A Comparison of Ultrasound Guided Transversus Abdominis Plane Nerve Block Technique Versus Laparoscopic Transversus Abdominis Plane Nerve Block Technique Versus No Block on Postoperative Opioid Consumption After Major Colorectal Surgery
Phase: NA
Conditions: Crohn's Disease, Inflammatory Bowel Disease, Postoperative Pain
Sponsor: Cedars-Sinai Medical Center

1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A Comparison of Ultrasound Guided Transversus 
Abdominis Plane Nerve Block Technique Versus 
Laparoscopic Transversus Abdominis Plane Nerve 
Block Technique Versus Placebo on Postoperative 
Opioid Consumption for Major Colorectal Surgery 
Version Date 11.13.2015 
 
 
 
 
 
 
 
 
 
 
STUDY PROPOSAL 
 

2 
 
 
 
 
PRINCIPLE INVESTIGATOR 
Karen Zaghiyan, M.D.** 
 
CO-INVESTIGATORS  
Philip Fleshner, M.D.** 
 
 
 
 
INSTITUTION 
Cedars-Sinai Medical Center  
8700 Beverly Blvd, Room # 8211 
Los Angeles, California 90048 
**Division of Colorectal Surgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

3 
 
STUDY OBJECTIVES 
 
1. The primary objective of this study is to compare ultrasound-guided block of the 
transversus abdominis plane (TAP) vs. laparoscopic-guided TAP block, versus no TAP 
block on opioid consumption in the first 24 hours following colorectal surgery. 
2. The secondary objective of this study is to assess the impact of these adjunctive regional 
techniques on overall patient satisfaction, postoperative pain scores, length of 
postoperative hospital stay, postoperative ileus, and adverse events directly related or 
unrelated to TAP block in the 30-day postoperative period. 
 
 
BACKGROUND AND SIGNIFICANCE 
 
Postoperative pain can pose significant challenges in the postoperative recovery of patients 
undergoing major colorectal surgery. Traditionally, opioids have played an important role in 
treating postoperative pain.  It is well established that opioids are highly effective in relieving 
pain; however opioids are associated with numerous side effects that include nausea, 
vomiting, constipation, ileus, bladder dysfunction, respiratory depression, pruritus, 
drowsiness, sedation, and allergic reaction. These opioid side effects, which range in severity, 
can significantly interfere with discharge home following colorectal surgery. (1) Significant 
interest exists in the use of local anesthetic based regional anesthesia techniques as a means 
to extend the analgesic window for patients undergoing colorectal surgery (2). Specifically, 
the use of the TAP block as an adjunct in postoperative pain control has been widely reported 
in the anesthesia and colorectal surgery literature (2,3). Historically, the block was performed 
in a blind fashion with relative success and presently the block is typically performed either 
with ultrasound guidance or laparoscopic visualization (2,3). While TAP block has shown to 
be effective in post-operative pain control, the techniques used to place the block have not 
formally been compared. 
 
 
We are purposing a prospective, patient-blinded, randomized study of patients undergoing 
major colorectal surgery to compare TAP block under ultrasound guidance versus 
laparoscopic visualization versus no TAP block. We hypothesize that laparoscopic-guided 
TAP block is non-inferior to ultrasound-guided TAP block with respect to perioperative pain 
control and either technique is superior to no TAP.  In addition we will measure procedural 
time, any adverse events related to the block, overall postoperative analgesic requirement, 
analgesic duration, postoperative pain scores, length of postoperative hospital stay, incidence 
of postoperative ileus, and overall patient satisfaction between the three groups. 
 
 
STUDY DESIGN 

4 
 
 
The proposed study is a patient-blinded, prospective randomized study to compare 
ultrasound-guided block of the TAP versus laparoscopic-guided TAP block versus no TAP 
block in patients undergoing major colorectal surgery. The primary outcome measure is 
analgesic requirement in morphine equivalents in the first 24 hours after surgery. Secondary 
outcome measures include overall postoperative analgesic requirement, postoperative pain 
scores, length of postoperative hospital stay, any adverse events related to TAP block, overall 
perioperative complications in the 30-day postoperative period and overall patient 
satisfaction after major colorectal surgery.   
 
