Clinical trial NCT03827213
Conditions: Pain
Keywords: shoulder surgery, post operative pain
Sponsor: Montefiore Medical Center
Start date: 2019-01-22; Completion date: 2021-06-01
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators are comparing an indwelling catheter with intermediate duration local anesthetic to a single shot peripheral nerve block with long acting a local anesthetic (Exparel).

Detailed description:
While placing an indwelling nerve catheter can prolong pain control, it can also have drawbacks and complications. While major complications like pneumothorax and hemidiaphragmatic paresis from interscalene continuous peripheral nerve blocks (CPNB) are rare, minor adverse effects associated with CPNBs may be more common. They include infection and anatomical damage to blood vessels and nerves due to the indwelling catheter. In addition, catheters take a significantly longer time to set up and place than single shot blocks, which is important as there is often a rush to block patients and trying to get them into the operating room on time. Furthermore, the needle used for catheter placement is larger than the single shot needles, which creates more discomfort to patients during the nerve block. The catheter itself is taped around the entire sides and back of the patient's neck, which is also uncomfortable for patients. Because of how shallow the interscalene block is, the catheter is often found to be dislodged from operating room positioning, patient transport or movement, which negates the placement of the catheter. An indwelling catheter must also be followed up by the acute pain service team until the catheter is removed.

Exparel, or liposomal bupivacaine, is formulated to release low dose bupivacaine over 96 hours, and was recently approved by the FDA in April 2018 to be used in interscalene blocks. The sustained release of local anesthetic could theoretically act similarly to the continuous infusion of local anesthetic through an indwelling interscalene catheter, and could thus avoid the need for placement of a catheter. Current existing data, although inconclusive, has in some studies shown an equal analgesic effect as catheters. As per pharmacy, the cost of the On-Q pump and the local anesthesia needed for the pump together cost $390 for each indwelling catheter placed, not including the cost of anesthesia and pharmacy supplies and labor. The cost of each 20 mL vial of Exparel is less at $285 and, for a single shot nerve block, would avoid the extra costs and time needed for a catheter placement.

The investigators would like to perform a prospective randomized controlled pilot study to examine the efficacy of single shot interscalene blocks using Exparel versus the traditional interscalene catheter used at our institution. The purpose of the study the investigators are proposing is to determine if single shot interscalene nerve blocks using Exparel can provide equivalent or better analgesia than indwelling interscalene catheter in patients who undergo total shoulder replacement surgery. If so, single shot interscalene nerve blocks with Exparel may serve as a quicker, easier, cheaper, safer, and more comfortable alternative to placing indwelling interscalene catheters.

Arms: arm 1: This group will receive an interscalene nerve block. This will be administered as a single 20mL injection consisting of a mixture of 10mL of Exparel and 10mL of 0.5% bupivacaine hydrochloride. arm 2: This group will receive an indwelling interscalene catheter placed posterior to C5-C6 nerve roots (between the shoulders) and administered 15 mL of 0.5% ropivacaine plain for the block with no superficial cervical block. The "On-Q" pump will be set at a rate of 4 mL/hr.
Interventions: intervention 1: Exparel intervention 2: Indwelling Interscalene Catheter
Intervention descriptions: intervention 1: A shot of long acting local anesthetic for post operative pain management intervention 2: ropivacaine, given through a catheter inserted between the shoulders

Protocol documents:
Prot_SAP_000.pdf: 
Prospective Randomized Control Trail Evaluating Single Shot Exparel versus Indwelling 
Interscalene Catheter for Total Shoulder Replacements- A Pilot Study
Introduction:
Shoulder surgery, especially shoulder replacement surgery, is well known to involve severe 
postoperative pain. Regional anesthesia is often the most effective and safe modality for pain 
control, decreasing opioid consumption and its associated side effects and allowing for earlier 
rehabilitation necessary for improving shoulder surgery outcomes. (1, 2) Better analgesia, 
therefore, can reduce hospital length of stay, decrease costs, and improve overall patient 
satisfaction. For major shoulder surgeries, the interscalene nerve block is a well-recognized and 
efficient procedure for controlling pain. Having a continuous infusion of local anesthetics 
through an indwelling interscalene catheter is the best technique for pain control after shoulder 
surgery. (1) Our standard of care for total shoulder replacement surgeries involves placement of 
an indwelling interscalene catheter that is attached to an On-Q pump, which infuses a low dose 
local anesthetic at a set rate continuously until the catheter is removed usually on a postoperative 
day 2. The continuous infusion of local anesthetic through an indwelling catheter allows for a 
more prolonged nerve block and analgesia as compared to a single shot interscalene nerve block, 
whose analgesic duration depends on the local anesthetic and any additives given at the time of 
the block. 
While placing an indwelling nerve catheter can prolong pain control, it can also have drawbacks 
and complications. While major complications like pneumothorax and hemidiaphragmatic 
paresis from interscalene continuous peripheral nerve blocks (CPNB) are rare, minor adverse 
effects associated with CPNBs may be more common. They include infection and anatomical 
damage to blood vessels and nerves due to the indwelling catheter. (3) In addition, catheters take 
a significantly longer time to set up and place than single shot blocks, which is important as there 
is often a rush to block patients and trying to get them into the operating room on time. 
Furthermore, the needle used for catheter placement is larger than the single shot needles, which 
creates more discomfort to patients during the nerve block. The catheter itself is taped around the 
entire sides and back of the patient’s neck, which is also uncomfortable for patients. Because of 
how shallow the interscalene block is, the catheter is often found to be dislodged from operating 
room positioning, patient transport or movement, which negates the placement of the catheter. 
An indwelling catheter must also be followed up by the acute pain service team until the catheter 
is removed.  
Exparel, or liposomal bupivacaine, is formulated to release low dose bupivacaine over 96 hours, 
and was recently approved by the FDA in April 2018 to be used in interscalene blocks. The 
sustained release of local anesthetic could theoretically act similarly to the continuous infusion of 
local anesthetic through an indwelling interscalene catheter, and could thus avoid the need for 
placement of a catheter. Current existing data, although inconclusive, has in some studies shown 
an equal analgesic effect as catheters. (4) As per pharmacy, the cost of the On-Q pump and the 
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019


