Liposomal Bupivacaine in the Perioperative Setting

Local anesthetic drugs are crucial to an anesthesia provider’s practice. Local anesthesia creates temporary and reversible pain elimination in specific areas of the body.1 During the perioperative period, local anesthesia’s role in pain control leads to improved cardiac, respiratory and gastrointestinal functions; fewer blood clot-related complications; improved arterial graft survival; fewer complications from infection; reduced chronic postoperative pain; reduced mortality in high-risk patients; and reduced health care costs.2 It is used in a variety of situations, ranging from simple procedures such as removing damaged skin to complicated operations such as organ transplants1 or brain surgery.3 The duration of action of a local anesthetic depends on the route of administration, such as bolus injection or infusion.2 The development of new, long-acting local anesthetics like liposomal bupivacaine may allow anesthesia providers to better manage patients’ perioperative pain. In order to add a new anesthetic drug to their repertoires and broaden their practices, anesthesiology professionals should be familiar with the mechanisms of liposomal bupivacaine and its perioperative uses. 

Liposomal bupivacaine uses liposome technology to create an extended-release version of the local anesthetic bupivacaine.4 Bupivacaine, which was discovered in 1957, is a potent local anesthetic from the amide group of local anesthetics.5 It is offered in concentrations of 0.25, 0.5 and 0.75 percent and can be administered spinally, epidurally, by local infiltration or as a peripheral or caudal nerve block.5 While bupivacaine has a long duration of action relative to other local anesthetics,6 its anesthetic effects can be extended even further through liposome technology.2 Liposomes are microscopic structures consisting of a phospholipid bilayer around an aqueous core.2 They are biodegradable, natural, non-toxic, non-immunogenic and highly bioavailable lipid molecules.7 Multivesicular liposomes, which make up liposomal bupivacaine,4 consist of nonconcentric (i.e., not having a common center) lipid bilayers that lead to increased stability and longer duration of drug release.2 Over time, scientists have developed the technology of liposomal bupivacaine to minimize side effects and increase efficacy.7 The encapsulation of bupivacaine inside liposomes allows for a long-lasting, safe alternative to traditional local anesthetics. 

Liposomal bupivacaine shows a variety of benefits in clinical and perioperative settings. According to a review by Chahar and Cummings, liposomal bupivacaine via local infiltration extends analgesia beyond the intraoperative period, providing effective postsurgical pain relief.2 Rogobete et al. also state that clinical use of liposomal bupivacaine leads to impressive pain control, quick patient recovery and reduced treatment costs.7 Additionally, liposome technology minimizes side effects, particularly cardiotoxicity, neurotoxicity and tissue lesions.7 Some studies show that liposomal bupivacaine may significantly reduce opioid use after a procedure.4,8,9 However, evidence is lacking on the efficacy of liposomal bupivacaine compared to standard local anesthetics. Separate reviews and meta-analyses by Uskova and O’Connor,10 Yayac et al.11 and Gabriel and Ilfeld12 have shown a scarcity of high-quality data on liposomal bupivacaine compared to other local anesthetics. Meanwhile, large-scale analyses by Kendall et al.13 and Pichler et al.14 found no clinically relevant improvement in patients who used liposomal bupivacaine instead of standard analgesics. Hyland et al.’s prospective randomized controlled trial found no significant clinical benefit of liposomal bupivacaine over standard care in total knee arthroplasty.15 Though liposomal bupivacaine has many advantages, more research is needed to compare it to other types of local anesthesia. 

Local anesthesia is vital to pain control during the perioperative period. These anesthetic drugs can be administered in many ways and different molecular compositions, including those using liposome technology. Liposomal bupivacaine is an extended-release formula that may produce long-lasting postoperative analgesia, lessen the need for opioids and reduce risk of complications. Future researchers should aim to produce high-quality, adequately powered, prospective, randomized, controlled trials to compare liposomal bupivacaine to unencapsulated local anesthetics.12 

1.Vardanyan RS, Hruby VJ. Local Anesthetics. In: Vardanyan RS, Hruby VJ, eds. Synthesis of Essential Drugs. Amsterdam: Elsevier; 2006:9–18. 

2.Chahar P, Cummings KC, III. Liposomal bupivacaine: A review of a new bupivacaine formulation. Journal of Pain Research. 2012;5:257–264. 

3.Potters J-W, Klimek M. Local anesthetics for brain tumor resection: Current perspectives. Local and Regional Anesthesia. 2018;11:1–8. 

4.Malik O, Kaye AD, Kaye A, Belani K, Urman RD. Emerging roles of liposomal bupivacaine in anesthesia practice. Journal of Anaesthesiology, Clinical Pharmacology. 2017;33(2):151–156. 

5.Shafiei FT, Lopez J. Bupivacaine. StatPearls. Web: StatPearls Publishing LLC; August 17, 2019. 

6.Ilfeld BM. Liposomal Bupivacaine: Its Role in Regional Anesthesia and Postoperative Analgesia. Advances in Anesthesia. 2014;32(1):133–147. 

7.Rogobete AF, Bedreag OH, Sărăndan M, et al. Liposomal bupivacaine – New trends in Anesthesia and Intensive Care Units. Egyptian Journal of Anaesthesia. 2015;31(1):89–95. 

8.Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine Extended-Release Liposome Injection for Prolonged Postsurgical Analgesia in Patients Undergoing Hemorrhoidectomy: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial. Diseases of the Colon & Rectum. 2011;54(12):1552–1559. 

9.Patel MA, Gadsden JC, Nedeljkovic SS, et al. Brachial Plexus Block with Liposomal Bupivacaine for Shoulder Surgery Improves Analgesia and Reduces Opioid Consumption: Results from a Multicenter, Randomized, Double-Blind, Controlled Trial. Pain Medicine. 2019;21(2):387–400. 

10.Uskova A, O’Connor JE. Liposomal bupivacaine for regional anesthesia. Current Opinion in Anesthesiology. 2015;28(5):593–597. 

11.Yayac M, Li WT, Ong AC, Courtney PM, Saxena A. The Efficacy of Liposomal Bupivacaine Over Traditional Local Anesthetics in Periarticular Infiltration and Regional Anesthesia During Total Knee Arthroplasty: A Systematic Review and Meta-Analysis. The Journal of Arthroplasty. 2019;34(9):2166–2183. 

12.Gabriel RA, Ilfeld BM. An Updated Review on Liposome Bupivacaine. Current Anesthesiology Reports. 2019;9(3):321–325. 

13.Kendall MC, Castro Alves LJ, De Oliveira G, Jr. Liposome Bupivacaine Compared to Plain Local Anesthetics to Reduce Postsurgical Pain: An Updated Meta-Analysis of Randomized Controlled Trials. Pain Research and Treatment. 2018;2018:5710169. 

14.Pichler L, Poeran J, Zubizarreta N, et al. Liposomal Bupivacaine Does Not Reduce Inpatient Opioid Prescription or Related Complications after Knee Arthroplasty: A Database Analysis. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2018;129(4):689–699. 

15.Hyland SJ, Deliberato DG, Fada RA, Romanelli MJ, Collins CL, Wasielewski RC. Liposomal Bupivacaine Versus Standard Periarticular Injection in Total Knee Arthroplasty With Regional Anesthesia: A Prospective Randomized Controlled Trial. The Journal of Arthroplasty. 2019;34(3):488–494. 

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