Transversus Abdominus Plane (TAP) Block Catheters vs Liposomal Bupivacaine for Pain Control After Colorectal Surgery: A Prospective Randomized Control Trial
Phase: PHASE4
Conditions: Colorectal Surgery, TAP Blocks
Sponsor: University of California, Davis

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
Page 1 of 9 
 
Revised: January 31, 2017 
1) Protocol Title 
Transversus abdominus plane (TAP) block catheters vs liposomal bupivacaine 
for pain control after colorectal surgery: A prospective randomized control trial  
Protocol Version Date: 1/31/17 
2) Objectives 
i) Primary: Compare the use of TAP blocks with ropivicaine bolus and 
ropivicaine catheters versus single shot TAP blocks with liposomal 
bupivacaine 
(1) We anticipate superior efficacy and pain control with liposomal 
bupivacaine TAP blocks measured by use of opioids (measured in 
oral morphine equivalents) in the first 48 hours following surgery. 
ii) Secondary: 
(1) Assess the efficacy and safety of TAP blocks for pain control after 
colorectal surgery in a prospective fashion 
(a) Hypothesis: Anticipate satisfactory pain control in both TAP 
block groups for somatic abdominal pain measured as 
proportion of pain scores in the mild range (up to 4 out of 10 
pain documented in nursing notes) 
(b) Anticipate equivalent side effects measured as duration of 
ileus, rash, itching, nausea/vomiting. 
(2) Compare the pharmacological costs and medical utilization costs 
of TAP block catheters versus single shot injection of TAP block 
with liposomal bupivacaine 
(a) Anticipate lower medical utilization costs with single shot 
injection with liposomal bupivacaine TAP blocks  
(b) Measured as acquisition cost of drugs and supplies  
 
3) Background 
 
Pain control after abdominal laparoscopic surgery involves multiple components of 
somatic and visceral pain. Although opioids are commonly used for acute postoperative 
pain control, opioid – induced constipation that can increase the risk of postoperative 
ileus, nausea, and pruritus are significant side effects that may prolong hospital length of 
stay.  Multimodal analgesic regimens have been shown to increase pain control while 
sparing the use of systemic opioids. These have included modalities such as 
acetaminophen, non-steroidal anti-inflammatory drugs, and peripheral nerve blocks.   
 
The transversus abdominus plane block (TAP) is a minimally invasive ultrasound guided 
peripheral nerve block that is helpful in decreasing somatic abdominal pain after surgery 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
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Revised: January 31, 2017 
and decreases opioid consumption while improving pain control. TAP involves local 
anesthetic infiltration between the internal oblique and the transversus abdominis plane in     
which space the terminal branches of the anterior roots of the lower six thoracic and first 
lumbar nerves course.  These nerves innervate the anterolateral abdominal wall.  In 
colorectal surgery patients, TAP have resulted in a decrease in 24-hour morphine 
consumption as well as earlier discharge and return to diet time compared to patient 
controlled analgesia (PCA). 
 
At UC Davis, it is standard practice to place TAP blocks with catheters for adult 
colorectal surgery patients for perioperative pain control. In many cases, the TAP 
catheters will remain in the patient for two days and are removed when the patient’s 
somatic pain is controlled and they able to tolerate oral intake. However, it is resource 
intensive requiring the use of two sterile peripheral nerve catheter kits, two CADD 
infusion pumps, nursing time to replace the ropivicaine infusion cassette every 8-10 
hours, and 30-40 minutes of physician time for block placement with additional physician 
time needed for ongoing catheter management. There is also a risk of catheter – related 
complications including inadvertent dislodgement, catheter infections, and increased 
burden to the patient from the two additional catheters tethered to the patient.  
 
An alternative TAP can be performed using liposomal bupivacaine (Exparel). This is an 
extended release local anesthetic that has been shown to last 48-72 hours and is FDA 
approved for surgical plane infiltration including TAP blocks, as detailed in a 2015 FDA 
letter.  Although the expense of the Exparel is higher than a vial of ropivicaine, it is not 
clear that patients will receive equivalent pain control and satisfaction with one time 
Exparel TAP blocks as compared to TAP catheters with ropivicaine for the first 48-72 
hours.  Further, the costs and medical utilization related to TAP catheters may be greater 
than that of one vial of Exparel used for TAP blocks.  Although there have been smaller 
studies showing the efficacy of Exparel for TAP blocks, there is currently no prospective 
study that evaluates the efficacy of single injection TAP blocks with Exparel compared to 
ropivicaine TAP catheters for colorectal surgery patients.   
 
