Clinical trial NCT03859635
Conditions: Pain, Postoperative Thoracic Acute Pain
Keywords: acute pain VATS
Sponsor: Indiana University
Start date: 2019-02-07; Completion date: 2022-11-07
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study is comparing the difference between erector spinae block and surgeon infiltration after VATS (Video Assisted Thoracoscopic Surgery). The outcomes measured are pain scores, opioid usage, opioid side effects, and patient satisfaction.We are also also studying the effectiveness of liposomal bupivacaine (EXPAREL) in a block by randomizing patients to both EXPAREL erector spinae block and simple bupivacaine erector spinae block.

Detailed description:
A total of 120 subjects will be randomized by a computer program into three groups (40 per group): The primary investigator will inform the anesthesiologist who will be doing the block as to what group the patients are randomized to. The research staff completing the patients assessments will be blinded to the randomization.

For the LB group (Ultrasound guided LB Erector Spinae Plane Block), patients should receive a total of 10ml 0.25% bupivacaine plus 20ml Exparel® (15ml at T4 and 15ml at T8) For the SB group (Ultrasound guided SB Erector Spinae Plane Block), patients should receive a total of 30ml 0.5% bupivacaine. (15ml at T4 and 15ml at T8) For the SI group (under video guidance) injected by surgeon using 10ml 0.25% bupivacaine plus 20ml Exparel

All the erector spinae plane blocks will be placed preoperatively after sedation, before intubation and prior to surgery. All procedures will be placed under the supervision of the attending anesthesiologist on the acute pain service or the attending anesthesiologist in the operating room.

For the ESP block, an ultrasound probe is used to visualize the ES musculature about 3 cm laterally from the spinous process. In a cephalad-to-caudad direction advance the needle and inject the anesthetic in the interfacial plane deep to the ES muscles. Confirm positioning by visualization of needle tip and elevation of ES muscles off the transverse process with anesthetic injection. Injection will be performed at T4 and T8 level.

Surgeon infiltration is performed intraoperatively under direct thoracoscopic guidance. The intercostal space will be visualized and injected with LB. Typically, T4 through T8 are infiltrated with the anesthetic mixture.

All patients will be placed on ERAS protocol, which is our standard of practice.

Opioid usage after the block will be recorded by a member of the research team. Pain scores at rest and on movement (knee flexion) 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, 48 and 72 hours after the surgery.

All patients will receive a phone call 6 months after surgery for assessment for chronic post-surgical pain. Patients will be assessed by a member of the research team over the phone. They will be assessed on their pain score and narcotic usage by using the Brief Pain Inventory. Study participation will conclude after the 6 month follow questionnaire has been completed.

Arms: arm 1: All the erector spinae plane blocks will be placed preoperatively using Liposomal Buvicaine. All procedures will be placed under the supervision of the attending anesthesiologist on the acute pain service or the attending anesthesiologist in the operating room. arm 2: All the erector spinae plane blocks will be placed preoperatively using Liposomal Buvicaine. All procedures will be placed under the supervision of the attending anesthesiologist on the acute pain service or the attending anesthesiologist in the operating room. arm 3: At the end of the surgery, the surgeon will infiltrate liposomal bupivacaine under thoracoscopic guidance along the intercostal nerves from T4-T8.
Interventions: intervention 1: Liposomal Bupivacaine intervention 2: Bupivacaine, 0.25% intervention 3: Bupivacaine, 0.5%
Intervention descriptions: intervention 1: 20 ml intervention 2: 10 ml intervention 3: 30 ml

Protocol documents:
Prot_SAP_002.pdf: 
Page 1 of 8 
 
Randomized prospective study comparing Exparel Erector  
Spinae Plane Block vs Simple Bupivacaine Erector Spinae Plane 
Block vs Exparel Surgeon Infiltration for postoperative 
analgesia following video-assisted thoracoscopic surgery 
                                 
 
  
  
  
  
Dr. Yar Yeap 
Asst. Prof., Dept. of Anesthesiology, 
Indiana University School of Medicine 
Fesler Hall 204, 1120 South drive, 
Indianapolis, IN 46202-5115 
  
Dr. TJ Soi  
Department of Anesthesiology  
 
Dr. Mimi Ceppa  
Department of Cardiothoracic Surgery  
   
Dr. Thomas Birdas 
Department of Cardiothoracic Surgery 
  
Ben Vickery  
Medical Student, Indiana University School of Medicine  
 
V.4 2-28-19 
  
  
  
  
  
  
 
 
 
 
 


Page 2 of 8 
 
 
 
 
Table of Contents: 
Study Schema 
1.0        Background 
2.0        Rationale and Specific Aims 
3.0        Inclusion/Exclusion Criteria 
4.0        Enrollment/Randomization 
5.0        Study Procedures 
6.0        Reporting of Adverse Events or Unanticipated Problems 
Involving Risk to Participants or Others 
7.0        Study Withdrawal/Discontinuation 
8.0        Statistical Considerations 
9.0        Privacy/Confidentiality Issues 
10.0    Follow-up and Record Retention 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 


