Transcript Exparel

Exparel: A local liposomal analgesia
injection
The effect of Exparel in total knee arthroplasty
Kimberly A. Mackey, MPAS, PA-C, Dania Bach, MS, PA-C , Deborah Canet, DPT, NCS
Norwalk Hospital/Yale Physician Assistant Surgical Residency,
Department of Surgery at Norwalk Hospital, Yale School of Medicine
Objectives
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Background of Exparel injection
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•
Exparel’s role in pain control postoperatively
Exparel at Norwalk Hospital
•
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Implementation of Exparel in our total knee arthroplasty population
Exploration of data
• A group of patients who received Exparel in comparison to a group of
patients who received the traditional local cocktail injection
Exparel: Background
Exparel: the Basics
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A local, long-acting bupivacaine injection to the surgical site
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First and only local analgesia that incorporates time release, patented
technology called DepoFoam
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DepoFoam is a liposome that engulfs bupivacaine without altering their
structure and releases bupivacaine in an extended release mechanism
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This delivery of bupivacaine through a mass (liposome vesicle) is called a
Depot injection
DepoFoam
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Bupivacaine is released throughout
time with the degradation of the lipid
membrane
Exparel: Early Clinical Trials 2011
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2011: Approved by Food & Drug Administration for administration
intraoperatively for postsurgical analgesia
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Effectiveness
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Proven vs. placebo in 2 large clinical trials
A.
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B.
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Soft Tissue
Excisional hemorrhoidectomy
Orthopedic
• Bunionectomy
Safety
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Proven in 21 clinical trials in various surgical procedures
Exparel: Clarified Labeling 2015
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2015: Clarified with Food & Drug Administration labeling for “broad”
indications for surgeries beyond the two initial clinical trials
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Clarified approval in:
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Transversus abdominis plane (TAP) block
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Oral surgery
May administer with plain bupivacaine in the same syringe
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Bupivacaine plain must be less than 50% of the bupivacaine liposomal
dose
Exparel: the Benefits
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Pain reduction 0-24 hours post surgery
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Used to decrease opioid usage in surgical patients from 0- 72 hours
postoperatively
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Low systemic exposure and under cardiac threshold  great safety profile
Exparel & Bupivacaine plain
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Amide local anesthetic
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Weak organic base
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Mechanism of Action:
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Temporarily decreases the permeability of the local neuron membrane
to sodium ions which inhibits nerve impulses
Exparel vs. Bupivacaine plain
Exparel
Bupivacaine
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Pain reduction: 0-24 hours
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Pain reduction: 0- 6-8 hours
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Half-life: 23.8-34.1 hours
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Half life: 3.5 hours
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Duration:
• Local: 24 hours
• Systemic: 96 hours
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Duration: 6-8 hours
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Onset 5 minutes
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Onset 5- 10 minutes
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Time to peak plasma:
• Bunionectomy: 2 hours
• Hemorrhoidectomy: 30 minutes
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Time to peak plasma:
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30- 45 min
Exparel: the Facts
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Indications
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Contraindications
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Obstetrical paracervical block
Not studied
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Administration into the surgical site for postsurgical analgesia
Patients younger than 18 years of age
Cautions
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Hepatic disease
Exparel Dosing
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Available as Exparel 266 mg/mL in 20 mL vial
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Dosing based on covering surgical site, not weight based
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May dilute in up to 280 mL of sterile saline to increase volume
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Bupivacaine plain must be less than 50% of the bupivacaine liposomal
dose
Inject above, below fascia and subcutaneous tissue
Exparel in Total Knee
Arthroplasty
Implementation of Exparel in a multimodal model of pain
management at Norwalk Hospital
Literature Review
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PubMed search:
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“Liposomal bupivacaine in total knee” and “Exparel total knee”
• = 24 studies
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Mixed results recommending for or against Exparel depending on
comparison analgesia agent
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Most research studies compare Exparel to another analgesia, not a placebo
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May account for the discrepancies in results with Exparel clinical trial
Prior Studies
Exparel : Positive
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2015: Exparel vs. Femoral nerve block
(n=80) in TKA
Exparel: Negative
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2014: Exparel vs. Traditional Periarticular
injection (n= 85)
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Femoral nerve block: Ropivacaine,
epinephrine, tetracaine
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Traditional: ropivacaine, epinephrine, and
morphine
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No difference in pain relief
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Exparel provided inferior pain relief
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Exparel group: increased
ambulation, decreased LOS
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2015: Exparel vs. Bupivacaine plain (n=164)
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No difference in pain control
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Exparel $285.00 vs. Bupivacaine plain
$2.80
Current Model of Pain Management
PreOp
• Scheduled
pain
medication
IntraOp
• Anesthesia
• Local analgesia
• Exparel vs.
Traditional
Local
• Nerve block
PostOp
• Scheduled
pain
medication
• PRN pain
medication
Current Model of Pain Management
Multiphase, multimodal pain management model
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Phase I: Preoperative Analgesia
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Scheduled Medication
Phase II: Intraoperative Analgesia
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Anesthesia
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Local analgesia
* Exparel vs. Traditional cocktail
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Nerve block
Phase III: Postoperative Analgesia
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Scheduled Medication
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PRN Medication
Retrospective study
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Purpose
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Study the effect of Exparel vs. traditional local analgesia in total knee
arthroplasty patients on pain control and clinical outcomes
Methodology
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Inclusion criteria
• Patients of surgeon A and surgeon B undergoing total knee
arthroplasty during February 2015- September 2015
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Exclusion criteria
• Severe hepatic disease
Retrospective study
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Methodology
• Non-randomized, age-matched, surgeon-specific study
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Two groups were formed, Group A and Group B
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Surgeon A performed the total knee arthroplasty in Group A
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Surgeon B performed the total knee arthroplasty in Group B
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Group A received Exparel, Group B received traditional local solution
intraoperatively
Methodology
Group A
Group B
Surgeon A
Performed TKA
Surgeon B
Performed TKA
Group A
received
Exparel
Group B
received
traditional local
injection
Study Protocol
Preoperative
Intraoperative
Postoperative
Scheduled Medication
Anesthesia

