Liposomal bupivacaine and novel local anesthetic formulations

Prabhakar, Amit; Ward, Ceressa T.; Watson, Matthew R.; Sanford, Jay P.; Fiza, Babar; Moll, Vanessa; Kaye, Rachel; Hall, O. Morgan; Cornett, Elyse M.; Urman, Richard D.; Kaye, Alan D.

doi:10.1016/j.bpa.2019.07.012

Cited by 37 publications

(32 citation statements)

References 12 publications

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“…[81][82][83][84][85] Structurally, the liposomal local anesthetic preparation examined in this review features encapsulation by a multivesicular liposomal lipid bilayer, allowing sustained local anesthetic release, theoretically prolonging its effect up to 72 h after a single application. [86][87][88] Pharmacokinetic studies seem to corroborate this slow release, showing sustained plasma bupivacaine levels up to 96 h 86,87 and even 120 h after interscalene brachial plexus block. 87 However, our review of clinical evidence of effectiveness of the perineural route in prolonging the duration of peripheral nerve block analgesia has demonstrated disparity with the anticipated benefits.…”

Section: Discussionmentioning

confidence: 98%

Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia

et al. 2021

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Background Liposomal bupivacaine is purported to extend analgesia of peripheral nerve blocks when administered perineurally. However, evidence of the clinical effectiveness of perineural liposomal bupivacaine is mixed. This meta-analysis seeks to evaluate the effectiveness of perineural liposomal bupivacaine in improving peripheral nerve block analgesia as compared with nonliposomal local anesthetics. Methods The authors identified randomized trials evaluating the effectiveness of peripheral nerve block analgesic that compared liposomal bupivacaine with nonliposomal local anesthetics. The primary outcome was the difference in area under the receiver operating characteristics curve (AUC) of the pooled 24- to 72-h rest pain severity scores. Secondary outcomes included postoperative analgesic consumption, time to first analgesic request, incidence of opioid-related side effects, patient satisfaction, length of hospital stay, liposomal bupivacaine side effects, and functional recovery. AUC pain scores were interpreted in light of a minimal clinically important difference of 2.0 cm · h. Results Nine trials (619 patients) were analyzed. When all trials were pooled, AUC pain scores ± SD at 24 to 72 h were 7.6 ± 4.9 cm · h and 6.6 ± 4.6 cm · h for nonliposomal and liposomal bupivacaine, respectively. As such, perineural liposomal bupivacaine provided a clinically unimportant benefit by improving the AUC (95% CI) of 24- to 72-h pain scores by 1.0 cm · h (0.5 to 1.6; P = 0.003) compared with nonliposomal bupivacaine. Excluding an industry-sponsored trial rendered the difference between the groups nonsignificant (0.7 cm · h [−0.1 to 1.5]; P = 0.100). Secondary outcome analysis did not uncover any additional benefits to liposomal bupivacaine in pain severity at individual timepoints up to 72 h, analgesic consumption, time to first analgesic request, opioid-related side effects, patient satisfaction, length of hospital stay, and functional recovery. No liposomal bupivacaine side effects were reported. Conclusions Perineural liposomal bupivacaine provided a statistically significant but clinically unimportant improvement in the AUC of postoperative pain scores compared with plain local anesthetic. Furthermore, this benefit was rendered nonsignificant after excluding an industry-sponsored trial, and liposomal bupivacaine was found to be not different from plain local anesthetics for postoperative pain and all other analgesic and functional outcomes. High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Section: Discussionmentioning

confidence: 98%

Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia

et al. 2021

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“…Continuous catheters are not without limitations, however, including increased complexity to perform and maintain, catheter-related complications, and additional monitoring and follow-up requirements [249]. As such, controlled-release local anesthetic formulations have also been developed [257][258][259]. Liposomal bupivacaine has not demonstrated clinically meaningful benefits to postoperative pain control or opioid reduction when compared to conventional local anesthetics in local wound infiltration, periarticular injection, or peripheral nerve blockade [249,[260][261][262][263][264][265][266][267][268][269][270][271][272][273][274][275].…”

Section: Regional and Local Anesthesiamentioning

confidence: 99%

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

et al. 2021

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Surgical procedures are key drivers of pain development and opioid utilization globally. Various organizations have generated guidance on postoperative pain management, enhanced recovery strategies, multimodal analgesic and anesthetic techniques, and postoperative opioid prescribing. Still, comprehensive integration of these recommendations into standard practice at the institutional level remains elusive, and persistent postoperative pain and opioid use pose significant societal burdens. The multitude of guidance publications, many different healthcare providers involved in executing them, evolution of surgical technique, and complexities of perioperative care transitions all represent challenges to process improvement. This review seeks to summarize and integrate key recommendations into a “roadmap” for institutional adoption of perioperative analgesic and opioid optimization strategies. We present a brief review of applicable statistics and definitions as impetus for prioritizing both analgesia and opioid exposure in surgical quality improvement. We then review recommended modalities at each phase of perioperative care. We showcase the value of interprofessional collaboration in implementing and sustaining perioperative performance measures related to pain management and analgesic exposure, including those from the patient perspective. Surgery centers across the globe should adopt an integrated, collaborative approach to the twin goals of optimal pain management and opioid stewardship across the care continuum.

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“…Novel preparations of local anesthetics have also been studied. These new preparations allow for the extended duration of action of local anesthetics (25). One example is the preparation of bupivacaine with a liposomal bilayer, which allows for sustained release of local anesthetic for at least 72 hours after the injection, and this has the potential for decreasing opioid consumption in the postoperative period (25).…”

Section: Contextmentioning

confidence: 99%

Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future

Kaye¹,

Edinoff

Yan

et al. 2022

Anesth Pain Med

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: The treatment of pain, both acute and chronic, has been a focus of medicine for generations. Physicians have tried to develop novel ways to effectively manage pain in surgical and post-surgical settings. One intervention demonstrating efficacy is nerve blocks. Single-injection peripheral nerve blocks (PNBs) are usually preferred over continuous PNBs, since they are not associated with longer lengths of stay. The challenge of single injection PNBs is their length of duration, which at present is a major limitation. Novel preparations of local anesthetics have also been studied, and these new preparations could allow for extended duration of action of anesthetics. An emerging preparation of bupivacaine, exparel, uses a multivesicular liposomal delivery system which releases medication in a steady, controlled manner. Another extended-release local anesthetic, HTX-011, consists of a combination of bupivacaine and low-dose meloxicam. Tetrodotoxin, a naturally occurring reversible site 1 sodium channel toxin derived from pufferfish and shellfish, has shown the potential to block conduction of isolated nerves. Neosaxitoxin is a more potent reversible site 1 sodium channel toxin also found in shellfish that can also block nerve conduction. These novel formulations show great promise in terms of the ability to prolong the duration of single injection PNBs. This field is still currently in development, and more researchers will need to be done to ensure the efficacy and safety of these novel formulations. These formulations could be the future of pain management if ongoing research continues to prove positive effects and low side effect profiles.

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Liposomal bupivacaine and novel local anesthetic formulations

Cited by 37 publications

References 12 publications

Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia

Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future

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