 
All groups will receive general anesthesia as the primary mode of anesthesia. Patients 
randomized to one of two treatment arms will also undergo either ultrasound-guided or 
laparoscopic-guided TAP block in the operating room at the conclusion of the procedure. 
Patients randomized to no TAP will not have a TAP block performed but will receive all 
routine intraoperative and postoperative analgesia as deemed appropriate by the anesthesia 
and primary surgical team.  A standardized preoperative non-opioid pain regimen will be 
utilized. In the recovery room, short acting opioids for breakthrough pain will be available. 
Opioids will also be administered for rescue if need be. All patients will receive postoperative 
intravenous narcotics via patient controlled analgesia (PCA) device.  
 
 
STUDY METHODS 
 
I. Recruitment 
a) Patients of the investigators will be recruited for this study during their preoperative 
outpatient appointments approximately one week before surgery. The study material 
packet containing the HIPAA and the informed consent form will be emailed to the 
patient for review.  Thus the patient will have adequate time to ask questions and 
consider the study prior to scheduled surgery.  
b) The patients will be contacted by one of the study investigators the morning of 
surgery at which time a signed consent will be obtained.  
c) Only patients who have provided their written consent and indicated that they have 
been introduced to the study prior to meeting with the anesthesiologists on the day of 
surgery will be able to participate.  
d) Screening procedures will make sure patients meet all inclusion criteria.  
 
 
II. In the preoperative holding area: 

5 
 
a) An anesthesia investigator assigned to the specific case will assess patients and 
perform a pre-operative anesthesia assessment as per standard protocol at CSMC. 
None of this data will be recorded until written informed consent is obtained. 
b) Patients will provide a detailed medical history including demographic information 
(e.g., age, weight, height, ethnic origin, smoking history, history of motion sickness, 
history of postoperative nausea and vomiting, as well as chronic analgesic usage). 
None of this data will be recorded until written informed consent is obtained. 
c) Written informed consent will be obtained by one of the investigators. 
d) Patients will be randomized in a blinded fashion by study staff to one of the groups 
via online randomization site, sealedenvelope.com, in a 2:2:1 fashion.  
 
Group 1  
n=100 
Ultrasound guided TAP Block 
Group 2  
n=100 
Laparoscopic guided TAP Block 
Group 3 
n=40 
No TAP 
 
III. During the intraoperative period 
 
a) Standard anesthesia monitors will be applied: automatic blood pressure cuff, 
three-lead electrocardiography, capnography, and pulse oximetry will be 
used continuously. 
b) Induction of general gnesthesia will be with propofol 2-3 mg/kg & a non-
depolarizing muscle relaxant (choice will be operator dependent). 
Maintenance of anesthesia will be with an inhalational anesthetic.  
c) The study staff performing randomization will instruct the anesthesiologist 
or surgeon to either block the transversus abdominis plane with ultrasound, 
laparoscopy, or no block.  
d) For the block, a standard weight based dose (bupivacaine 0.25% with 
epinephrine 1:200,000, at a 1ml/kg dose) will be used for both ultrasound-
guided or laparoscopic-guided block.  
e) The block is administered between the costal margin and iliac crest in the 
anterior axillary line at 2 different sites on each side (4 injections total). 
f) For ultrasound-guided TAP block, after the surgeons have completed their 
portion of the procedure, a member of the anesthesia research team will use 
sterile technique to prep the abdomen. The block is then placed bilaterally 
(at 2 different sites on each side of the abdomen) in the anterior axillary line, 
between the costal margin and iliac crest in the intermuscular plane between 
the internal oblique and transversus abdominis muscles using ultrasound 
guidance. 
g) For laparoscopic-guided TAP block, the attending surgeon will perform the 
block at the conclusion of the procedure under laparoscopic guidance. 
Bilateral TAP block will be performed in the anterior axillary line between 
the costal margin and iliac crest. After the needle is passed through the skin, 
it is continued until 2 distinct “pops” are felt, indicating the needle pierced 
each of the 2 fascia layers (external oblique and internal oblique fascia). 

