Clinical trial NCT04003987
Conditions: Hysterectomy
Sponsor: Indiana University
Start date: 2019-05-01; Completion date: 2021-03-04
Enrollment: 78 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the difference between two different pain control methods in patients who will be having a hysterectomy surgery. By collecting this data, we aim to show improved postoperative pain scores, decreased opioid needs, and decreased opioid side effects (nausea, sedation, ileus, urinary retention, respiratory depression).

Detailed description:
For the TAP block, the ultrasound probe is placed transverse to the abdominal wall, between the iliac crest and the costal margin. The needle is placed in the plane of the probe and advanced until it is between the internal oblique and the transversus abdominis muscles. Once in the plane, 2 mL of saline is injected to confirm needle position, then the local anesthetic solution is injected. \[10\]

For the ESP block, as mentioned previously, the ultrasound is positioned in a parasagittal fashion, 2-3 inches lateral to the spinous process. This approach visualizes the transverse process. The needle is inserted cranial-to-caudal to make contact with the shadow of the transverse process, with the needle tip deep to the fascial plane of the erector spinae muscle. Injection of saline confirms the location of the needle, and the anesthetic is injected.

All patients will receive PO acetaminophen and PO gabapentin the morning of surgery. Pt. will be placed on PRN oxycodone/acetaminophen (Percocet) postoperatively. PRN IV dilaudid may be given for severe breakthrough pain.

Opioid usage at 1, 24 and 48 hours after the block will be recorded by a member of the research team. Pain scores at rest and on movement will be measured by the investigator using Visual Analog Scale (VAS). Nausea will be measured using a categorical scoring system (none=0; mild=1; moderate=2; severe=3). Sedation scores will also be assessed by a member of the study team using a sedation scale (awake and alert=0; quietly awake=1; asleep but easily roused=2; deep sleep=3). All these parameters will be measured at 1, 24 and 48 hours after the blocks and patients will be encouraged to ambulate on postoperative day 1 under supervision. Their ambulation activity will be recorded.

Arms: arm 1: For the ESP block the ultrasound is positioned in a parasagittal fashion, 2-3 inches lateral to the spinous process. This approach visualizes the transverse process. The needle is inserted cranial-to-caudal to make contact with the shadow of the transverse process, with the needle tip deep to the fascial plane of the erector spinae muscle. Injection of saline confirms the location of the needle, and the anesthetic is injected (40 ml into each side; 20 ml injected at T8 and 20 ml injected at T12) arm 2: For the TAP block, the ultrasound probe is placed transverse to the abdominal wall, between the iliac crest and the costal margin. The needle is placed in the plane of the probe and advanced until it is between the internal oblique and the transversus abdominis muscles. Once in the plane, 2 mL of saline is injected to confirm needle position, then the local anesthetic solution is injected (40 ml into each side; 20 ml injected for subcostal TAP and 20 ml injected for posterior TAP).
Interventions: intervention 1: Liposomal bupivacaine intervention 2: bupivacaine, 0.125%
Intervention descriptions: intervention 1: 20ml intervention 2: 60ml

Protocol documents:
Prot_SAP_000.pdf: 
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Erector Spinae Plane Block Versus Transverse 
Abdominis Plane Block in Laparoscopic Hysterectomy  
 
 
 
Dr. Matthew Warner 
Indiana University Department of Anesthesia 
 
 
Dr. Yar Luan Yeap 
Indiana University Department of Anesthesia 
 
 
David Scofield 
Medical Student, Indiana University School of Medicine 
 
 
Dr. Kelly Kasper 
Indiana University Department of Obstetric and Gynecology 
 
 
 
 
Protocol: Version 4.0    4-23-19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


2 
 
 
 
1.0 Background 
 
Each year, thousands of hysterectomies are performed for various indications including cancer, 
fibroids, endometriosis, and other conditions. Laparoscopic hysterectomy is often complicated 
by post-operative pain, making pain control challenging especially with the use of opioids. 
Improved pain control increases patient satisfaction and may lead to improved postoperative 
course.[1, 2] Our standard of practice at Indiana University Hospital is to perform Transverse 
Abdominis Plane (TAP) block using liposomal bupivacaine (LB) for these patients to help with 
postoperative analgesia. [3] Recent literature suggests that Erector Spinae Plane (ESP) block 
may be a safe and effective alternative for thoracic, extremity, and abdominal surgeries. [4] 
Currently there are numerous case reports supporting use of ESP block [5] but there are not 
prospective randomized controlled trials comparing these 2 blocks to date. . Our study aims to 
compare the efficacy of ESP block and TAP block in laparoscopic hysterectomy. 
 
