A Pilot Study: A Comparison of Liposomal Bupivacaine to Bupivacaine HCl in Transversus Abdominis Planus Block for Abdominal Gynecologic Surgery
Phase: PHASE3
Conditions: Gynecologic Cancer, Post Operative Pain
Sponsor: Abington Memorial Hospital

 
 
 
 
PROTOCOL 
 
Title:  A Pilot Study: A Comparison of Liposomal Bupivacaine (“Exparel™”) to Bupivacaine HCl in 
Tranversus Abdominis Planus (“TAP”) Block for Abdominal Gynecologic Surgery  
 
Sponsor:   
Mark Shahin, MD,  
 
 
Abington Memorial Hospital, 1 Widener 
 
 
Hanjani Institute for Gynecologic Oncology 
 
 
215-885-0220 
 
Principal Investigator:  Heidi Ching, MD 
 
 
 
Abington Memorial Hospital 
 
 
 
1200 Old York Road Price MOB Suite 109  
 
 
 
215-481-4211 
 
 
 
518-813-0526 
 
The following persons are sub-investigators for this research study:   
Jacqueline Kohl, MD 
Faith Pullinger, MD 
Mitchell Edelson, MD 
Elizabeth Burton, MD 
Joel Sorosky, MD
 
I. Objectives/Purpose 
 
 
The proposed pilot study is evaluating the use of Exparel ™  in an anesthesia protocol for patients 
undergoing major lower abdominal gynecologic surgery. Exparel ™ is a formulation of liposomal 
bupivicaine that is reputed to have a much longer duration of action compares to bupivacaine. 
Exparel™ has been originally demonstrated to be safe and effective in bunionectomy and hemor-
rhoidectomy.  It has recently gained FDA approval for all surgical site infiltration including TAP 
(Transversus Abdominis Planus block)  blocks.  Exparel™ has also been studied in other proce-
dures and demonstrated reduction in opioid use and  median length of stay (LOS).   
 
  
Currently, patients on the gynecologic oncology service undergoing major abdominal surgery are 
receiving a type of regional anesthesia using bupivacaine HCl known as a TAP block as part of 
an effort to decrease narcotic use post-operatively and decrease hospital length of stay. Bupiva-
caine has a known eight to twelve hour duration of action, thus addressing immediate post opera-
tive pain. As Exparel™ is anticipated to have a longer duration of action, the purpose of this 
study is to determine if TAP blocks with Exparel™ have an advantage over standard TAP blocks 
with bupivacaine HCl in reducing length of hospital stay in a randomized controlled trial. Our 
hypothesis is that TAP blocks with Exparel™ will result in reduced length of stay contributing to 
significant hospital cost savings. Secondary outcomes include total narcotic use (hypothesized to 
be reduced) and overall complication rates (hypothesized to remain unchanged).  Given there are 
no published data on the efficacy and safety of using Exparel™ in open gynecologic abdominal 
surgery, this will be a pilot study.  
 
 
 

 
 
II. Background Information:  
 
 
Overview of Clinical Studies 
 
 
 
Comparative efficacy and safety of liposome bupivacaine versus bupivacaine HCl  has been  
  
analysed in order to reduce opioid burden in the post surgical setting.  Specific procedures such as 
inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bun-
ionectomy, have been included in recent studies.  In one of the pooled analysis, liposomal bupi-
vacane has been shown to reduce pain scores at a statistically significant level.  Patients receiving 
liposomal bupivacaine were also less likely to experience opioid related adverse events.  
 
  
The following safety information is derived from Exparel™’s website including prescribing in-
formation and important safety information. Exparel™ is indicated for single-dose administration 
into the surgical site to produce post surgical analgesia.  In clinical trials, the most common ad-
verse reactions following  Exparel™ administration were nausea, constipation and vomiting.  
Other common adverse reactions include pyrexia, dizziness, anemia, hypothension, prurities (in-
cidence between 2% and 10%).  The rare adverse reactions (incidence less than 2%) include, but 
are not limited to, chills, erythema, bradycardia, pain, edema, syncope.  
 
  
Exparel™ has been demonstrated to be safe and effective for procedures such as hemorrhoidec-
tomy and bunionectomy, as well as for surgical site infiltration such as TAP blocks. Exparel™ 
use in open abdominal gynecologic surgery for TAP block has not yet been studied specifically. 
Monitoring of cardiovascular and neurological status, as well as vital signs, should be performed 
before, during and after administration of Exparel.  
 
  
 
III.  Procedures 
  
 
  
Patients undergoing laparotomy will be randomized to either Exparel™ or bupivacaine HCl.  
Randomization will occur through computer generated random assignment. Given the nature of 
the medication itself, bupivacaine and Exparel™ have physical inherent differences after manu-
facture and the anesthesiologist will not be able to be blinded. Patients will be blinded to the type 
of TAP block they receive.    
 
 A. Inclusion and Exclusion of Subjects 
  
Inclusion criteria 
1. 
 TAP blocks placed after the laparotomy incision is closed, but before the patient is 
awake, and placed under ultrasound guidance with correct identification of the 
correct abdominal plane.  
2. 
Consent for TAP block signed by patients preoperatively by anesthesiology  
 
 
 
Exclusion criteria 
1. All pregnant patients 
2. All patients under 18 years of age 
3. minimally invasive surgery such as laparoscopy or robotic assisted laparoscopy  
4. medical contraindications to use of bupivacaine or liposomal bupivacaine such as severe 
hepatic and/or renal disease 
 
 
 
We hope to include 128 subjects in this study in order to reach statistical significance.  Please see 
Appendix 1 for sample size calculations.  
 

