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Title Liposomal Bupivacaine May Prove to Provide Adequate Long-Term Local Anesthesia
Clinical Question Is liposomal bupivacaine (Exparel) effective in providing extended local anesthesia and reducing post-operative opioid use in a variety of dental procedures?
Clinical Bottom Line For patients receiving endodontic care or third molar extractions, there is not enough evidence to support the conclusion that liposomal bupivacaine is any more effective than other anesthesia medications. This is supported by a randomized double-blinded study in which buccal infiltration of liposomal bupivacaine was shown to not achieve clinically relevant levels of anesthesia for prolonged periods of time. A systematic review of liposomal bupivacaine showed inconclusive evidence to support that liposomal bupivacaine resulted in a greater depth of anesthesia as compared to bupivacaine hydrochloride, or resulted in a significant reduction in post-operative opioid consumption.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 27461787Glenn/2016100 patients with pulpal necrosis Randomized Controlled Trial
Key resultsIn patients with symptomatic pulpal necrosis experiencing moderate to severe preoperative pain, pain was not adequately reduced to a point to achieve clinical success with a 4.0-ml buccal infiltration of liposomal bupivacaine. Although liposomal bupivacaine did result in significantly longer soft tissue numbness on days 1 and 2, it did not result in a clinically significant success rate. Liposomal group success rate was 29% vs 22% for bupivacaine HCL group (p=.4684). Success was defined as no or mild postoperative pain and no narcotic use.
#2) 28146271Hamilton/201710 reports, 1377 participantsSystematic review of randomized trials
Key resultsTwo of the studies reported a lower cumulative pain score when compared to a salt-water placebo from 0 to 72 hours post-surgery (Golf 2011; Gorfine 2011). One study reported lower opioid consumption from 0 to 72 hours after surgery (Gorfine 2011), and three studies reported the number of participants not requiring postoperative opioids. These studies were not compared due to substantial heterogeneity (I2 =92%). When studies were performed evaluating liposomal bupivacaine to bupivacaine hydrochloride, no difference was found in reduction of pain from 0 to 72 hours (Smoot 2012). Due to the low quality and volume of evidence, the researchers’ confidence in the effect was limited, with most reports receiving a low to very low quality.
#3) n/aLieblich/201689 patients undergoing third molar extractionRandomized Controlled Trial
Key resultsSubjects were evaluated for post-operative pain levels after third molar extraction. The primary endpoint of 48-hr reduction in pain scores was statistically significant, with liposomal bupivacaine being significantly lower (P=.0226) than placebo. Significantly lower pain scores were also recorded at 24 hrs (P=.0192), 72 hrs (P=.0469), and at 96 hrs (P=.045). Lieblich et al. Analgesic Efficacy and Safety of Exparel (bupivacaine liposome injectable suspension) in Subjects Undergoing Third Molar Surgery: Preliminary Results of a Randomized Controlled Study. J Oral Maxillofac Surg 2016;74(9):e42-e43.
Evidence Search ("liposomes"[Pharmacological Action] OR "liposomes"[MeSH Terms] OR "liposomes"[All Fields] OR "liposomal"[All Fields]) AND ("bupivacaine"[MeSH Terms] OR "bupivacaine"[All Fields]) AND infiltration[All Fields] AND ("pain, postoperative"[MeSH Terms] OR ("pain"[All Fields] AND "postoperative"[All Fields]) OR "postoperative pain"[All Fields] OR ("postoperative"[All Fields] AND "pain"[All Fields]))
Comments on
The Evidence
Validity: Research by Lielblich H was a double-blinded randomized control trial that provided adequate follow up and compliance of the subjects. This article suffered from having a poor completion rate (50.2%) that was reportedly due to protocol deviations. The research by Glenn et al., was a double-blinded randomized control trial. Adequate follow-up and compliance were measured with a 5-day diary that was recorded nightly. The study had an adequate completion rate (88%), and recall bias was unlikely. The systematic review used here had two authors review and independently consider the trials for inclusion, assessed risk of bias, and extracted data. They followed the Cochrane Handbook for Systematic reviews of Interventions and evaluated the quality of evidence using GRADE. Perspective: The researchers did find promising results in the medical field to show liposomal bupivacaine’s ability to provide adequate local anesthesia for arthroplasties. This could be of particular benefit during TMJ arthroplasty. In a few of the studies evaluated during the systematic review performed by Hamilton et al., evidence pointed to the ability of liposomal bupivacaine to lower patients' post-operative opioid use and decrease patients' length of stay. These studies were evaluated to have a very low to low quality of evidence. The current published information warrants further research, particular in the field of dentistry, into the efficacy and pharmacodynamics of liposomal bupivacaine.
Applicability The use of liposomal bupivacaine for patients with symptomatic pulpal necrosis can occur in any general dentistry setting. Oral and maxillofacial surgeons primarily perform the surgical extraction of third molars, but any practitioner needing to alter oral cavity soft tissue can utilize the soft tissue anesthesia. One current pitfall for liposomal bupivacaine is that the FDA does not currently approve it for nerve blocks, which limits its use to strictly infiltrations. The drive to seek prolonged local anesthesia to prevent patient pain and reduce post-operative analgesic use is in direct line with dentistry’s mission statement.
Specialty/Discipline (Endodontics) (General Dentistry) (Oral Surgery)
Keywords Local anesthesia, liposomal bupivacaine
ID# 3208
Date of submission: 04/05/2017spacer
E-mail rathburn@livemail.uthscsa.edu
Author Sean Rathburn
Co-author(s) e-mail
Faculty mentor/Co-author Jack Vizuete, DDS
Faculty mentor/Co-author e-mail VizueteJ@uthscsa.edu
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?)
post a rationale
None available
Comments and Evidence-Based Updates on the CAT
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by Thomas O'Connor (San Antonio, TX) on 09/30/2022
I conducted a PubMed search on this topic in September 2022 and found a more recent systematic review of randomized clinical trials by Ji 2021, PubMed: 33862580. This review greatly expands on the previous systematic review cited in the CAT. Based on the inclusion criteria, the authors included 63 studies with 6770 subjects across medical and dental procedures. Results showed that 74% of RCTs found no significant pain relief compared to placebo. The authors also found that 85% of studies found no significant reduction in opioid consumption in the RCTs included. Of the studies that showed an increase in pain relief, they had an Odds Ratio of 14.31 of having a financial conflict of interest.

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