREEMENTS    
N/A 
 
 
13. REFERENCES 
 


 
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1. Rafi AN. Abdominal field block: a new approach via the lumbar triangle. Anaesthesia: 2001; 
56(10):1024-1026. 
2. Young MJ, Gorlin AW, Modest VE, Quirashi SA. Clinical implications of the transversus 
abdominis plane block in adults. Anesthesiol Res Pract 2012: DOI 10.1155/2012/731645. 
3. Rashid A, Gorissen KJ, Ris F, Gosselink MP, Shorthouse JR, Smith AD, Pandit JJ, Lindsey 
I, Crabtree N. No benefit of ultrasound guided transversus abdominis plane (TAP) blocks 
over local anaesthetic wound infiltration in elective laparoscopic colonic surgery; results of a 
double blind randomised controlled trial. Colorectal Dis 2016; DOI:10.1111/codi.13578. 
4. Oh TK, Yim J, Kim J, Eom W, Lee SA, Park SC, Oh JH, Park JW, Park B, and Kim DH. 
Effects of preoperative ultrasound-guided transversus abdominis plane block on pain after 
laparoscopic surgery for colorectal cancer: a double-blind randomized controlled trial. Surg 
Endosc 2017; 31(1):127-134. 
5. Walter CJ, Maxwell-Armstrong C, Pinkney TD, Conaghan PJ, Bedforth N, Gornall CB, 
Acheson AG. A randomised controlled trial of efficacy of ultrasound-guided transversus 
abdominis plane (TAP) block in laparoscopic colorectal surgery. Surg Endosc 2013; 
27(7):2366-72. 
6. Favuzza J, Delaney CP. Outcomes of discharge after elective laparoscopic colorectal surgery 
with transversus abdominis plane blocks and enhanced recovery pathway. J Am Coll Surg 
2013; 217(2)503-6. 
7. Ris F, Findlay JM, Hompes R, Rashid A, Warwick J, Cunningham C, Jones O, Crabtree N, 
Lindsey I. Addition of transversus abdominis plane block to patient controlled analgesia for 
laparoscopic high anterior resection improves analgesia, reduces opioid requirement and 
expedites recovery of bowel function. Ann C Roll Surg Engl 2014; 96(8):579-85. 
8. Pacira Pharmaceuticals. (2017). Exparel. Retrieved from http://http://www.exparel.com. 
9. U.S. Food and Drug Administration. (2015). Exparel (bupivacaine liposome) Injectable 
Suspension Prescribing Information.  Retrieved from 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022496s019lbl.pdf. 
10. Hupfl K. (2016). A retrospective study comparing liposomal bupivacaine versus traditional 
modalities on post-operative length of stay. Presented at Joint Federal Pharmacy Seminar, 
Washington, DC. 
11. Frye, BM, Bravin, LN, Ernest, EP, and Dietz, MJ. (2016, November). Liposomal 
bupivacaine offers no benefit over ropivicaine for multimodal periarticular injection in total 
knee arthroplasty. Poster session presented at American Association of Hip and Knee 
Surgeons annual meeting, Dallas, TX. 
12. Kazarian, GS, Mrkow DB, and Lonner JH. (2016, November). Pericapsular injection with 
free ropivicaine provides equivalent postoperative analgesia as liposomal bupivacaine 
following unicompartmental knee arthroplasty. Poster session presented at American 
Association of Hip and Knee Surgeons annual meeting, Dallas, TX. 
13. Barron KI, Lamvu GM, Schmidt RC, Fist M, Blanton E, Patanwala I. Wound infiltration 
with extended-release versus short-acting bupivacaine before laparoscopic hysterectomy: a 
randomized controlled trial. J Minin Invasive Gynecol 2017; 24(2):286-292. 


 
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14. Morales R, Mentx H, Newall G, Patronella C, Masters O. Use of abdominal field block 
injections with liposomal bupivacaine to control postoperative pain after abdominoplasty. 
Aesthetic Surgery Journal 2013; 3(8)1148-1153. 
15. Haas E, Onel E, Miller H, Ragupathi M, White PF. A double-blind, randomized, active-
controlled study for post-hemorrhoidectomy pain management with liposome bupivacaine, a 
novel local analgesic formulation. Am Surg 2012; 78(5):574-81. 
16. Knudson RA, Dunlavy PW, Franko J, Raman SR, Kraemer SR. Effectiveness of liposomal 
bupivacaine in colorectal surgery: a pragmatic nonsponsored prospective randomized double 
blinded trial in a community hospital. Dis Colon Rectum 2016; 59(9):862-9. 
17. Hutchins JL, Kesha R, Blanco F, Dunn T, Hochhalter R. Ultrasound-guided subcostal 
transversus abdominis plane blocks with liposomal bupivacaine vs non-liposomal 
bupivacaine for postoperative pain control after laparoscopic hand-assisted donor 
nephrectomy: a prospective randomised observer-blinded study. Anaesthesia 2016; 
71(8):930-7. 
18. Stokes AL, Adhikary SD, Quintili A, Puelo FJ, Choi CS, Hollenbeak CS, Messaris E. 
Liposomal bupivacaine use in transversus abdominis plane blocks reduces pain and 
postoperative intravenous opioid requirement after colorectal surgery. Dis Colon Rectum 
2017; 60(2):170-177. 
 
14. APPENDIX 
 
 
 
 
 
 Study procedures flowchart 
 Recruitment and study timeline 
 Numeric Rating Scale (Pain Scores) 
 Adverse event and severe adverse event reporting form 
 
 
 
Figure 1: Study procedures flowchart 
 
 
 


 
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Figure 3: Depiction of the Numerical Rating Scale to assess pain scores.  Patients are asked to 
rate their pain from 0-10, with 0 being no pain and 10 being the worst possible pain.  Image 
source: www.physio-pedia.com/Numeric_Pain_Rating_Scale. 
Figure 2: 
Recruitment and 
study timeline