6 
 
After injection of the correct plane, a smooth raised area of fluid covered by 
transversus abdominis muscle is seen with the laparoscope. The 
laparoscopic vision also assures that the preperitoneal plane is not injected 
and that the injection does not go intraperitoneal.  
h) Dose of anesthetics, analgesics, local anesthetics, and IV fluid therapy 
during the operation will be recorded in the anesthesia record as per 
standard procedure.  A copy of the sonographic image will be collected for 
each patient at the conclusion of the block.  
i) Duration of surgery (from skin incision until closure) and anesthesia (from 
induction of spinal until discontinuation of the anesthetic drug) will be 
recorded in the anesthesia record as per standard procedure. 
 
IV.  PACU 
a) Verbal rating scale (VRS) for pain will be assessed by the PACU RN upon arrival 
to recovery room, then every 30min interval until discharge. 
o Requirements for “rescue” analgesic medication will be recorded before 
discharge. 
b) Any adverse events during the perioperative period will also be noted by PACU 
RN. 
 
V. Following completion of surgery (post-operative): 
      a) Anesthesia will be discontinued at skin closure. 
b)   Patients will be transferred to the recovery room after emergence from sedation 
c) Treatment of surgical pain prior to discharge from the recovery room: moderate-to-
severe pain (VRS > 7): hydromorphone, 1-1.5 mg IV, moderate pain (VRS of 4-6): 
hydromorphone 0.5 - 1 mg IV., mild pain (VRS 2-3), hydromorphone 0.1-0.2 mg IV.  
Patient pain control medication will continue with the initial treatment medication for 
all subsequent rescue doses as needed until recovery room discharge. 
d) Patient nausea, vomiting, or retching will be initially treated with ondansetron 4mg 
IV.  Patients unresponsive to ondansetron will receive metoclopramide 10mg IV. 
e) Patient discharge criteria from PACU will include: awake and alert, and has stable 
vital signs. 
 
 
VI.  Patient evaluation during hospital admission: 
• VRS for pain assessment will be utilized to assess pain within the first 72 hours 
postoperatively and pain scores will be recorded in the patient chart by the nursing 
staff as per routine CSMC protocol. The average pain scores will be calculated for 
study analysis.  
• VRS scores along with dose for all opioids will be recorded. 
• Physical signs and symptoms related to the peripheral nerve block (residual sensory 
blockade) will be noted. 

7 
 
• Patient satisfaction with the overall technique will also be queried. 
 
Pain evaluation recorded by nursing staff as per standard CSMC guidelines: 
• At PACU every 30 minutes 
• During admission: 12, 24, 48, and 72 hours postoperatively 
 
Patient satisfaction with analgesia will be assessed at the time of hospital discharge or 
within 30 days postoperatively by telephone using a patient satisfaction survey: 
 
Pain Management Satisfaction Survey 
 
On a scale of 1-5, how satisfied were you with your postoperative pain management? 
 
Very 
Unsatisfied  
Somewhat 
Dissatisfied 
Neutral 
Somewhat 
Satisfied 
Extremely 
Satisfied 
1 
2 
3 
4 
5 
 
 
 
1 = very unsatisfied.  
 
5 = extremely satisfied.  
 