The ESP block, first described by Forero in 2016, provides regional anesthesia targeting in the 
range of the T2-L1 branches of thoracolumbar nerves.[6] The ultrasound is positioned in a 
parasagittal fashion, lateral to the spinous process, to visualize the transverse process. The needle 
is inserted cranial-to-caudal in plane traversing through the trapezius muscle, the rhomboid 
major muscle, and the erector spinae mucles, aiming to make contact with the transverse process, 
with the needle tip deep to the plane of the erector spinae muscle, which overlies the transverse 
process. Injection of saline confirms the correct location of the needle as determined by cranio-
caudal spread of saline under the erector spinae muscle, “lifting” it off of the transverse process. 
Once the correct location is identified, the local anesthetic is injected. 
 
We plan to use Exparel®, or a liposomal formulation of bupivacaine, as the analgesia for both 
arms of the study. Because Exparel® is in liposomal form, the lipid solubility allows bupivacaine 
to be released over an extended period of time. It is reported to provide long-lasting analgesia for 
up to 72 hours and may result in decreased opioid consumption and shortened hospital stays. [7] 
There is no current standard of practice for local anesthesia in ESP block. LB has good analgesia 
coverage for up to 72 hours postoperative when compared to normal saline and has been 
suggested to reduce postoperative opioid use as well. [8, 9]  
 
2.0 Rational and Specific Aims 
 
Both of the pain control modalities in this study have been used as postoperative analgesia in 
prior studies. The specific aim of this study is to compare the difference between the pain control 
methods in achieving the following:  
 
1. Decreased opioid requirements 
2. Improved postoperative pain scores 
3. Decreased opioid side effects (Nausea, sedation, ileus, urinary retention, respiratory 
depression)  
 


3 
 
The primary endpoint of this study will be VAS pain score. The VAS scores will be taken with 
both rest and movement. 
 
The secondary endpoint includes intravenous opioid consumption and opioid side effects 
(nausea, sedation, ileus, urinary retention, respiratory depression). The IV and PO opioid doses 
will be quantified at 1, 24, and 48 hours. We will also measure postoperative nausea and sedation 
scores at 1, 24 and 48 hours. We will also assess patient satisfaction postoperative at 24 and 48 
hours. We will also measure time to first flatus, incidence of urinary retention, incidence of 
respiratory depression, ambulation activity, and hospital length of stay. 
 
 
3.0 Inclusion/Exclusion 
 
Inclusion criteria: 
 
• Patients undergoing laparoscopic hysterectomy surgery at Indiana University Hospital 
• ASA class 1, 2, 3 or 4 
• Age 18 or older, female 
• Desires Regional anesthesia for postoperative pain control 
 
Exclusion criteria: 
 
• Any contraindication for ESP or TAP block.  
• History of substance abuse in the past 6 months. 
• Patients on more than 30 mg morphine equivalents of opioids. 
• Any physical, mental or medical conditions which in the opinion of the investigators, 
may confound quantifying postoperative pain resulting from surgery. 
• Known allergy or other contraindications to the study medications (Acetaminophen, 
Gabapentin, Bupivacaine). 
• Postoperative intubation. 
• Any BMI greater than 40.0. 
 
4.0 Enrollment/Randomization 
 
All laparoscopic hysterectomy cases scheduled by OBGYN at IU Health University Hospital will 
be identified. Subjects will be contacted face-to-face prior to surgery. They will be informed 
about the study and all questions will be answered.    All patients will undergo a standardized 
enhanced recovery perioperative care pathway designed and agreed upon by the perioperative 
team of anesthesiologists and surgeons. 
 
A total of 80 subjects will be randomized by a computer program into two groups (40 in each 
group): 
 
1. TAP block – placed by ultrasound using 266mg Exparel (20ml) and 60ml of 0.125% 
bupivacaine. 40ml on each side. 20ml injected for subcostal TAP and 20ml injected for 
posterior TAP.  


