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Admir Hadzic, MD, Professor of AnesthesiologyDirector, 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

Liposome Bupivacaine (Exparel)Current Uses and Future

Goals:• Catheters• Future: Liposome bupivacaine • Mechanism of action• Current clinical uses• Systemic and NeuroToxicity Concerns• Local tissue and Neurotoxicity• Current research

DisclosureResearch grants: GSK, Baxter, Pacira

Advisor: GE, Sonosite, BD, B Braun, LifeTech

Consultant: Pacira Pharmaceuticals

Royalty income: BBraun Medical

Avenue-V, LLC

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In an ideal world

Catheters would be

BEST analgesic solution

Problems with

Catheters?

NOStandards?

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Complications?

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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%

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?

DepoFoamR Structure

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Current Clinical use

FDA Approved?Soft tissue infiltration

Local Infiltration into Surgical Site

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DATA?

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Dasta et al., Curr Med Res Opin, 2012; 28, 1609‐15.

Dasta et al., Curr Med Res Opin, 2012; 28, 1609‐15.

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Dasta et al., Curr Med Res Opin, 2012; 28, 1609‐15.

LIA – Total Knee ReplacementBarrington et al., Am J Orth, 2013.

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Infiltration for hemorrhoidectomy(Standard anal block)

Infiltration for abdominal surgery (TAP infiltration)

=

SURGICAL SITE Hemorrhoidectomy

SURGICAL SITE abdominal wall

CAN DILUTE TO REQUIRED VOLUME

Exparel 266mg (20ml) l

Exparel 266mg + 20ml NaCl = 40ml solution

0.25% BupivacaineNo mixing with other LA (liposome stability)

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LAST Scare

Time, Hours

0 24 48 72 96

500

400

300

200

100

0

Plasm

a Bupivacaine HCl C

oncentration (ng/m

L) CNS Toxicity:2,500 to 4,000 ng/ml

PLASMA LEVEL OF EXPAREL AFTER SOFT TISSUE INJECTION

Exparel 266mg

Bupivacaine 100mg

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Inadvertent IV

Injection?

IV INJECTION in dogs

3x

CNS Toxicity:2,500 to 4,000 ng/ml

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

Inadvertent IV Injection?

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Systemic safety profile: Better than Bupivacaine

2,000,000Patient-exposures

without LAST Viscusi E, 2015 RAPM

Neurotoxicity?

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Neurologic Complications of PNBs and Toxicity of Local Anesthetics

Admir Hadzic, MD, Professor of AnesthesiologyDirector, 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

NO Neurotoxicity!

Damjanovska M, Cvetko E, Hadzic A. Anaesthesia. 2015 Dec;70(12):1418-26

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Nerve BlocksNot FDA

Approved

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Hadzic et al .Anesthesiology, June 2016

PAIN at REST

Hadzic et al .Anesthesiology, June 2016

PAIN w ACTIVITY

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Hadzic et al .Anesthesiology, June 2016

ABILITY TO WALK?

Plasma Levels Liposome Bupivacaine:after FNB

Hadzic et al .Anesthesiology, June 2016

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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 SurgeryAll patients received GA for surgeryOnset 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

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Nerve BlocksNot FDA

Approved

Current Research?

Liposome Bupivacaine (Exparel)Current Uses and Future

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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