1. Bupivacaine Liposome (EXPAREL): Adjunct to Regional Anesthesia
Sallie Poepsel, PhD, MSN, CRNA, APRN
Director, AANA Region IV

2. No Financial interests to disclose

3. OBJECTIVES
Describe the pharmacokinetics and pharmacodynamics of Exparel.
List the indications for use of Exparel in post-op pain management.
Identify the benefits and risks associated with Exparel use.
Using case reports, delineate the post-op pain management outcomes associated with the use of Exparel

4. DepoFoam® Encapsulated Bupivacaine
DepoFoam drug delivery system composed of multivesicular liposomes
Extended release of bupivacaine for long-acting pain relief
Analgesic effect localized to injection site

5. In 2011:…….
2 positive Phase 3, randomized, double-blind, placebo-controlled trials
Demonstrated efficacy in 2 representative acute pain models
1) Hemorrhoidectomy
2) Bunionectomy

6. Clinical Studies: Exparel
Study
Clinical Setting
Region
Nerve Block
322
Thoracotomy
Thoracic
Intercostal
323
TKA
Lower
Femoral

7. Multimodal Management Recommended to Manage Acute Postsurgical Pain
Combines ≥ 2 analgesic agents or techniques that act by different mechanisms to provide better pain relief with fewer opioids
Usually includes systemic analgesics with local anesthetics

8. Post-Op Surgical Pain: What we know
unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
is as subjective and variable as the perception of pain
surgeons interpret and manage pain differently

9. Post-Op Surgical Pain: What we know
the treatment of post-surgical pain varies so greatly
Pharmacological agents remain the mainstay of the management of acute perioperative and postoperative pain
Treatment requires a combination of multiple pharmacotherapies and routes of delivery

10. Bupivacaine Liposome Injectable Suspension

11. Intended Response
single-dose administration into the surgical site to produce postsurgical analgesia
blocks the generation and the conduction of nerve impulses
* increasing the threshold for electrical excitation in
the nerve,
* slowing the propagation of the nerve impulse,
* reducing the rate of rise of the action potential.
Generally, progression of anesthesia is related to the following: diameter, myelination, and conduction velocity of affected nerve fibers

12. Pharmacokinetics
Absorption - The rate of systemic absorption of bupivacaine is dependent upon the total dose of drug administered, the route of administration, and the vascularity of the administration site
Distribution - appear to cross the placenta by passive diffusion
Metabolism - are metabolized primarily in the liver via conjugation with glucuronic acid
Excretion - kidney is the main excretory organ for most local anesthetics and their metabolites

13. Interactions with other Drugs:
EXPAREL should not be admixed with lidocaine or other non- bupivacaine-based local anesthetics.
EXPAREL may be administered after at least 20 minutes or more have elapsed following local administration of lidocaine
Bupivacaine HCl, when injected immediately before or admixed with EXPAREL, may impact the pharmacokinetic and/or physicochemical properties of the drug

14. Side Effects
Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems
changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal
local anesthetics can produce central nervous system stimulation, depression, or both

15. EXPAREL
FDA approved, opioid-free, bupivacaine-based, long-acting local anesthetic
Bupivacaine used for nearly 50 years
WHO essential medication
EXPAREL used more than 3,000x per day via infiltration / field block for safe and effective, long-lasting analgesia
EXPAREL can reduce postsurgical use of opioids
Data support broad nerve block indication

16. DOSAGE & ADMINISTRATION
intended for single-dose administration only.
Recommended dose of EXPAREL based on the following factors:
Size of the surgical site
Volume required to cover the area
Individual patient factors that may impact the safety of an
amide local anesthetic
Maximum dose of 266 mg (20 mL) As general guidance in selecting the proper dosing for the planned surgical

17. INJECTION GUIDELINES
EXPAREL should be injected slowly into soft tissues of the surgical site with frequent aspiration to check for blood and minimize the risk of intravascular injection.
EXPAREL is single-dose administration only.
EXPAREL should be administered with a 25 gauge or larger bore needle.
The maximum dosage of EXPAREL should not exceed 266 mg (20 mL, 1.3% of undiluted drug).
EXPAREL can be administered undiluted or diluted to increase volume up to a final concentration of 0.89 mg/mL (i.e. 1:14 dilution by volume) with normal (0.9%) saline or lactated Ringer’s solution.
Different formulations of bupivacaine are not bioequivalent even if the milligram strength is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to EXPAREL.

