Exparel & Regional Anesthesia. Rishi Modi, MD UTMB Dept of Anesthesia TACORA March 2016

Transcription

1 Exparel & Regional Anesthesia Rishi Modi, MD UTMB Dept of Anesthesia TACORA March 2016

2 What is it actually? Liposomal bupivacaine Microscopic spheres Drug delivery mechanism

3 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

4 Pharmacokinetics Peak plasma concentration Time to maximum plasma concentration Terminal elimination half life Primarily hepatic metabolism for the active components Renal excretion

5 Max plasma concentration

6 Max plasma concentration

7 Efficacy Original studies Bunionectomy Hemorrhoidectomy New industry studies Independent studies

8 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 Sep-Oct;40(5):572-82

9 Safety profile Errors in delivery Look alike Similar size Direct administration

10 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

11 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

12 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

13 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 Oct;28(5):593-7

14 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

15 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

16 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 ml Delivered in large depots Case reports and studies of injection into nerve sites

17 Things to consider: Cost Efficacy Availability of other pain control modalities Alternate long acting modalities Dexamethasone Indwelling catheters

18 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: ii. iii. iv. 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: 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 Nov;117(5): 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. vi. vii. viii. ix. 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 Volume 40 - Issue 5 - p 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 Article ID 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 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 Sep-Oct;40(5):572-82