This study is designed to assess the comparative efficacy and cost of these two 
approaches. Results from this study will be significant to the fields of anesthesiology, 
acute pain management and colorectal surgery.  With this prospective study, we will have 
concrete data on the use of single shot Exparel TAP blocks and TAP catheters to improve 
patient care at UC Davis and educate other institutions. 
 
References: 
Feierman, Dennis E., et al. "Liposomal bupivacaine infiltration into the transversus 
abdominis plane for postsurgical analgesia in open abdominal umbilical hernia repair: 
results from a cohort of 13 patients." Journal of pain research 7 (2014): 477. 
 
McDonnell JG, O’Donnell B, Curley G et al. The analgesic efficacy of transversus 
abdominis plane block after abdominal surgery: a prospective randomized controlled 
trial. Anesth Analg 2007; 104: 193–197. 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
Page 3 of 9 
 
Revised: January 31, 2017 
 
Siddiqui MR, Sajid MS, Uncles DR et al. A meta-analysis on the clinical effectiveness of 
transversus abdominis plane block. J Clin Anesth 2011; 23: 7–14. 
 
Walter, Catherine J., et al. "A randomised controlled trial of the efficacy of ultrasound-
guided transversus abdominis plane (TAP) block in laparoscopic colorectal surgery." 
Surgical endoscopy 27.7 (2013): 2366-2372. 
 
Zafar N, Davies R, Greenslade GL, Dixon AR. The evolution of analgesia in an 
‘accelerated’ recovery programme for resectional laparoscopic colorectal surgery with 
anastomosis. Colorectal Dis 2008; 12: 119–124. 
 
4) Inclusion and Exclusion Criteria 
 
Criteria for inclusion will be patients over 18 years of age presenting for elective 
colorectal surgery with Dr. Linda Farkas, Division of Colorectal Surgery, Department of 
Surgery. 
 
Individuals under 18 years of age or above the age of 90, pregnant women, prisoners and 
patients unable to provide consent, and patients unable to speak English will be excluded. 
If the patient is on systemic anticoagulation and is at an increased risk of hematoma then 
they will be excluded as the block will not be performed.  Patients with an allergy to a 
local anesthetic will also be excluded. 
 
5) Study Timelines 
 
Eligible patients will be approached for research and written informed consent will be 
collected on the day of surgery. TAP block catheters or single shot liposomal bupivacaine 
TAP blocks will be placed in the preoperative holding area, prior to surgery start.  
Intraoperative and post-operative care will be routine at the discretion of the physicians 
caring for the patient.  TAP block catheters are followed by the acute pain service faculty 
until removal of the catheters, typically post operative day two or three.  
 
We anticipate completing our enrollment in 2 years (24 months), with data analysis 
completed within 6 months after the final patient has been enrolled. 
 
6) Study Endpoints 
 
The primary end point will be after enrollment of patients is complete for both the TAP 
catheter group and the liposomal bupivacaine group. Secondary endpoints are the time 
for PACU discharge and discharge from the hospital. 
 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
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Revised: January 31, 2017 
7) Procedures Involved 
 
Individuals will be screened for study inclusion/exclusion criteria in the preoperative 
holding area. Faculty anesthesiologist, resident anesthesiologist or trained research staff 
will approach eligible patients in the preoperative holding area, explain the study, and 
obtain written informed consent. 
 