    
 
Statistical Considerations 
The following data will be analyzed:  
 
I. Data to be collected will include the following: 
a. Demographic details (age, gender, ethnicity, height, weight and BMI) 
b. Physical factors (height, weight, body mass index) 
c. American Society of Anesthesiologists Classification  
i. I – Healthy patient 
ii. II – Patient with controlled co-existing disease(s) 
iii. III – Patient with non-controlled co-existing disease(s) 
iv. IV – Patient with co-morbid condition(s) that are a constant threat to 
life 
v. V – Patient not expected to survive surgery 
 
 
 
 

8 
 
Data Analysis 
 
Primary outcome measure:   
With a sample size of 100 in each TAP block arm, a two group 0.025 one-sided t-test will 
have 80% power to reject the null hypothesis that the two groups are not equivalent in 
morphine (mg) use in the first 24 hours after surgery and rule in favor of the alternative 
hypothesis that the mean morphine use in the first 24 hours after surgery is equivalent for 
the two groups or the difference in means (
T - 
S) is 10 or farther from zero in the same 
direction, assuming that the expected difference in means is 0 and the common standard 
deviation is 25.  
 
 
Two group t-test of equivalence in means (equal n's) 
1 
Test significance level,  
 (one-sided) 
  0.025 
Equivalence limit difference, 
0 
   10.000 
Expected difference, 
1 
    0.000 
0 - 
1 
   10.000 
Common standard deviation,  
   25.000 
Effect size,  = |
0 - 
1| /  
    0.400 
Power ( % ) 
     80 
n per group 
 100 
 
Secondary outcome measure:  
To show superiority of TAP to No TAP a two group t-test with a 0.05 two-sided 
significance level will have 88% power to detect the difference between a Control Group 1 
(No TAP block) mean, 
1, of 60 mg morphine use in the first 24 hours after surgery and a 
Group 2 (TAP block) mean, 
2, of 45 mg morphine, a difference in means of 15, assuming 
that the common standard deviation is 25 mg, when the sample sizes in the two groups are 
40 and 100, respectively. 
 
Thus total number of patients to show non-inferiority between ultrasound-guided and 
laparoscopic-guided TAP block, and superiority of either technique to no TAP is 240 
patients. Allowing for a 5% drop out rate (n=12 patients), the total number of patients we 
anticipate to recruit is 252.  
 
 
SUBJECT RECRUITMENT 
 
1. The subjects will be approached regarding the study during their preoperative 
consultation visit. If patient indicates a willingness to participate and meets the inclusion 
criteria and does not meet any exclusion criteria, they will be handed, emailed, or mailed 
a copy of the consent form to read, and the study will be scheduled at least 24 hours after 
they have received the consent form to review. The consent form will detail the purposes, 

9 
 
procedures, possible risks and benefits of the study. The informed consent form will have 
a contact number for the investigators to allow subjects to ask questions prior to the day 
of surgery.  
2. Subjects must give informed consent to participate in the study. 
3. When the patient arrives for the surgery, a study investigator will meet with the patient 
and discuss the procedure in detail in the preoperative holding area, and provide another 
copy of the informed consent for the patient to review and sign.  
4. After the patient has signed informed consent, they will be randomized to one of three 
study arms by the study staff.  
 
 
INCLUSION CRITERIA 
A total of 252 patients undergoing laparoscopic colorectal procedures  
Willingness and ability to sign an informed consent document 
No allergies to anesthetic or analgesic medications 
ASA physical status Class I – III adults of either sex 
Aged 18-90 years  
 
 
EXCLUSION CRITERIA 
Patients who demonstrate any one of the following will be excluded from the study: 
1. Refusal to participate in the study 
2. Age <18 or > 90 years  
3. Contraindications to regional blockage including but not limited to: 
a. Patient refusal to regional blockade 
b. Infection at the site of needle insertion 
c. Systemic infection 
d. Bleeding diathesis or coagulopathy (as diagnosed by history or laboratory 
evaluation) 
 
BENEFITS TO STUDY SUBJECTS 
 
TAP block techniques are well described in patients undergoing colorectal surgery 
procedures and with demonstrable benefit with respect to narcotic sparing pain relief. The 
benefit for our participants will be that these techniques will demonstrate enhanced duration 
of analgesia, reduction in opioid intake and a concomitant reduction in side effects. All of 
this should improve patient satisfaction.  
 
COMPENSATION: There is no compensation for study participants. 
 