Page 3 of 8 
 
 
 
 
 
 
1.0           Background 
  
Video-assisted thoracic surgery (VATS) is being performed more frequently due to its less invasive 
nature, decreased postoperative pain, and shortened post-operative hospital stay. However, VATS 
procedure still results in significant postoperative pain and the ideal analgesic for postoperative 
pain control following VATS remains unclear. Many modalities for pain control have been 
addressed in the literature: NSAIDs, opioids, epidurals, paravertebral blocks, and surgeon 
infiltration (1, 2). These have been used to manage the significant pain experienced post-VATS with 
varying degrees of success. However, the ideal analgesic regimen for postoperative pain from VATS 
procedures remains to be codified and changes based on provider preference. The purpose of this 
study is to determine the effectiveness of Erector Spinae Plane Block (ESP) versus surgeon 
infiltration for postoperative analgesic control after VATS. 
 
Erector Spinae Plane block was first described by Forero in 2016. This block has shown promise in 
relieving neuropathic pain and in providing analgesic coverage in laparoscopic cholecystectomy, 
mastectomy, and thoracic surgeries (3-7). This block can be thought of as a modified paravertebral 
block, and shows promise of increased safety compared to the paravertebral block. This is due to 
the unique anatomical approach that allows for anesthetic infiltration of the dorsal rami without 
the risk of needle insertion into the paravertebral space (6). The improved safety of this approach 
could allow this block to be used on higher risk patients, like those who present with 
coagulopathies.  
 
Another common method of managing postoperative VATS pain is through surgeon infiltration of 
the intercostal space with local anesthetic. To perform infiltration, surgeons inject the anesthetic 
with direct visualization of the intercostal space, providing targeted analgesic coverage to the 
affected area (8). Some drawbacks to this process are the relatively short duration of action of the 
block, and the requirement of the surgeon to inject all affected intercostal spaces to achieve the 
desired dermatomal block(1, 2). 
 
Exparel, a liposomal formulation of bupivacaine (LB), has shown significant promise in providing 
extended analgesic coverage in the postoperative period. Due to its extended release format, LB can 
provide analgesia coverage for up to 72 hours postoperatively when compared to normal saline and 
has been suggested to reduce postoperative opioid use as well (9). It has provided effective 
analgesia in total knee arthroplasty and hip arthroplasty and has shown promise in open and 
laparoscopic colectomy (10-12). However, there are also studies showing that LB might not be 
superior to standard bupivacaine (SB) in terms of duration of analgesia (13-15). In order to 
compare the duration of action of both form of bupivacaine, we’ll randomized the ESP group to both 
LB group and SB group.  


Page 4 of 8 
 
 
Our hypothesis is that ESP block is superior to surgeon infiltration for pain scores, and LB will be 
superior to SB for ESP block duration of action.  
 
2.0          Rationale and Specific Aims 
  
The specific aim of the study is to compare the difference between the ESP block and surgeon 
infiltration in achieving the following: 
1. Improved postoperative pain scores 
2. Decreased opioid requirements 
3. Improved patient satisfaction scores 
4. Decreased opioid side effects (Nausea, sedation, ileus, urinary retention, respiratory 
depression) 
 
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, 48, and 72 hours. We will also measure postoperative nausea and sedation 
scores at 1, 24, 48, and 72 hours. We will measure time to first flatus, incidence of urinary retention, 
incidence of respiratory depression, and time to discharge. 
 
All patients will receive a phone survey 6 months after surgery to assess for pain and quality of life. 
  
3.0           Inclusion/Exclusion Criteria 
  
Inclusion criteria: 
● Pt undergoing VATS including but not limited to wedge or lobectomy at Indiana University 
Hospital,  
● ASA 1,2,3 or 4 
● Age 18 or older, male or female 
● Desires regional anesthesia for postoperative pain control 
  
Exclusion criteria: 
● Any contraindication for Erector Spinae Plane block 
● History of substance abuse in the past 6 months which would include heroin, marijuana or 
any other illegal street drugs  
● Patient staying intubated after surgery 
● Patient (home dose) taking more than 30mg PO morphine equivalent per day 
● Known allergy or other contraindications to the study medications, which include dilaudid 
and bupivacaine. 


Page 5 of 8 
 
● Pts. scheduled for a pleurodesis, decortication or esophagectomy at Indiana University 
Hospital 
● BMI greater than 40.0. 
 
4.0            Enrollment/Randomization 
  
All VATS cases scheduled by thoracic surgeons at IU Health University Hospital will be identified. 
The subjects will be contacted initially face-to-face by either Dr. Ceppa or Dr. Birdas in their clinics 
prior to their scheduled surgery date.  They will be given a copy of the consent and authorization 
form explaining this study.  The subjects will again be contacted face to face in POCU on the day of 
surgery and the study will be explained in detail and all questions will be answered.  If participation 
is agreed, written consent will be taken and a signed copy of both the authorization and consent 
will be given to the participant. 
A total of 120 subjects will be randomized by the computer program Research Randomizer into 
three groups (40 per group):  The primary investigator will inform the anesthesiologist who will be 
doing the block as to what group the patients are randomized to.  The research staff completing the 
patients assessments will be the only person blinded to the randomization.    
 