Consenting patients will be randomized to a study arm (Exparel single injection TAP 
block or TAP block catheter). Randomization will be performed based on a random 
number generator (1 or 2) and after patient is consented. Group 1 will be deemed the 
Exparel single shot group while Group 2 is the TAP catheter group. Both procedures are 
performed by the acute pain service with an anesthesiology faculty member and an 
anesthesiology resident on the rotation that month under direct supervision. When 
patients are enrolled into the study, the TAP block for both arms will be performed in the 
preoperative holding area, prior to induction of general anesthesia. Prior to any 
procedure, a preoperative evaluation is performed, consent is verified, procedural time 
out is performed, and emergency medications are available if there are signs of local 
anesthetic toxicity. For each patient, maximum allowable doses of local anesthetic will be 
calculated as to avoid the risk of any possible local anesthetic overdose.   
 
The Exparel TAP block dose will be provided by inpatient pharmacy and will consist of 
266 mg of Exparel (1.3% in 20cc) diluted to 60 ml total volume with 40 ml of 
preservative free normal saline. An injection of 30 ml of volume will be performed on 
each side, with a total of 60ml for bilateral TAP blocks. Exparel is currently FDA 
approved for surgical site infiltration and the classification of TAP blocks as surgical 
field blocks was specified in a FDA letter in fall 2015. This is the current standard 
dilution and volume used in other academic centers for Exparel TAP blocks. 
 
For those randomized to the TAP catheter group, 30 ml of 0.5% ropivicaine will be 
diluted with an additional 30 ml of preservative free normal saline for a total volume of 
60cc, with 30 ml injected into each side. We will also place peripheral nerve catheters, 
approximately 3-5cm into the TAP space after injection of the ropivicaine solution.  
Catheters will be secured to the skin with tegaderm tape. Infusions will be ordered with 
CADD pumps and will be initiated at a rate of 8 ml/hr of 0.2% ropivicaine on the 
inpatient floor.  
 
 
Postoperatively, patients will be monitored in the PACU per routine care. Patients will be 
ordered a combination of standardized short acting opioids (fentanyl), and long acting 
opioids (hydromorphone) in additional to anti-emetics (ondansetron 4mg IV) for 
administration if needed in the PACU. In the PACU, perioperative nursing staff will dose 
medications accordingly to the EMR orders and the PACU clearance time will be logged 
as well. PACU duration is calculated as the time interval between patient arrival into the 
PACU and when the patient is signed out of the PACU by the PACU anesthesiology 
resident/faculty.   
 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
Page 5 of 9 
 
Revised: January 31, 2017 
Post-PACU hospital course will proceed as is standard of care with PRN pain medication.  
Patient with single shot Exparel TAP blocks will be seen on the inpatient floor for two 
days after the surgery to assess for postoperative pain control. Patients with TAP 
catheters will also be seen daily until the catheters are removed by the acute pain service 
and when the patient is tolerating an oral diet and there are no overt signs of 
postoperative ileus. Standard hospital discharge criteria will be used for both groups. 
 
 
Information will be collected from the patients’ hospital stays, including Ultrasound 
imaging of the patient’s TAP block, intraoperative anesthesia record, the amount of 
opioid use in morphine oral equivalents in the first 6, 12, 18, and 24, 36, and 48 hours 
after surgery, incidence of nausea/vomiting, pain score averages from EMR Epic RN 
Pain data, PACU clearance time and length of hospital stay. 
 
8) Data and/or Specimen Management and Confidentiality 
During the study phase, patient information will be stored electronically via a 
password protected database on the UC Davis OneDrive cloud storage folder.  
Only authorized study staff will have access to the file while access to the UC 
Davis OneDrive folder requires UC Davis login. Patients’ information will be 
stored on a secure database with indirect identifiers, such as patient 1, patient 2, 
etc. There will be a separate password protected document that contains the 
indirect and direct identifiers to match the two. After the study has been closed, 
consents will be maintained for three years, and HIPAA consents for six years, in 
compliance with IRB rules and regulations. Any data obtained from the Electronic 
Medical Record (EMR) will be identified by subject ID only and collected onto 
an encrypted spreadsheet on the PI’s password protected computer.  
Statistical analysis plan & Sample size calculation 
The primary outcome measure will be the between group difference in opioid 
consumption in the first 48 hours surgery. 
We anticipate superior pain control in the Exparel group based on the potential for 
TAP catheter problems such as catheter dislodgement and lack of timely infusion 
refill. A difference in 20% of opioid oral morphine equivalents will be considered 
clinically significant. Prior reports (Carney et al) suggest a difference of 55.3mg ± 
17.6 in the control group versus 26.8mg ± 19.8 in the TAP block group. Using a 
power of 0.8 and p<0.05 as statistically significant yields a sample size of 44 per 
group to show significance. We will enroll 100 to allow for early withdrawal or 
protocol violations, with planned interim analysis at n=20 of each group 
completing the study (40 patients) to allow sample size refinement as needed. 
Data will be analyzed for normal distribution. Normally distributed data will be 
compared using a T-test for the 2 groups; data that is not normally distributed will 
be compared using the Mann Whitney U test. Categorical data will be compared 
by Chi square.     