4 
 
2. ESP block – placed by ultrasound using 266mg Exparel (20ml) and 60ml of 0.125% 
bupivacaine. 40ml on each side. 20ml injected at T8 and 20ml injected at T12 
 
Randomization will be performed using a block randomization of the 2 groups instead of a 
simple 2-group randomization to keep the study groups fairly balanced throughout enrollment. 
The primary investigator will inform the person doing the block as to what group the patients are 
randomized to. Both the patients and the research staff doing assessments will be blinded to the 
randomization.  
 
5.0 Study procedures:  
 
The TAP blocks will be placed intraoperatively after induction, while ESP blocks will be done 
preoperatively. All procedures will be done using sterile technique with masks, hats, and sterile 
gloves. All procedures will be placed under the supervision of the attending anesthesiologist on 
the acute pain service. 
 
For the TAP block, the ultrasound probe is placed transverse to the abdominal wall, between the 
iliac crest and the costal margin. The needle is placed in the plane of the probe and advanced 
until it is between the internal oblique and the transversus abdominis muscles. Once in the plane, 
2 mL of saline is injected to confirm needle position, then the local anesthetic solution is 
injected. [10]  
 
For the ESP block, as mentioned previously, the ultrasound is positioned in a parasagittal 
fashion, 2-3 inches lateral to the spinous process. This approach visualizes the transverse 
process. The needle is inserted cranial-to-caudal to make contact with the shadow of the 
transverse process, with the needle tip deep to the fascial plane of the erector spinae muscle. 
Injection of saline confirms the location of the needle, and the anesthetic is injected. 
 
All patients will receive PO acetaminophen and PO gabapentin the morning of surgery. Pt. will 
be placed on PRN oxycodone/acetaminophen (Percocet) postoperatively. PRN IV dilaudid may 
be given for severe breakthrough pain.  
 
Opioid usage at 1, 24 and 48 hours after the block will be recorded by a member of the research 
team. Pain scores at rest and on movement will be measured by the investigator using Visual 
Analog Scale (VAS). Nausea will be measured using a categorical scoring system (none=0; 
mild=1; moderate=2; severe=3). Sedation scores will also be assessed by a member of the study 
team using a sedation scale (awake and alert=0; quietly awake=1; asleep but easily roused=2; 
deep sleep=3). All these parameters will be measured at 1, 24 and 48 hours after the blocks and 
patients will be encouraged to ambulate on postoperative day 1 under supervision. Their 
ambulation activity will be recorded.  
 
6.0 Reporting of Adverse Events  
 
Patients will be monitored by the primary team during the postoperative period, and any adverse 
events or unanticipated problems such as local anesthetic toxicity or any abdominal injury will 
be reported to the acute pain service and research team. All adverse events or unanticipated 


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problems that meet the criteria for prompt reporting will be reported to the IRB within 5 business 
days. 
 
 
 
7.0 Study withdrawal/DC 
 
The patient can withdraw from the study at any time by contacting the research team or acute 
pain anesthesia resident. In such an event, patient may still have access to all the IV and oral pain 
medications. Anesthesia acute pain team will continue to follow the patient for 24 hours. After 
24 hours, the anesthesia acute pain team will sign off and all further pain management will be 
done by the primary team. 
 
8.0 Statistical consideration 
 
Primary outcome: VAS score at 24 and 48 hours 
 
Primary Research Hypothesis: ESP block will provide lower postoperative pain scores compared 
to TAP block for laparoscopic hysterectomy as measured by VAS scores at 24 and 48 hours  
 
Secondary outcomes: Narcotic usage after 1, 24 and 48 hours. Pain scores using VAS at rest and 
walking at 1, 24 and 48 hours. Nausea scores at 1, 24 and 48 hours. Sedation scores at 1, 24 and 
48 hours. If the patient is discharged within 48 hours, every effort will be made to obtain data 
points. We will also assess patient satisfaction postoperative at 24 and 48 hours. We will also 
measure time to first flatus, incidence of urinary retention, incidence of respiratory depression, 
ambulation activity and hospital length of stay. 
 
 
Secondary Research Hypotheses:  ESP block will show improved patient satisfaction scores and 
decreased nausea and sedation scores compared to TAP block. 
 