1. Ultrasound guided LB Erector Spinae Plane Block with 20ml of Exparel and 10ml 0.25% 
bupivacaine 
2. Ultrasound guided SB Erector Spinae Plane Block with 30ml 0.5% bupivacaine 
3. Surgeon Infiltration under video guidance with 20ml of Exparel and 10ml of 0.25% 
bupivacaine 
 
 
5.0           Study Procedures 
  
All the erector spinae plane blocks will be placed preoperatively after sedation, before intubation 
and prior to surgery.  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 or the attending anesthesiologist in the VATS room. 
 
To perform the ESP block, an ultrasound probe is used to visualize the ES musculature about 3 cm 
laterally from the T5 spinous process. In a cephalad-to-caudad direction advance the needle and 
inject the anesthetic in the interfacial plane deep to the ES muscles. Confirm positioning by 
visualization of needle tip and elevation of ES muscles off the transverse process with anesthetic 
injection. Surgeon infiltration is performed intraoperatively under direct thoracoscopic guidance. 
The intercostal space will be visualized and injected with LB.  Typically, T4 through T8 are 
infiltrated with 2-3mL of the anesthetic mixture. 
 
All patients will receive 1gm of acetaminophen and 600mg of gabapentin preoperatively. Patients 
above 70yo will receive 300mg of gabapentin. General anesthesia will be induced in the operating 
room and the patient will be placed in the lateral position for the VATS procedure.  All patients will 


Page 6 of 8 
 
receive intraoperative lidocaine and ketamine which is used to decrease opioid use after surgery 
and is being used as part of ERAS protocol. The patients will be intubated with dual lumen 
endotracheal tubes and placed on one-lung ventilation for the procedure. All patients will receive 
intravenous patient-controlled analgesia (PCA hydromorphone) post-operatively for breakthrough 
pain. They will also be scheduled on PO acetaminophen. PO oxycodone PRN will be started on POD 
1 once patients tolerate diet. 
 
Opioid usage at 1,24,48,72 hours after the block will be recorded by a member of the research team. 
Pain scores at rest and on movement (knee flexion) 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, 48 and 72 hours after the epidural or PVB. 
Patients will be encouraged to ambulate on postoperative day 1 under supervision. 
 
All patients will receive a phone call 6 months after surgery for assessment for chronic post-
surgical pain.  Patients will be assessed by a member of the research team over the phone. They will 
be assessed on their pain score and narcotic usage by using the Brief Pain Inventory. Study 
participation will conclude after the 6 month follow questionnaire has been completed. 
  
6.0           Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
  
Patients will be monitored by the primary team during the postoperative period which is after 
surgery, through hours, 24, 48, and 72.  We will also follow up in 6 months with a telephone call to 
complete a questionnaire which will conclude all study participation.  Any adverse events or 
unanticipated problems that are reported to the acute pain anesthesia resident who is not listed on 
the study will contact the Principal investigator or one of the study personnel and all events will be 
addressed immediately. All adverse events or unanticipated problems that meet the criteria for 
prompt reporting will be reported to the IRB within 5 business days. 
  
7.0           Study Withdrawal/Discontinuation 
  
The patient can withdraw from the study at any time by contacting the research team or acute pain 
anesthesia resident.  
  
8.0           Statistical Considerations 
  
Primary outcome: VAS score at 24 and 48 hours 
Primary Research Hypothesis: ESP will provide lower pain scores compared to surgeon infiltration 
and ESP with LB will provide longer pain control than ESP with SB. 
 
Secondary outcomes: Opioid usage after 1, 24, 48 and 72 hours. Pain scores using VAS at rest and 
on movement at 1, 24, 48 and 72 hours. Patient satisfaction scores at 24 and 48 hours. Nausea 


Page 7 of 8 
 
scores at 1, 24, 48 and 72 hours. Sedation scores at 1, 24, 48 and 72 hours. Time to first bowel 
movement, incidence of urinary retention, and incidence of respiratory depression will be recorded 
as well. 
 
Secondary Research Hypotheses: ESP blocks will show improved pain control, improved patient 
satisfaction scores, and decreased nausea and sedation scores compared to surgeon infiltration.  
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 three 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. 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 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 91% power be able to detect a 
60% decrease in VAS score between any two groups, assuming two-sided tests each conducted at a 
5% significance level. 
  
9.0           Privacy/Confidentiality Issues 
  
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 and Record Retention 
  
The study will start in late 2018 and will end when a sample size of 120 subjects is achieved. The 
estimated time frame to enroll 120 study subjects is 24 months. After 120 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. 
 


Page 8 of 8 
 
 
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