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
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Revised: January 31, 2017 
All data will be stored online in the secure UC Davis OneDrive folder with 
password protected files. All research staff will have completed HIPAA – related 
training and IRB – related training. 
9) Provisions to Monitor the Data to Ensure the Safety of Subjects 
Patients will be monitored closely in the PACU prior to discharge to the inpatient 
floor for any signs and symptoms of local anesthetic toxicity, abdominal pain, or 
allergic reaction. The dose of local anesthetic given will be calculated to be less 
than the toxic dose level for ropivicaine (2-3mg/kg) and liposomal bupivacaine 
(2-3mg/kg). Patients receiving TAP catheters will be seen daily by the acute pain 
service who will visually inspect the site of insertion and assess the patient for any 
abdominal pain. 
Any adverse events, such as intravascular injection, allergic reaction, or other 
unanticipated event will be assessed for its causative relationship to the TAP 
block by the PI (Dr. Zhou).  
 
If a serious adverse event occurs, it will be reported immediately to the IRB and 
will trigger an immediate suspension in enrollment and a review of the injection 
protocol with the Chiefs of both the Departments of Anesthesiology and 
Colorectal 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.  
Any unexpected adverse events will be documented and reported to the IRB as 
well as study participants. 
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 until study 
completion. Data will be reviewed for any adverse effects from TAP blocks, pain 
scores, opioid consumptions, other additional secondary outcome measures such 
as nausea/vomiting. 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
Page 7 of 9 
 
Revised: January 31, 2017 
10)  Withdrawal of Subjects 
 
Because this is a study comparing a single injection versus a peripheral nerve catheter, 
patients receiving a single injection are able to withdraw voluntarily any time prior to 
the injection. If there was difficulty with visualization of the TAP plane with ultrasound 
due to body habitus, then the patient will be withdrawn from the study. At all instances, 
patient safety will be the primary priority above all over study parameters.  
 
With the TAP catheter group, patients may withdraw voluntarily from the study if they 
wish.  
 
11) Risks to Subjects 
A possible risk is the TAP block not providing adequate pain control postoperatively. 
Patients will have access to routine IV and oral pain medications including opioids, 
acetaminophen, NSAIDS, and other multimodal adjuncts. Complications after TAP 
blocks are rare, and there are no known reports of local anesthetic toxicity after TAP 
block injections. There have been case reports of liver laceration with inadvertent injury 
by the injection needle while performing TAP blocks. There is also one case report of 
catheter placement into the peritoneal cavity, although there was no injury to any organs. 
The likelihood of any needle placement errors is minimized by ultrasound visualization 
of the TAP plane and the needle. Any adverse event is less likely with careful aseptic 
technique, performance of a procedural time-out prior to the block, and careful aspiration 
prior to injection of any local anesthesic. 
 
The use of Exparel has been shown to have no greater incidence of adverse events 
compared to plain bupivacaine based on 10 randomized control trials with 823 subjects 
comparing the two. 
 
Allergic reactions/toxicity from local anesthetics are extremely rare, and symptoms can 
range from itching, swelling, difficulty breathing, abnormal heartbeat, and in extreme 
cases, death. 
 
TAP catheters have an inherent risk of hematoma formation, dislodgement and infection 
due to the nature of having a foreign body catheter in the TAP plane of a patient. 
 