18. DOSAGE & ADMINISTRATION
As general guidance in selecting the proper dosing for the planned surgical site:
a) Example bunionectomy
A total of 8 mL (106 mg) was administered
7 mL of EXPAREL infiltrated into the tissues
surrounding the osteotomy, and
1 mL infiltrated into the subcutaneous
b) Example – hemmorhoidectomy
A total of 20 mL (266 mg=13.3mg/ml) of EXPAREL diluted with
10 mL of saline, for a total of 30 mL (8.86 mg/ml), divided into six
5 mL aliquots, injected by visualizing the anal sphincter as a
clock face and slowly infiltrating one aliquot to each of the even
numbers to produce a field block

19. COMPATIBILITY CONSIDERATIONS
The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more.
When a topical antiseptic such as povidone iodine (e.g., Betadine®) is applied, the site should be allowed to dry before EXPAREL is administered into the surgical site.
Bupivacaine HCl administered together with EXPAREL may impact the pharmacokinetic and/or physicochemical properties of EXPAREL, and this effect is concentration dependent.
may cause an immediate release of bupivacaine from EXPAREL if administered together locally.
EXPAREL should not be allowed to come into contact with antiseptics such as povidone iodine in solution
the ratio of the milligram dose of bupivacaine HCl solution to EXPAREL does not exceed 1:2. The toxic effects of these drugs are additive and their administration should be used
with caution

20. Hernia Repair (inguinal)
DRUG
ONSET
PEAK
DURATION
Bupivacaine HCL 100 mg
5 min
0-1 hr 8
Exparel 266 mg
P1: 0-2 hrs.
P2: 12-24
72 hrs.

21. Journal of Pain, Vol. 17, No.2 (February 2016) pp.13-157or
Chou et al. J Pain 2016;17:

22. Application to the Practice Setting
There were studies done on the effect of Exparel on patients Exparel dose demonstrated a significant reduction in pain intensity compared to placebo for up to 24 hours
The findings from these studies would be helpful when applied in practice should help practitioner to properly administer and handle the medication

23. Dosing: (following regional blocks: IS or ankle block)
1) added 10 ml of saline to 20 ml vial (266 mg) Exparel (total of 30 ml = 8.86 mg/ml); 5-10 ml injected each layer from the incision line in a fan fashion) 2) 266 mg (20 ml) diluted with 10 ml; injected 15 ml total (half volume = 133 mg) to (20 ml =177 mg) 3) all tissue injections done before closure

24. Dosing: (for hemorrhoidectomy)
1) added 10 ml of saline to 20 ml vial (266 mg) Exparel
(total of 30 ml (8.86 mg/ml)
2) divided into six 5 mL aliquots -produce a field block
injected in a clockwise fashion by slowly infiltrating one
aliquot to each of the even numbers (in the clock) to a
total of 30 ml (266 mg)

25. CASE REPORTS:Pain Scale (IS Block + Exparel)
PROCEDURE
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
RCR (L)
0.5 1 2
2.5
RCR (R)
1.5-2
1.5
1-1.5

26. CASE REPORTS: Opioids/NSAIDS Use
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
RCR (R)
none
NSAID
Opioid x1
Opioid x1/NSAID

27. Summary Decreases pain Single timepoint
Over time • Multiple surgical models
Simple to use: Single intra-op administration
Easy to inject • Fine gauge needle
Decreases opioids: Amount used & Time to first use
Excellent safety
No need for external device
No long-term impact

28. Summary: con’t
The benefits of Exparel extend well beyond effective pain control
other recovery-related outcomes
opioid burden,
hospital stay
time to rehabilitation,
Collectively impact not only institutional costs, but also patient satisfaction (Pacira, 2015)

29. References
Apfelbaum JL, Chen C, Mehta SS, Gan T. J. (2005, October). Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesthesiology, 103(4): Retrieved from
Arcangelo, V. & Peterson, A. (2013). Pharmacotherapeutics for advanced practice. Philadelphia, PA: Lippincott, Williams, & Wilkins. ISBN • ASA Task Force on Pain Management. (1995). Practice guidelines for acute pain management in the perioperative setting. Anesthesiology, 82(1071). Retrieved from
Brennan, T. J., M.D., Ph.D. (2011, January). Pathophysiology of postoperative pain. Pain. 152(3): S33–S40. Doi: /j.pain Retrieved from: •
Krenzischek, D. A. MAS, RN, CPAN, Dunwoody, C. J., MS, RN-BC, Polomano, R. C. , PhD,RN, FAAN, and Rathmell, J. P., M.D. (2008, February). Pharmacotherapy for acute pain: implications for practice. Journal of PeriAnesthesia Nursing 23(1). Retrieve from science/article/pii/S

30. References
Pacira Pharmaceuticals, Inc. (2014). Prescribing information for Exparel. Retrieved from the Exparel Website: EXPAREL_Prescribing_Information.pdf
Pacira Pharmaceuticals, Inc. (2015). New study finds decreased opioid use, hospital stay and readmission rates with Exparel Following Knee Replacement Surgery. Retrieved from c=220759&p=irol-newsArticle&ID=
Rao, M., M.D. (2006, October). Acute post-operative pain. Indian Journal of Anesthesia (5): 340 – 344. Retrieved from
Yu, S.BS; Szulc, A. MA; Walton, S. L. MD; Bosco III, J.A MD; Iorio, R. M.D. (2015, November) Liposomal Bupivacaine versus femoral nerve block for pain control in total knee arthroplasty. Retrieved from epsAbstractAAHKS.cfm?id=2

31. Questions