Disclosure. Goals: Liposome Bupivacaine (Exparel) 5/12/2016

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1 Liposome Bupivacaine (Exparel) Current Uses and Future Admir Hadzic, MD, Professor of Anesthesiology Director, NAICE (North American Institute for Continuing Education) Director, NYSORA (The New York School of Regional Anesthesia) Consultant, Department of Anesthesiology, Ziekenhuis Oost-Limburg, Genk, Belgium Goals: Catheters Future: Liposome bupivacaine Mechanism of action Current clinical uses Systemic and NeuroToxicity Concerns Local tissue and Neurotoxicity Current research Disclosure Research grants: GSK, Baxter, Pacira Advisor: GE, Sonosite, BD, B Braun, LifeTech Consultant: Pacira Pharmaceuticals Royalty income: BBraun Medical Avenue-V, LLC 1

2 In an ideal world Catheters would be BEST analgesic solution Problems with Catheters? NO Standards? 2

3 Complications? 3

4 Retained catheter with neck abscess after total shoulder replacement Shocker 20 Lean Volunteers US-guided FNB Cath 3 cm beyond tip Ambulate Q 1hr Check Cath Tip by US How many catheters are not in the therapeutic position after 1, 2, 3, 4, 5, 6 hrs? 25% 4

5 ? DepoFoam R Structure 5

6 Current Clinical use FDA Approved? Soft tissue infiltration Local Infiltration into Surgical Site 6

7 DATA? 7

8 Dasta et al., Curr Med Res Opin, 2012; 28, Dasta et al., Curr Med Res Opin, 2012; 28,

9 Dasta et al., Curr Med Res Opin, 2012; 28, LIA Total Knee Replacement Barrington et al., Am J Orth, Click to add title Click to add subtitle 9

10 Infiltration for hemorrhoidectomy (Standard anal block) SURGICAL SITE Hemorrhoidectomy Infiltration for abdominal surgery (TAP infiltration) SURGICAL SITE abdominal wall = CAN DILUTE TO REQUIRED VOLUME Exparel 266mg (20ml) l Exparel 266mg + 20ml NaCl = 40ml solution 0.25% Bupivacaine No mixing with other LA (liposome stability) 10

11 LAST Scare PLASMA LEVEL OF EXPAREL AFTER SOFT TISSUE INJECTION Plasma Bupivacaine HCl Concentration (ng/ml) Exparel 266mg Bupivacaine 100mg CNS Toxicity: 2,500 to 4,000 ng/ml Time, Hours 11

12 Inadvertent IV Injection? IV INJECTION in dogs CNS Toxicity: 2,500 to 4,000 ng/ml 3x Inadvertent IV Injection? Low free bupivacaine exposure ~ 50% remains as intact EXPAREL particles ~45% Bupivacaine associated with lipid fragments ~ 5% Free Bupivacaine Free bupivacaine releases slowly from liposomes after IV Injection 12

13 Systemic safety profile: Better than Bupivacaine 2,000,000 Patient-exposures without LAST Viscusi E, 2015 RAPM Neurotoxicity? 13

14 Neurologic Complications of PNBs and Toxicity of Local Anesthetics Admir Hadzic, MD, Professor of Anesthesiology Director, NAICE (North American Institute for Continuous Education) Director, NYSORA (The New York School of Regional Anesthesia) Consultant, Department of Anesthesiology, Ziekenhuis Oost-Limburg, Genk, Belgium Damjanovska M, Cvetko E, Hadzic A. Anaesthesia Dec;70(12): NO Neurotoxicity! 14

15 Nerve Blocks Not FDA Approved 15

16 PAIN at REST Hadzic et al.anesthesiology, June 2016 PAIN w ACTIVITY Hadzic et al.anesthesiology, June

17 ABILITY TO WALK? Hadzic et al.anesthesiology, June 2016 Plasma Levels Liposome Bupivacaine: after FNB Hadzic et al.anesthesiology, June

18 Exparel in ISB for Shoulder Sx 50 Patients Rotator Cuff or Shoulder Replacement Sx n= 24 pts Bupivacaine 0.25% 15ml n= 26 pts Exparel 10ml + 5ml bupi 0.25% All blocks preoperatively within 30 min of Surgery All patients received GA for surgery Onset times, VAS scores, Sleep, Opioids Vandepitte et al.nwac, April 2016 (Ethics Committee ZOL, Belgium, IND FAGG, Belgium FDA Equivalent Vandepitte et al.nwac, April 2016 (Ethics Committee ZOL, Belgium, IND FAGG, Belgium FDA Equivalent Vandepitte et al.nwac, April 2016 (Ethics Committee ZOL, Belgium, IND FAGG, Belgium FDA Equivalent 18

19 Nerve Blocks Not FDA Approved Current Research? Liposome Bupivacaine (Exparel) Current Uses and Future 19

20 Summary Possible Revolution in Acute Pain Rx Will catheters be replaced - NO Best consider as an additive to LA? More RCT needed Dose-ranging studies needed Best sites for injection? Mixture with other LAs studies needed Future - Exciting 20