Exparel & Regional AnesthesiaRishi Modi, MD

UTMB Dept of Anesthesia

TACORA March 2016

What is it actually?

Liposomal bupivacaine

Microscopic spheres

Drug delivery mechanism

http://pacira.com/products/exparel.php

Mechanism of action

Multi-vesicular microscopic spherical particle

Numerous internal chambers

Separated by single bilayer lipid membranes

Stable at refrigeration temperature

Progressive dissipation in vivo

Pharmacokinetics

Peak plasma concentration

Time to maximum plasma concentration

Terminal elimination half life

Primarily hepatic metabolism for the active components

Renal excretion

Max plasma concentration

http://pacira.com/products/exparel.php

Max plasma concentration

http://pacira.com/products/exparel.php

Efficacy

Original studies

• Bunionectomy

• Hemorrhoidectomy

New industry studies

Independent studies

Safety profile

Mild side effects

Labeled as TEAE (treatment emergent adverse effects)

Nausea, constipation, and emesis

Intravascular injection

Wound healing

Safety and Side Effect Profile of Liposome

Bupivacaine (Exparel) in Peripheral Nerve Blocks

Ilfeld et al.

Reg Anesth Pain Med. 2015 Sep-Oct;40(5):572-82

Safety profile

Errors in delivery

• Look alike

• Similar size

• Direct administration

Uses in regional anesthesia

Obstetrical surgery

• TAP, rectus sheath

Orthopedic surgery

• PNB? Adductor Canal, Femoral?

• Intra-articular, wound infiltration by surgeon

General surgery

• TAP, rectus sheath, subcostal

Breast surgery

• Paravertebral, PECS I & II

Use in peripheral nerve blocks

No evidence of nerve injury following single shot PNB with Exparel

Numerous phase 3 trials in process

Case reports have shown good results

Results are optimistic… but to a certain degree

• Studies have been small, incidence of nerve injury is very low

• No long term studies yet

A 4-Day Peripheral Nerve Block? Liposome Bupivacaine: An Introduction and Update, Brian M. Ilfeld

From ASAHQ.org

Wound infiltration

Epidural administration

Peripheral Nerve Blocks

http://www.asahq.org/resources/publications/newsletter-articles/2014/august-2014/a-4-day-peripheral-nerve-block

Liposomal bupivacaine for regional anesthesia, Uskova A and O’Connor JE

Studies lack adequate power

Appears to be safe

Does not show superior clinical results

Curr Opin Anaesthesiol. 2015 Oct;28(5):593-7

Disadvantages in PNB

Lack of surgical anesthesia

Inferior short term analgesia

Inability to titrate effect

Unclear long term side effects or injury

Animal models show peri-neural granulomatous inflammation

MOST IMPORTANTLY, NOT YET APPROVED FOR PNB

Correct usage in the OR for surgeons

25 gauge or larger needle

Invert to re-suspend solution, do not agitate

Injected in multiple aliquots slowly into deep soft tissue with frequent aspiration

Wait 20 minutes before administering any other local anesthetics into the site

Can use bupivacaine up to a max of 50% of Exparel dose

Additive toxic effects

Usage for Anesthesiologists

Same caution as with other local anesthetics

In case of intravascular injection

Typically in abdominal blocks

• Can be mixed with sterile saline to make 40-80 ml

• Delivered in large depots

Case reports and studies of injection into nerve sites

Things to consider:

Cost

Efficacy

Availability of other pain control modalities

Alternate long acting modalities

• Dexamethasone

• Indwelling catheters

References

i. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double blind, and placebo-controlled trial. Dis Colon Rectum. 2011; 54: 1552-1559.

ii. Bergese SD, Onel E, Morren M, Morganroth J. Bupivacaine extended-release liposome injection exhibits a favorable cardiac safety profile. Reg Anesth Pain Med. 2012; 37: 145-151.

iii. Ilfeld BM, Malhotra N, Furnish TJ, Donohue MC, Madison SJ. Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study. Anesth Analg. 2013 Nov;117(5):1248-56

iv. Rita M. Hadley and Alan P Dine. Where is the Evidence? A Critical Review of Bias in the Reporting of Clinical Data for Exparel: A Liposomal Bupivacaine Formulation. J Clinic Res Bioeth 2014, 5:4

v. http://www.exparel.com/how-to-use/dosing.shtml

vi. Ilfeld, Brian M. MD, MS et al. Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Regional Anesthesia & Pain Medicine: September/October 2015 - Volume 40 - Issue 5 - p 572–582

vii. Brigitte M. Richard. The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs. Journal of Drug delivery. Volume 2012. Article ID 962101

viii. Reet Lawhon, Robert LaCivita, John Fanouse, Dennis Feierman.. Off Label Use of Exparel in an Axillary Block for Prolonged Postoperative Analgesia. OJAnes> Vol.5 No.7, July 2015

ix. https://www.outpatientsurgery.net/outpatient-surgery-news-and-trends/health-care-regulation/fda-nixes-exparel-as-nerve-block--03-04-15

x. Uskova A and O’Connor JE. Liposomal Bupivacaine for Regional Anesthesia. Curr Opin Anaesthesiol.2015 Oct;28(5):593-7

xi. Ilfeld et al. Safety and Side effect profile of Liposomal Bupivacaine in Peripheral Nerve Blocks. Reg Anesth Pain Med. 2015 Sep-Oct;40(5):572-82