Post on 21-Aug-2018
transcript
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