12) Potential Benefits to Subjects 
Patients may have decreased postoperative pain control with either of the TAP 
blocks. They may also have decreased intraoperative opioid use as well as less 
postoperative opioid utilization, which in addition to better pain control may lead 
to less opioid – related side effects including pruritus, decreased incidence of 
opioid related constipation and ileus, nausea and vomiting. 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
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Revised: January 31, 2017 
 
13) Sharing of Results with Subjects 
No additional information will be shared with research subjects 
14) Provisions to Protect the Privacy Interests of Subjects 
 
Patients will be approached about enrolling in this study in the preoperative area. The 
person obtaining consent will be a research team member from Anesthesiology and/or 
Surgery departments.  Patient beds in this area are one bed per room; therefore, the 
conversation will be in private, between the research staff 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 state that refusal to enroll will not result in any penalty, including any 
withholding of pain medication in the future. Post-operatively, patient privacy will be 
protected and only study personal will have access to the encrypted study database with 
patient data. 
 
15) Compensation for Research-Related Injury 
 
There is no specific compensation for study participation. TAP blocks are a billable 
procedure and used routinely for postoperative pain control in colorectal surgery patients. 
Any possible complications related to the procedure will be covered by insurance.  
 
16) Economic Burden to Subjects 
No economic burden to patients as TAP blocks are already planned for these 
patients’ surgical operations. Exparel is FDA approved for this use. UCDMC 
formulary restricts Exparel use and requires IRB approval for this application. 
Within an IRB approved protocol the medication would be billed for as with all 
other medications given to the patient.  There is no additional leave time planned 
for patients and these procedures will decrease the patients’ postoperative pain 
control and may allow them to be discharged sooner. 
17) Drugs or Devices 
 
The study medication, liposomal bupivacaine (Exparel) will be obtained from the 
inpatient pharmacy prior to administration of the TAP block. All anesthesiologists 
performing the TAP block will have had prior education about the proper administration 
and dilution of the Exparel single shot injections.  If the patient is receiving TAP block 
catheters, then the ropivicaine 0.25% medication is obtained from the acute pain block 
cart per protocol by the pain service.  
 
18) ClinicalTrials.gov Registration 
 
Section 1:  NIH Funded Studies 

PROTOCOL TITLE: Transversus abdominus plane (TAP) block catheters vs liposomal 
bupivacaine for pain control after colorectal surgery: A prospective randomized control 
trial  
 
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Revised: January 31, 2017 
If yes to BOTH, the study must be registered on Clinicaltrials.gov. 
Yes  
 
This study is funded by the NIH. (If this study is not funded by NIH, go to Section 
2.) 
 
One or more human subjects will be prospectively assigned to one or more 
interventions (which may include placebo or other control) to evaluate the effects of 
those interventions on health-related biomedical or behavioral outcomes. 
 
Section 2:  Studies subject to FDA jurisdiction 
If yes to ANY the study must be registered on Clinicaltrials.gov. 
Yes 
 
 
This is a prospective clinical study of health outcomes in human subjects that 
compares an intervention with an FDA-regulated device against a control. This is 
not a small clinical trial to determine the feasibility of a device, or a clinical trial to 
test prototype devices where the primary outcome measure relates to feasibility 
and not to health outcomes. 
 
This is a pediatric postmarket surveillance of a device as required under section 
522 of the Federal Food, Drug, and Cosmetic Act. 
 
This is a controlled clinical investigation, other than a phase I clinical 
investigation, of a drug subject to section 505 of the Federal Food, Drug, and 
Cosmetic Act or to section 351 of the Public Health Service Act. 
To view a flowchart describing applicable clinical trials subject to FDA jurisdiction click 
here. 
 
Section 3: Publishing the results 
If yes to BOTH the study must be registered on Clinicaltrials.gov. 
Yes  
 
This study prospectively assigns people or a group of people to an intervention, with 
or without concurrent comparison or control groups, to study the cause-and-effect 
relationship between a health-related intervention and a health outcome. 
 
The PI has access to and control over all the data from the clinical trial and has the 
right to publish the results of the trial and plans to publish the results in a journal 
that follows the ICMJE recommendations.  
This requirement includes studies of behavioral interventions. 
 
Section 4: Registration on Clinicaltrials.gov is not required 
Yes  
 
I have read sections 1-3 above and registration on clinicaltrials.gov is not required 
for this research.