local anesthesia needed for the pump together cost $390 for each indwelling catheter placed, not 
including the cost of anesthesia and pharmacy supplies and labor. The cost of each 20 mL vial of 
Exparel is less at $285 and, for a single shot nerve block, would avoid the extra costs and time 
needed for a catheter placement. 
We would like to perform a prospective randomized controlled pilot study to examine the 
efficacy of single shot interscalene blocks using Exparel versus the traditional interscalene 
catheter used at our institution. The purpose of the study we are proposing is to determine if 
single shot interscalene nerve blocks using Exparel can provide equivalent or better analgesia 
than indwelling interscalene catheter in patients who undergo total shoulder replacement surgery. 
If so, single shot interscalene nerve blocks with Exparel may serve as a quicker, easier, cheaper, 
safer, and more comfortable alternative to placing indwelling interscalene catheters. 
Hypothesis:
Single shot interscalene nerve blocks using liposomal bupivacaine provides superior analgesia 
than indwelling interscalene catheters for total shoulder replacements.
Primary Objective:
Patient opioid requirements at 24 hours in morphine equivalents 
Secondary Endpoints:
-Intra-operative opioid requirements (morphine equivalents)
- 48-hour opioid requirements (morphine equivalents)
-Patient pain scores in the PACU
Tertiary Endpoint:
-Hospital length of stay
Design and Methods:
This is a randomized controlled study in patients undergoing total shoulder replacement surgery. 
At our institution, these patients typically receive an indwelling interscalene catheter and 
undergo general anesthesia for the surgery. For this study, patients will be randomized into two 
groups: group 1 will receive an indwelling interscalene catheter, while group 2 will receive a 
single shot interscalene nerve block with liposomal bupivacaine.
Group 1 will receive an indwelling interscalene catheter placed posterior to C5-C6 nerve roots, 
and given 15 mL of 0.5% ropivacaine plain for the block with no superficial cervical block. The 
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019


On-Q pump will be set at a rate of 4 mL/hr. A maximum sedation of 2mg of midazolam and 
100mcg of fentanyl may be used for the block. 
Group 2 will receive a single shot interscalene nerve block using 20 mL of a mixture of 10 mL of 
Exparel and ten mL of 0.5% bupivacaine. A maximum sedation of 2mg of midazolam and 
100mcg of fentanyl may be used for the block.
All nerve blocks and catheter placements will be performed under ultrasound guidance with an 
in-plane technique using a stimiplex needle, without twitch monitor, by a trained expert in the 
regional anesthesiology division. The study medications will be drawn up by the regional 
anesthesiologist performing the block.
All patients will undergo general anesthesia and receive the same intraoperative and 
postoperative analgesic regimen. Intraoperatively, patients may receive 100mcg of fentanyl for 
induction, 0.35mg/kg of ketamine before incision, 1g of IV acetaminophen if no contraindication 
and maximum of 2mg of hydromorphone. Postoperatively, patients will receive a 
hydromorphone PCA set at 0.2mg with a lockout of 6 min and no basal dose. Patients will also 
be ordered for 650mg acetaminophen every 6 hrs standing if no contraindication. To clarify, the 
study procedure will be done in addition to standard of care.
The consents will be available and given to patients by IRB approved personnel when they come 
in for their pre-op evaluation visit. Key personnel will explain the study to patients then. If 
patients would like more time to decide, they make take the consent home with them and have 
until day of surgery to sign and agree.
Inclusion Criteria:
-
ASA 1, 2, and 3
-
Ages 40-74
-
Patients scheduled for total shoulder replacement
Exclusion Criteria:
-
ASA 4 and 5
-
Pre-existing pain disorder
-
Regular consumption of chronic pain medication
-
pregnant women 
-
any medical condition such as a clotting disorder 
-
anatomic abnormality that precludes use of an indwelling scalene catheter
-
BMI >40
-
Patient refusal
-
Pre-existing diabetic neuropathy or Hemoglobin A1c >9
-
Failed block
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019


