This article reviews the human and veterinary literature regarding liposome encapsulated bupivacaine use in dentistry and oral and maxillofacial surgery. The purpose of this review is to present available information on this local anesthetic in a manner that will allow veterinary dentists and oral and maxillofacial surgeons to use evidence-based information when considering incorporating liposomal bupivacaine into their practice. The twelve human clinical studies and three veterinary reports that met the literature search criteria do not support the use of liposomal bupivacaine in veterinary dentistry and oral and maxillofacial surgery.
SnyderCJSnyderLBC. Effect of mepivacaine in an infraorbital nerve block on minimum alveolar concentration of isoflurane in clinically normal anesthetized dogs undergoing a modified form of dental dolorimetry. J Am Vet Med Assoc. 2013;242(2):199-204.
BeckmanBW. Pathophysiology and management of surgical and chronic oral pain in dogs and cats. J Vet Dent. 2006;23(1):50-60.
4.
LamontLA. Multimodal pain management in veterinary medicine: the physiologic basis of pharmacologic therapies. Vet Clin North Am Small Anim Pract. 2008;38(6):1173-1186, v.
5.
EvansSWMcCahonRA. Management of postoperative pain in maxillofacial surgery. Br J Oral Maxillofac Surg. 2019;57(1):4-11.
6.
KellyDJAhmadMBrullSJ. Preemptive analgesia II: recent advances and current trends. Can J Anaesth. 2001;48(11):1091-1101.
7.
TriegerNGillenGH. Bupivacaine anesthesia and post-operative analgesia in oral surgery. Anesth Prog. 1979;26(1):20-23.
8.
Lago-MéndezLDiniz-FreitasMSenra-RiveraCGude-SampedroFGándara ReyJMGarcía-GarcíaA. Relationships between surgical difficulty and postoperative pain in lower third molar extractions. J Oral Maxillofac Surg. 2007;65(5):979-983.
9.
WoolfCJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2-S15.
10.
GlennBDrumMReaderAFowlerSNussteinJBeckM. Does liposomal bupivacaine (exparel) significantly reduce postoperative pain/numbness in symptomatic teeth with a diagnosis of necrosis? A prospective, randomized, double-blind trial. J Endod. 2016;42(9):1301-1306.
11.
BeckmanB. Anesthesia and pain management for small animals. Vet Clin North Am Small Anim Pract.2013;43(3):669-688.
12.
ReiterAMGracisM, eds. BSAVA Manual of Canine and Feline Dentistry and Oral Surgery. 4th ed. British Small Animal Veterinary Association; 2016.
13.
SnyderLCSnyderCBeebeD. Anesthesia and pain management. In: LobpriseHBDoddJR, eds. Wiggs’s Veterinary Dentistry: Principles and Practice. 2nd ed. John Wiley & Sons; 2019:177–181.
14.
DeclouxDOuanounouA. Local anaesthesia in dentistry: a review. Int Dent J. 2021;71(2):87-95.
15.
GrubbTLobpriseH. Local and regional anaesthesia in dogs and cats: overview of concepts and drugs (part 1). Vet Med Sci. 2020;6(2):209-217.
16.
TaylorAMcLeodG. Basic pharmacology of local anaesthetics. BJA Educ. 2020;20(2):34-41.
17.
PascoePJ. Anesthesia and pain management. In: VerstraeteFJMLommerMJArziB, eds Oral and Maxillofacial Surgery in Dogs and Cats. 2nd ed. Elsevier Health Sciences; 2019:22–28.
18.
SnyderLBCSnyderCJHetzelS. Effects of buprenorphine added to bupivacaine infraorbital nerve blocks on isoflurane minimum alveolar concentration using a model for acute dental/oral surgical pain in dogs. J Vet Dent. 2016;33(2):90-96.
19.
AguiarJChebrouxAMartinez-TaboadaFLeeceEA. Analgesic effects of maxillary and inferior alveolar nerve blocks in cats undergoing dental extractions. J Feline Med Surg. 2015;17(2):110-116.
20.
ChapmanPJGanendranA. Prolonged analgesia following preoperative bupivacaine neural blockade for oral surgery performed under general anesthesia. J Oral Maxillofac Surg. 1987;45(3):233-235.
21.
HolmanSDGierbolini-NoratEMLukasikSLCampbell-MaloneRDingPGermanRZ. Duration of action of bupivacaine hydrochloride used for palatal sensory nerve block in infant pigs. J Vet Dent. 2014;31(2):92-95.
