Sandhu HK, et al. Effectiveness of Standard Local Anesthetic Bupivacaine and Liposomal Bupivacaine for Postoperative Pain Control in Patients Undergoing Truncal Incisions: A Randomized Clinical Trial. JAMA Netw Open. 2021 Mar 1;4(3):e210753. doi: 10.1001/

Yesterday, we discussed the legalities of off-label prescribing in pediatric anesthesia and how that climate is changing with regard to drug company advertising. Today, we’ll extend that discussion to a topic that’s recently been in our literature – the use of the supposedly “long-acting” local anesthetic called liposomal bupivacaine (Exparel).

Exparel was initially approved for surgical infiltration in 2011, but not as a “long-acting” preparation. More recently, it has been approved for use in brachial plexus block only. Notably, this was the first time the FDA granted an indication for a local anesthetic for a specific type of regional nerve block. They did so, probably in response to mounting criticism that the FDA was not doing enough to stem perioperative opioid use. But since its original approval, post-marketing studies on the effectiveness of Exparel have been mixed, at best.

Sandhu et al, performed a randomized and blinded (to the patient and study team but not the surgeon) study comparing plain bupivacaine and liposomal bupivacaine for “truncal” incisions, which included sternotomy, thoracotomy, minithoracotomy, and laparotomy in adults. A total of 140 patients per group were evaluated. The local anesthetic was injected into the tissue surrounding the incision at the time of closure. In brief, there were no differences in indices of postoperative pain control (e.g., pain scores, opioid use) or patient satisfaction up to and including postoperative day #3.

The February 2021 issue of Anesthesiology also contains some important updates on this effectiveness. In a systematic review and meta-analysis, Hussain et al. pooled the results from 9 trials that included 619 patients and concluded that “High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks.” In the same issue, Ilfeld et al. published a comprehensive review of all studies that have examined the effectiveness of Exparel and concluded: “The preponderance of evidence fails to support the routine use of liposomal bupivacaine over standard local anesthetics.” These articles were accompanied by an editorial written by Dr. Mary Ellen McCann of Boston Children’s. Dr. McCann and I were on the same FDA advisory committee that evaluated the use of Exparel for regional nerve blocks. Even the studies the company submitted for approval showed marginal effectiveness, not only over plain bupivacaine, but even when compared with saline placebo. In her editorial, Dr. McCann writes:

“Once Exparel was approved, Pacira Biosciences began an aggressive and powerful marketing strategy. Between 2013 and 2019, they paid $25.8 million to more than 27,000 physicians for a variety of services including compensation for being a speaker or faculty at nonaccredited educational events. Sales of liposomal bupivacaine increased during this time with the company reporting a 25% growth in 2019 over 2018 with full-year revenues of $421 million in 2019. The cost of a single dose of 266 mg of Exparel brand liposomal bupivacaine is about $334. Nonliposomal bupivacaine costs about $3 per dose.”

My personal bias against using liposomal bupivacaine for regional nerve blocks is that there is no evidence (to my knowledge) that its accidental intravascular injection can be readily rescued by administration of intralipid. Administration of local anesthetic into a nerve sheath is much more likely to result in an accidental intravascular injection than indirect surgical infiltration into an open wound.

What’s the bottom line for us, as pediatric anesthesia practitioners? It seems to me that if liposomal bupivacaine was impressively better than plain bupivacaine, and worth its extra cost, we would know it by now, and its use would already by widespread in children. Until that happens, there is no reason to use it, and plenty of reasons to avoid it.