Randomization:
Subjects will be randomized on the day of the procedure. A 1:1 random allocation sequence will 
be used to assign patients to one of the two groups. Pre-sealed randomization envelopes will be 
opened just before performing the block. A physician or nurse that is not part of data collection 
and not directly involved in the care of the patient will prepare the drug according to the 
randomization allocation. A faculty member not directly involved in the study or patient care 
will maintain the randomization codes. 
In case of emergency, the principal investigator or his designee will be able to obtain the 
randomization key. The IRB and DSMB will be notified of the date, time and reason for 
obtaining randomization key will be recorded
Statistical Analysis: 
In this hypothesis-generating pilot study, we are assuming a large effect size between the groups. 
In our clinical audit, the average amount of opioid used by these patients is 29
12 mg. For the 
±
sample size calculation, we are expecting a 50% difference in opioid consumption between the 
two groups.  Based on a two-sided alpha of 0.05 and Type II error of 20% to achieve a clinically 
significant 50 % difference a total of 24 subjects needed to be studied. In order to accommodate 
the missing cases, we are increasing the sample size to 14 patients per group. 
The primary endpoint of the study, 24-hour opioid requirements is a continuous variable a non-
parametric Wilcoxon rank sum test will be used for the analysis. For all the secondary outcomes 
continues variable, will be analyzed similarly as the primary endpoint and categorical variables 
will be analyzed using chi-square analysis or Fischer’s exact test. All the outcomes will be 
reported with 95% confidence interval. For all analysis, a p-value of 0.05 is considered as 
statistically significant. There will be no interim analysis for this study.  As this is a hypothesis-
generating study with small sample size, all the analysis will be reported as unadjusted. 
Data Management:
All information and patient follow up will be entered into a computer database to be maintained 
by the principal investigator or their designee. Information in the database will be tracked by the 
specific randomization code assigned to each patient, which ultimately corresponds to a 
particular arm of the study.
Risks and Benefits:
Exparel is a sustained-release formulation of bupivacaine and thus has similar safety profile as 
other local anesthetics commonly used for peripheral nerve blockade. It has been used in other 
peripheral nerve blockade without any significant side effect experienced by patients. As with 
any nerve block, potential complications including bleeding, infection, nerve damage and 
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019


damage to surrounding structures, and seizures may occur. However, with the use of ultrasound 
guidance by experienced providers, the overall risk of the procedure and the proposed study 
remains very low. (5, 6) On the other side, the indwelling catheter also has risks such as infection 
and anatomical damage to blood vessels and nerves. 
Data Safety Monitoring Board:
All the serious adverse events will be reported to the DSMB and the continuation of the study 
will be at the discretion of the DSMB and the IRB. The DSMB should meet every 6 months to 
review the status of the research in addition to when a serious adverse event occurs.The DSMB 
will consist of Dr. Naum Shaparin and Dr.John Pope
References:
1. Borgeat, Alain, and Georgios Ekatodramis. "Anaesthesia for shoulder surgery." Best 
Practice & Research Clinical Anaesthesiology 16.2 (2002): 211-225.
2. Dowell, Deborah, Tamara M. Haegerich, and Roger Chou. "CDC guideline for 
prescribing opioids for chronic pain—United States, 2016." Jama 315.15 (2016): 1624-
1645.
3. Wiegel, Martin, et al. "Complications and adverse effects associated with continuous 
peripheral nerve blocks in orthopedic patients." Anesthesia & Analgesia 104.6 (2007): 
1578-1582.
4. Sabesan, Vani J., et al. "A prospective randomized trial to identify the optimal 
postoperative pain management in shoulder arthroplasty: liposomal bupivacaine vs. 
continuous peripheral nerve block." Journal of Shoulder and Elbow Surgery 26.5 (2017): 
e150.
5. Ilfeld, Brian M., et al. "Safety and side effect profile of liposome bupivacaine (Exparel) 
in peripheral nerve blocks." Regional anesthesia and pain medicine 40.5 (2015): 572-
582.
6. Richard, Brigitte M., et al. "The safety of EXPAREL®(bupivacaine liposome injectable 
suspension) administered by peripheral nerve block in rabbits and dogs." Journal of drug 
delivery 2012 (2012).
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019
IRB NUMBER: 2018-9707
IRB APPROVAL DATE: 04/09/2019