Exparel, what do we need to know?

Sorry guys I haven’t posted for a little while. I was doing some reflection on myself. Anyway, I am back.

A friend of mine suggested a topic on Exparel and it is getting more widely used within the last couple of years. So I figure it is a good topic to discuss as it is relevant to our daily practice.          download (1)

Exparel is essentially liposomal bupicavaine. The liposome patented as Depoform.  It is a multivesicular spherical lipid particles in a honeycomb shape shown as above. It is hydrophilic side encapsulates the drug. It is approved for the surgical site infiltration and not approved for paracervical block. It is in phase 2/3 for most of the peripheral nerve blocks. The encapsulation of bupivacaine provides longer duration for post-op analgesia via degradation of the lipid membrane. The MOA is demonstrated as below.


It has shown that it provides several major benefits as below:

  • long lasting pain reduction 0-24 hours post surgery
  • Used to decrease opioid usage in surgical patients from 0- 72 hours postoperatively
  • Low systemic exposure and under cardiac threshold  with great safety profile

Dosing should be based on the surgical site instead of weight-based.  Bupivacaine liposomal injectable suspension follows a two-compartment model. Initially, first order short-term release followed by zero-order release over an extended period of time as free bupivacaine in the solution is immediately available to anesthetize the surgical site, and enclosed bupivacaine released gradually over an extended period of time.

  • May dilute in up to 280 ml of sterile saline to increase volume
  • Bupivacaine plain must be less than 50% of the bupivacaine liposomal dose
  • Inject above, below fascia and subcutaneous tissue
  • It has been shown to be used effectively in peripheral blocks such as interscale block, intercostal block, femoral nerve block, epidural block, ankle block etc.



Untitled What the study found is that liposome bupivacaine had clinically meaningful interactions with other local anesthetics, including lidocaine, ropivacaine, mepivacaine, or bupivacaine HCl (at liposome bupivacaine to bupivacaine HCl ratios < 2:1), which resulted in substantial displacement and release of free bupivacaine from liposomes . . . Liposome bupivacaine may be locally administered after • 20 minutes following local administration of lidocaine, ropivacaine, or mepivacaine. In addition, caution should exercised in patients with liver disease.

It is recommended by EXPAREl manufacture that the administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL.

In terms of efficacy of pain control compared to plain bupivacaine, there were mixed results on postop pain control comparing using other local anesthetics to Exparel. Some studies have demonstrated inferior pain control or no difference with Exparel. However, it has shown decreased hospital stay and early ambulation with Exparel group. As we know Exparel is $285 compared to bupivacaine plain for $2.80. However, considering the shorter hospital stay, it is overall cost effective.

Side effects include:

  • mild dizziness or drowsiness;
  • nausea, vomiting;
  • constipation;
  • itching;
  • headache, back pain; or.
  • swelling in your hands or feet.

Severity and frequency of the common side effects were similar with Exparel compared to other local anesthetics such as bupivacaine (62% vs. 75%). Local toxicity was less observed with Exparel than traditional plain bupivacaine.

Overall it appears that Exparel has its place in multi-modal pain management. Certain blocks may not benefits significantly from the use of Exparel.

Time to peak:

  • Bunionectomy: 2 h
  • Hemorrhoidectomy: 0.5 h
  • Inguinal hernia: 12 h
  • Total Knee Arthroplasty: 36 h

We should be aware that local toxicity may still occur but may occur a lot later than traditional local anesthetics.


  • Bagsby, D.T, Ireland, P.H., & Meneghini, M. ( 2014). Liposomal Bupivacaine Versus Traditional Periarticular Injection for Pain Control After Total Knee Athroplasty. Journal of Arthroplasty. (29) 1687-1690
  • Halawi, M.J, Grant, S.A., & Bolognesi, M.P. (2015). Multimodal analgesia for total joint arthroplasty. Orthopedics, 38, 616-625.
  • Schroer WC1, Diesfeld PG1, LeMarr AR1, Morton DJ1, Reedy ME1. (2015). Does Extended-Release Liposomal Bupivacaine Better Control Pain Than Bupivacaine After Total KneeArthroplasty (TKA)? A Prospective, Randomized Clinical Trial. J Arthroplasty. 30(9 Suppl):64-7. doi: 10.1016/j.arth.2015.01.059. Epub 2015 Jun 3.
  • Surdam, J.W.,  Licini D.J, Baynes N.T., & Arce B.R. (2015) The use of exparel(liposomal bupivacaine) to manage postoperative pain in unilateral total kneearthroplasty patients. J Arthroplasty. 30(2):325-9. doi: 10.1016/j.arth.2014.09.004.
  • Vendittoli, P., Makinen, P., Drolet, P., Lavigne, M., Fallaha, M., Guertin, M., & Varin, F. (2006). A multimodal analgesia protocol for total knee arthroplasty. Bone & Joint Surgery, 88, 282-289.
  • http://www.exparel.com/

Please let me know your thoughts on Exparel if you have used in your practice.



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