The Efficacy of Liposomal Bupivacaine for Opioid and Pain Reduction: A Systematic Review of Randomized Clinical Trials.

Background The opioid crisis has prompted surgeons to search for alternative postoperative methods of analgesia. Liposomal bupivacaine is a long-acting local anesthetic formulation used for pain, potentially reducing opioid use. Evaluation of liposomal bupivacaine as a viable alternative for pain management is needed. The objective was to assess the efficacy of randomized clinical trials (RCTs) of liposomal bupivacaine in postoperative pain management and opioid consumption. Material and Methods The authors extracted RCTs comparing liposomal bupivacaine versus placebo or active comparators for postoperative pain or opioid reduction from PubMED/MEDLINE, Cochrane Library, and ClinicalTrials.gov. Exclusion criteria included nonhuman studies, non-RCTs, pooled studies, and inability to access full text. The following variables were abstracted: surgical specialty, number of subjects, pain and opioid outcomes, and authors' financial conflicts of interest. Results We identified 77 published RCTs, of which 63 studies with a total of 6770 subjects met inclusion criteria. Liposomal bupivacaine did not demonstrate significant pain relief compared to placebo or active agents in 74.58% of RCTs. Of the studies evaluating narcotic use, liposomal bupivacaine did not show a reduction in opioid consumption in 85.71% of RCTs. Liposomal bupivacaine, when compared to standard bupivacaine or another active agent, yielded no reduction in opioid use in 83.33% and 100.00% of studies, respectively. Clinical trials with a financial conflict of interest relating to the manufacturer of liposomal bupivacaine were significantly more likely to show pain relief (OR: 14.31 [95% CI, 2.8, 73.10], P = 0.0001) and decreased opioid consumption (OR: 12.35 [95% CI 1.40, 109.07], P = 0.0237). Of the 265 unpublished RCTs on ClinicalTrials.gov, 47.54% were withdrawn, terminated, suspended, or completed without study results available. Conclusions The efficacy of liposomal bupivacaine for providing superior postoperative pain control relative to placebo or another active agent is not supported by a majority of RCTs. Underreporting of trial results and bias due to underlying financial relationships amongst authors are two major concerns that should be considered when evaluating the available evidence.