10 
 
POTENTIAL RISKS: There are the following risks associated with this prospective 
observational study.  
 
A. Local Anesthetics: Inadvertent intravascular injection with resultant local anesthetic 
toxicity could result. Direct visualization, frequent aspiration and inclusion of 
epinephrine as a marker; make the incidence of this very low. In the setting of an 
inadvertent intravascular injection, Intralipid is readily available and has been shown 
to be very effective in reducing morbidity and mortality from LAST (Local 
Anesthetic Systemic Toxicity). 
B. Transversus abdominis plane block. Inadvertent intravascular injection is a potential 
risk associated with any regional technique. This is seen in less than 0.01% of patients 
and that percentage is further mitigated with direct visualization under ultrasound 
guidance.  
C. Epinephrine 1:200,000 produce a minimal risk of vasoconstriction (it is used as a 
marker to reduce the incidence of inadvertent intravascular injection).  
D. Injection site hematoma, ecchymosis, bleeding. Ultrasound guidance and 
laparoscopic guidance will allow investigators visualization to avoid puncture of 
blood vessels and subsequent hematoma. Patients with known bleeding diathesis or 
those on therapeutic anticoagulation will be excluded from the study. 
E. Injection site infection. Sterile technique will minimize this complication. 
Investigators will monitor the injection site for signs of infection including erythema, 
drainage, pain, tenderness or fluctuance. 
F. Pain at the injection site. Small needles are use to perform the injection and therefore 
minimizing associated pain at the injection site.  
 
MAINTAINANCE OF CONFIDENTIALITY: Patients’ names will not be divulged and 
all data will be coded in the study records. Information gained during the course of the study 
will only be used by the investigators for the purpose of this study and no patient names or 
other identifying data will be used in any future publications.  
 
PROCEDURES TO MAINTAIN CONFIDENTIALITY 
All data will be coded and patient’s name will not be disclosed in any of the study records 
according to standard HIPAA policy.  All the information gained during the course of the 
study will be used by the investigator for the evaluation of the purpose of this study in patients 

11 
 
undergoing outpatient surgery.  No patient names (or other identifying data) will be used in 
any further publication.   
 
DATA ACCURACY AND PROTOCOL COMPLIANCE 
 
1. Obtaining Informed Consent: A study investigator will first insure subject eligibility, and 
upon confirmation of this, obtain informed consent from the subject in an interview. 
Assurance of “informed” consent will be performed by discussing the study with the 
subject, and providing the patient a copy of the consent form. 
 
2. Maintaining Confidentiality: Once enrolled in this study, each participating subject will 
be assigned a unique numerical identifier, with all other identifying information removed. 
Subjects’ names will not be divulged and all data will be coded in the study records. A 
master list of enrolled subjects will be kept in a locked and secure room, in a locked and 
secure building, directly accessible only by the study investigators.  Authorized research 
personnel access to any identifying information will be restricted to the minimal level 
needed for performance of the study. No patient names (or other identifying data) will be 
used in any future publication(s). 
 
3. Quality Control for Data Accuracy:  
a. Subject eligibility: Each potentially eligible subject referred to the study will first 
undergo evaluation by a study investigator regarding whether patient meets 
inclusion criteria and any exclusion criteria. This will be done with direct 
referring physician interview, direct subject interview, and focused medical 
record review. 
b. Subject demographic data and questionnaire: Collected by study investigator 
through direct subject interview and focused medical record review. 
c. Laboratory samples: None will be collected 
 
 
 
REFERENCES 
 
1. White PF. Multimodal analgesia: its role in preventing postoperative pain. 
Curr Opin Investig Drugs. 2008 Jan;9(1):76-82. 
2. Walter CJ, Maxwell-Armstrong C, Pinkney TD, et al. A randomised 
controlled trial of the efficacy of ultrasound-guided transversus abdominis 
plane (TAP) block in laparoscopic colorectal surgery. Surg Endosc (2013) 
27:2366–2372. 
3. 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;217:503e 506.