Spinal
Scheduled Medication
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Celecoxib 200 mg PO daily x
10 days
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Ketorolac 15 mg- 30 mg IV Q
6 Hours x 3 doses
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Acetaminophen 1000 mg IV Q
8 hours x 2 doses
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Acetaminophen 975 mg PO
Q8H until discharge
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Gabapentin 300 mg PO HS
until discharge
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Celecoxib 200 mg PO x 1 dose
Oxycodone 10 mg PO x 1 dose
Gabapentin 300 mg PO x 1
Local analgesia
dose
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Group A: Injectable Liposome
Solution
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Group B: Injectable Traditional
Cocktail Solution
Nerve Block

Adductor canal nerve block
PRN Medication
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Oxycodone IR 5mg PO Q3 H
PRN pain moderate (4-7)
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Oxycodone IR 10mg PO Q3 H
PRN pain severe (8-10)
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Oxycodone IR 5mg PO BID
prior to physical therapy not to
be given 40 minutes of prior
narcotic
Study protocol
•
All patients in the study received
preoperative medications in
AMBI prior to surgery
Preoperative
Scheduled Medication
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
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Celecoxib 200 mg PO x 1 dose
Oxycodone 10 mg PO x 1 dose
Gabapentin 300 mg PO x 1 dose
Study protocol
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All patients in the study received
spinal anesthesia
All patients received adductor
canal nerve block
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Group A was given Exparel
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Group B was given traditional
local cocktail
Intraoperative
Anesthesia

Spinal
Local analgesia
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Group A: Injectable Liposome Solution

Group B: Injectable Traditional Cocktail Solution
Nerve Block

Adductor canal nerve block
Intraoperative: Local Analgesia
Group A: Exparel
Injectable Liposome Solution
Group B: Traditional Cocktail
Injectable Solution
Bupivacaine liposome injectable (266mg/ml) 20 mL Ropivacaine (0.5%) 30 ml
Bupivacaine (0.25%) 50 mL
Lidocaine (0.5%) 20 ml
Ketorolac (30 mg) 1 ml
Total = 70 mL
Total = 51 mL
Postoperative
Study protocol
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All patients in the study received
scheduled and PRN medication
postoperatively
Scheduled Medication

Celecoxib 200 mg PO daily x 10 days

Ketorolac 15 mg- 30 mg IV Q 6 Hours x 3 doses

Acetaminophen 1000 mg IV Q 8 hours x 2 doses

Acetaminophen 975 mg PO Q8H until discharge

Gabapentin 300 mg PO HS until discharge
PRN Medication

Oxycodone IR 5mg PO Q3 H PRN pain moderate
(4-7)

Oxycodone IR 10mg PO Q3 H PRN pain severe (810)