 
 
 
 
 
B. Assessment of Efficacy/Measurement  
  
Efficacy will be measured through comparing length of hospital stay, total narcotic use, and com-
plications/adverse effects such as nausea, vomiting, constipation and pruritis.  
 
C. Treatment of Subjects 
  
Subjects will need to provide consent for both the surgery and TAP block provided by an anes-
thesiologist.  Post operatively, narcotic availability will not be withheld. 
 
D. Validity  
 
 
Internal validity will be addressed by randomizing the subjects to avoid selection bias.  Patients 
will also be blinded to the type of TAP block they will receive to eliminate recall bias.  
 
E. Discontinuation of the Study 
  
Study involvement will be discontinued if the subject displays an immediate reaction to the local 
anesthetic, whether bupivacaine or liposomal bupivacaine.  Interim analysis after enrollment of 
first 50 patients will be done and if there is a clear benefit of use of Exparel™ over Bupivacaine, 
the study will be discontinued. 
 
IV. Methods  
 
1. Informed consent will be offered to patients in pre op area and patients will be randomized. 
Charts will be labeled with a card stating bupivacaine, vs  Exparel.  A consent for anesthesia in-
cluding TAP block is signed by patients preoperatively.  
 
2. All TAPs will be placed after the laparotomy incision is closed but before the patient is awake.  
 
3. Anesthesia will place the TAP with Ultrasound. 
 
4. We will typically not open the Exparel before closure of fascia. Once EXPAREL is open it is on-
ly good for 4 hours so should NOT be opened until right before you are ready to use 
 
5. Surgeon will notify anesthesia if the incision is extended above the umbilicus 
 
6. When performing a bilateral TAP with Exparel and the incision is below the umbilicus:  the 20 
ml vial of Exparel, containing 266 mg, will be diluted with 20 ml of 0.25% bupivacaine (contain-
ing 50 mg of bupivacaine) and 20 ml saline (60 ml total). That total volume will be divided into 
two 30 ml syringes, and each will be used (per side) for the TAP blocks. 
 
7. When performing a bilateral TAP with Exparel  and the incision extends above the umbilicus: 
160 ml of saline will be mixed with 20 ml (266 mg) of Exparel for a total volume of 80 ml. Of 
this volume, 40 ml will be passed off to the surgeon for direct infiltration into the supraumbilical 
portion of the incision. The remaining volume (40 ml) will be retained by the anesthesia team. 
That remaining volume will be subdivided into two syringes, and to each syringe will also be 
added 10 ml of 0.25% bupivacaine (25 mg), for a total volume per side of 30 ml, which will be 
used in the TAP blocks. 
 

 
 
8. When performing a bilateral TAP with Bupivicaine 0.25% and the incision is below the umbil 
icus:  30 ml of 0.25% bupivacaine is drawn up and given on each side after identification of 
planes by the anesthesiologist (need 2 vials). 
 
9. When performing a bilateral TAP with Bupivicaine 0.25% and the incision extends above the 
umbilicus: 30 ml of 0.25% bupivacaine is drawn up and given on each side after identification of 
planes by the anesthesiologist (need 2 vials). A 3rd vial of 30 ml 0.25% bupivacaine will be drawn 
up and is directly infiltrated into the surgical site (above and below the fascia prior to closure of 
fascia) extending above the umbilicus by the surgeon.  
 
10. Anesthesia will identify the correct abdominal plane with ultrasound. Normal saline 1-5 ml will 
be used initially, for hydrodissection, to provide confirmation of needle tip position. Once con-
firmed, 5ml per side of 0.25% bupivacaine will be injected into the plane with Exparel to follow. 
This will allow some short term activity of TAP block before Exparel starts to take effect.  In ad-
dition, at the recommendation of the anesthesia, patients in both Exparel and plain bupivacaine 
groups will be given hydromorphone 0.5 mg IV coincident with the performance of the TAP 
block, prior to emergence from anesthesia and extubation.  
 
11. Our goal is to collect information on total opioid usage, length of stay, as well as complications/ 
adverse effects. 
 
 
V. Statistics 
  
Results from the study will be submitted to the department’s statistician for statistical analysis.  
Interim analysis may be performed to assess the efficacy of Exparel™.  
 
VI. Quality Control and Assurance 
  
Every anesthesiologist that will be administering the TAP block in this study will perform the 
TAP block in a controlled fashion under certain guidelines whether using bupivacaine or Expar-
el™.  Every surgeon that is participating as a sub-investigator will be informed of the correct pro-
cedure and protocol.  
 
VII. Ethics 
  
There has been much data showing that TAP block is successful and reduces post operative pain 
using bupivacaine.  The unknown effect of Exparel™ in TAP block for gynecologic surgery, es-
pecially in exploratory laparotomy, is the reason for the study.  Exparel™ is much more costly 
than bupivicaine. If the use of Exparel™ results in significant reduction in length of stay, then 
expenditure for this agent is justifiable. Given that Exparel™ has been used in other types of sur-
geries for post operative pain relief, it is ethical to use Exparel™ in this type of study.  Expar-
el™’s adverse effect profile, which includes nausea, vomiting and pruritis, is acceptable and 
therefore ethical to use in this study.   
 
VIII. Data handling and Record keeping 
1) 
review of charts - resident and attending notes 
2) 
review of medication administration  
3) 
two independent reviewers of charts  
 
IX.  Project Timetable/Flowchart 
 1) February 2016- IRB Submission - Consent/Protocol 

 
 
 2) March 2016 - IRB Resubmission 
 3) June 2016 - IRB Resubmission  
 3) July 2017 - February 2017 data gathering (8 months) 
 4) March 2017 - data analysis  
 
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