Liposomal Bupivacaine Reduces Opioid Use Following Third Molar Surgery: A Randomized Controlled Trial

Third molar extraction is one of the most common procedures associated with initial opioid exposure in adolescents. Exparel (liposomal bupivacaine) offers a potential strategy to reduce opioid use.

The study purpose was to measure and compare postoperative pain and opioid use in patients receiving liposomal bupivacaine plus standard local anesthesia versus standard local anesthesia alone following third molar extractions.

This randomized, single-blind study enrolled American Society of Anesthesiologists I-II subjects undergoing extractions of 4 impacted third molars under intravenous sedation in the outpatient setting. All procedures were performed by a single surgeon at a private practice in California between January, 2023 and June, 2025. Exclusion criteria included pregnancy/lactation, allergy to local anesthetics or analgesics, and medical contraindications to sedation or surgery.

The predictor variable was anesthetic agent, and subjects were randomly assigned to receive either standard local anesthesia (lidocaine and bupivacaine) alone or standard local anesthesia plus liposomal bupivacaine.

The outcome variable was therapeutic effect measured using opioid use (intake of at least 1 pill), cumulative opioid consumption (morphine milligram equivalent), and pain scores (FACES pain scale) through postoperative day 5.

The covariates were age and sex.

Opioid use was compared using a χ² test, cumulative opioid consumption using the Mann-Whitney U test, and postoperative pain scores using a linear mixed-effects model. Analyses were restricted to postoperative days 0 to 5, with statistical significance set at P< .05.

A total of 93 subjects were enrolled with a mean age of 17 (SD 2.7) and 47 (51%) were female. There were 47 (51%) and 46 (49%) in the control and liposomal bupivacaine groups, respectively. Opioid use differed significantly between groups: 25/47 (53%) in the control group versus 12/46 (26%) in the liposomal bupivacaine group (P= .022). Cumulative mean morphine milligram equivalent also differed significantly: 12.4 in the control group compared to 5.7 in the liposomal bupivacaine group (P= .015). Postoperative pain decreased significantly over time in both groups, with no significant differences in pain scores between the liposomal bupivacaine (treatment) and standard local anesthesia (control) groups (P= .3).

Liposomal bupivacaine use during third molar extractions significantly reduced opioid consumption without increasing reported pain compared to controls.