Oxycodone IR 5mg PO BID prior to physical
therapy not to be given 40 minutes of prior
narcotic
Results
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n=104 patients total
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Group A: n=58 patients received Exparel injectable
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Group B: n=46 patients received traditional cocktail injectable
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Age range: 41- 91 years of age
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Pain controlled 83% in Exparel patients; 89% in traditional cocktail patients
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Exparel patients ambulated 6.6 ft farther POD 0 and overall, total distance
was > 50 ft farther than traditional local injection patients
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Length of stay was less in Exparel patients (0.3 days)
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Larger percentage of Exparel patients discharged home vs ECF (74%)
compared to traditional local injection (57%)
Results
N= Patients
Pain well Ambulation
controlled (ft) POD 0
Ambulation
(ft) Total
Length of Discharge
Stay
home
(days)
Group A
Exparel
n= 58
48 or 83% 17.1 ft
330 ft
2.53
days
43 or 74%
Group B
Traditional
n= 46
41 or 89% 10.5 ft
277 ft
2.78
days
26 or 57%
Conclusion
The Bad
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Patients with Exparel reported
their pain to less controlled than
patients receiving the traditional
injectable solution
Exparel is 100 times more
expensive
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Exparel costs $285.00 vs
bupivacaine plain $2.80
The Good
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Exparel patients ambulated a
longer total distance during
hospital stay
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Exparel patients had a shorter
length of hospital stay
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Larger percentage of Exparel
patients were discharged home as
opposed to ECF
Study Follow Up
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In order to run statistical testing, only
Surgeon A patients were investigated
by unpaired t test statistics
Patients who underwent TKA by
Surgeon A prior to the implementation
of Exparel were compared to those
patients receiving Exparel
Pre-Exparel patients received the
traditional local injection (mentioned
earlier) and Post-Exparel patients
received Exparel intraoperatively
Statistical Testing
Length of Stay
Age
Gender
Ambulation Distance
Follow Up Results
Not Statistically Significant Statistically Significant
Value
Length of Stay
Ambulation distance
Pre-Exparel patients
ambulated significantly
greater distance
Age
ROM
Exparel patients had
significantly greater flexion
and extension
Gender
Conclusion: Revisited
The Bad
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Patients with Exparel reported
their pain less controlled than
patients receiving the traditional
injectable solution
Exparel is 100 times more
expensive
•
The Good
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Exparel patients ambulated a longer
total distance during hospital stay
Surgeon A pre-Exparel patients
significantly ambulated a greater
distance
•
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Exparel costs $285.00 vs
bupivacaine plain $2.80
Exparel patients had a shorter length
of hospital stay
•
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Not statistically significant in
surgeon A patient groups
Larger percentage of Exparel patients
were discharged home as opposed to
ECF
Bottom Line on Exparel
Overall Mixed Results
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Literature: Exparel in total knee arthroplasty
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Pain control
• Equivocal
Norwalk Clinical Outcomes
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Marginally improved
• Greater flexion and extension ROM in Exparel group
• Statistically significant
• Decreased length of stay in Exparel group
• Not statistically significant in only surgeon A’s patients
• Exparel patients increased ambulation in comparison study
• Surgeon A pre-Exparel patients ambulated a statistically farther
distance
References
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Bagsby, D.T, Ireland, P.H., & Meneghini, M. ( 2014). Liposomal Bupivacaine Versus
Traditional Periarticular Injection for Pain Control After Total Knee Athroplasty.
Journal of Arthroplasty. (29) 1687-1690
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Halawi, M.J, Grant, S.A., & Bolognesi, M.P. (2015). Multimodal analgesia for total
joint arthroplasty. Orthopedics, 38, 616-625.
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Schroer WC1, Diesfeld PG1, LeMarr AR1, Morton DJ1, Reedy ME1. (2015). Does
Extended-Release Liposomal Bupivacaine Better Control Pain
Than Bupivacaine After Total KneeArthroplasty (TKA)? A Prospective, Randomized
Clinical Trial. J Arthroplasty. 30(9 Suppl):64-7. doi: 10.1016/j.arth.2015.01.059.
Epub 2015 Jun 3.
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Surdam, J.W., Licini D.J, Baynes N.T., & Arce B.R. (2015) The use
of exparel (liposomal bupivacaine) to manage postoperative pain in
unilateral total kneearthroplasty patients. J Arthroplasty. 30(2):325-9. doi:
10.1016/j.arth.2014.09.004.
References
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Vendittoli, P., Makinen, P., Drolet, P., Lavigne, M., Fallaha, M., Guertin, M., &
Varin, F. (2006). A multimodal analgesia protocol for total knee
arthroplasty. Bone & Joint Surgery, 88, 282-289.
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http://www.exparel.com/
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http://www.pacira.com/depofoam-platform.php
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Exparel Picture: http://www.empr.com/news/exparel-injection-nowavailable/article/235659/
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DepoFoam Picture: http://www.exparel.com/