Statistical analysis will be performed using a standard statistical program (SAS or SPSS). All 
data will be summarized (means, standard deviations, standard errors, and ranges for continuous 
variables; frequencies and percentages for categorical variables) by group. Demographic data 
will be compared between the four groups using ANOVA or chi-square tests as appropriate. The 
primary outcome, VAS at 24 and 48 hours, will be compared between the groups using repeated 
measures ANOVA; the model will include fixed effects for group, time, and the group by time 
interaction and random effects to allow correlations between the two times and different 
variances for the two times. Pain and satisfaction scores and opioid usage over time will be 
analyzed using repeated measures ANOVA. Nausea and sedation scores will be compared 
between groups at each time point using Mantel-Haenszel chi-square tests for ordered categorical 
data. Time to first flatus will be compared using log-rank survival analysis; incidence of urinary 
retention, incidence of respiratory depression, and ambulation activity will be compared using 
chi-square tests; and hospital length of stay will be compared using Wilcoxon Rank Sum tests. 
Distributions of the continuous variables will be examined, and a transformation of the data (e.g. 
natural logarithm) or nonparametric tests will be used as necessary. A 5% significance level will 


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be used for all comparisons.  
 
Based on prior studies, the coefficient of variation for the VAS score at 24 and 48 hours is 
estimated to be 0.70. With a sample size of 40 per group the study will have 90% power to detect 
a ratio of means of 1.6 for VAS score between any two groups, assuming two-sided tests each 
conducted at a 5% significance level. 
 
 
9.0 Privacy 
 
All study papers containing patient identifiers will be kept in each subjects confidential study file 
accessible to only the research team.  All records will be kept in a locked room in a locked 
cabinet that only authorized staff enters.  Collected data from each enrolled participant will be 
recorded on Redcap, which is a secure web-based data collection tool. Three years after 
completion of the study, all electronic information and paperwork containing patient identifiers 
will be deleted or shredded. 
 
10.0 
Follow-up/record retention 
 
The study will start in middle of 2019 and will end when a sample size of 80 subjects is 
achieved. The estimated time frame to enroll 80 study subjects is 24 months. After 80 subjects 
have been enrolled, the study will be stopped and the data collected will be analyzed using 
statistical methods. 
 
Three years after completion of the study, all study papers with patient identifiers will be 
shredded and only data without any patient identifiers will be retained by the research team for 
an indefinite time. 
 
References:  
 
 
1. 
Shaffer, E.E., et al., Estimating the Effect of Intravenous Acetaminophen for 
Postoperative Pain Management on Length of Stay and Inpatient Hospital Costs. Adv 
Ther, 2017. 33(12): p. 2211-2228. 
2. 
Routman, H.D., et al., Local injection of liposomal bupivacaine combined with 
intravenous dexamethasone reduces postoperative pain and hospital stay after shoulder 
arthroplasty. J Shoulder Elbow Surg, 2017. 26(4): p. 641-647. 
3. 
Bacal, V., et al., Transversus Abdominis Plane Block for Post Hysterectomy Pain: A 
Systematic Review and Meta-Analysis. J Minim Invasive Gynecol, 2018. 
4. 
Tsui, B.C.H., et al., The erector spinae plane (ESP) block: A pooled review of 242 cases. 
J Clin Anesth, 2018. 53: p. 29-34. 
5. 
Petsas, D., et al., Erector spinae plane block for postoperative analgesia in laparoscopic 
cholecystectomy: a case report. J Pain Res, 2018. 11: p. 1983-1990. 


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6. 
Forero, M., et al., The Erector Spinae Plane Block: A Novel Analgesic Technique in 
Thoracic Neuropathic Pain. Reg Anesth Pain Med, 2016. 41(5): p. 621-7. 
7. 
Vyas, K.S., et al., Systematic Review of Liposomal Bupivacaine (Exparel) for 
Postoperative Analgesia. Plast Reconstr Surg, 2016. 138(4): p. 748e-56e. 
8. 
Hadzic, A., et al., Liposome Bupivacaine Femoral Nerve Block for Postsurgical 
Analgesia after Total Knee Arthroplasty. Anesthesiology, 2016. 124(6): p. 1372-83. 
9. 
Wu, Z.Q., et al., Liposome bupivacaine for pain control after total knee arthroplasty: a 
meta-analysis. J Orthop Surg Res, 2016. 11(1): p. 84. 
10. 
Tsai, H.C., et al., Transversus Abdominis Plane Block: An Updated Review of Anatomy 
and Techniques. Biomed Res Int, 2017. 2017: p. 8284363.