LeroPTMulherinDRJensenOBerryTDanesiHRazookSJ. A prospective, randomized, open-label study comparing an opioid-sparing post surgical pain management protocol with and without liposomal bupivacaine for full-arch implant surgery. Int J Oral Maxillofac Implants. 2018;33(5):1155-1164
25.
TschoppCTramèrMRSchneiderAZaarourMEliaN. Benefit and harm of adding epinephrine to a local anesthetic for neuraxial and locoregional anesthesia: a meta-analysis of randomized controlled trials with trial sequential analyses. Anesth Analg. 2018;127(1):228-239.
26.
PatacsilJAMcAuliffeMSFeyhLSSigmonLL. Local anesthetic adjuvants providing the longest duration of analgesia for single-injection peripheral nerve blocks in orthopedic surgery: a literature review. AANA J. 2016;84(2):95-103.
27.
RenckHHassanHG. Epinephrine as an adjuvant to amino-amide local anesthetics does not prolong their duration of action in infraorbital nerve block in the rat. Acta Anaesthesiol Scand. 1992;36(5):387-392.
28.
DesaiNAlbrechtEEl-BoghdadlyK. Perineural adjuncts for peripheral nerve block. BJA Educ. 2019;19(9):276-282.
29.
ModiMRastogiSKumarA. Buprenorphine with bupivacaine for intraoral nerve blocks to provide postoperative analgesia in outpatients after minor oral surgery. J Oral Maxillofac Surg. 2009;67(12):2571-2576.
GoodchildJHDonaldsonM. Does liposomal bupivacaine fulfill an unmet need in dentistry?Gen Dent. 2018;66(5):14-16.
32.
DrumMReaderANussteinJFowlerS. Successful pulpal anesthesia for symptomatic irreversible pulpitis. J Am Dent Assoc. 2017;148(4):267-271.
33.
ApseloffGOnelEPatouG. Time to onset of analgesia following local infiltration of liposome bupivacaine in healthy volunteers: a randomized, single-blind, sequential cohort, crossover study. Int J Clin Pharmacol Ther. 2013;51(5):367-373.
DamjanovskaMCvetkoEHadzicA, et al.Neurotoxicity of perineural vs intraneural-extrafascicular injection of liposomal bupivacaine in the porcine model of sciatic nerve block. Anaesthesia. 2015;70(12):1418-1426.
37.
RichardBMNewtonPOttLR, et al.The safety of EXPAREL ® (bupivacaine liposome injectable suspension) administered by peripheral nerve block in rabbits and dogs. J Drug Deliv. 2012;2012:962101. doi: 10.1155/2012/962101.
38.
McAlvinJBPaderaRFShankarappaSA, et al.Multivesicular liposomal bupivacaine at the sciatic nerve. Biomaterials. 2014;35(15):4557-4564.
LeKMCastonSSHossetterJMHay KrausBL. Comparison of analgesic and tissue effects of subcutaneous perineural injection of liposomal bupivacaine and bupivacaine hydrochloride in horses with forelimb lameness induced via circumferential clamp. Am J Vet Res. 2020;81(7):551-556.
41.
Gordon-EvansWJSuhHYGuedesAG. Controlled, non-inferiority trial of bupivacaine liposome injectable suspension. J Feline Med Surg. 2020;22(10):916-921.
42.
RichardBMOttLRHaanD, et al.The safety and tolerability evaluation of DepoFoam bupivacaine (bupivacaine extended-release liposome injection) administered by incision wound infiltration in rabbits and dogs. Expert Opin Investig Drugs. 2011;20(10):1327-1341.
43.
RichardBMRickertDENewtonPE, et al.Safety evaluation of EXPAREL (DepoFoam bupivacaine) administered by repeated subcutaneous injection in rabbits and dogs: species comparison. J Drug Deliv. 2011;2011:467429.
44.
LascellesBDXRausch-DerraLCWoffordJAHuebnerM. Pilot, randomized, placebo-controlled clinical field study to evaluate the effectiveness of bupivacaine liposome injectable suspension for the provision of post-surgical analgesia in dogs undergoing stifle surgery. BMC Vet Res. 2016;12(1)168: doi:10.1186/s12917-016-0798-1.
45.
ReaderRCMcCarthyRJSchultzKL, et al.Comparison of liposomal bupivacaine and 0.5% bupivacaine hydrochloride for control of postoperative pain in dogs undergoing tibial plateau leveling osteotomy. J Am Vet Med Assoc. 2020;256(9):1011-1019.
46.
ViscusiERSinatraROnelERamamoorthySL. The safety of liposome bupivacaine, a novel local analgesic formulation. Clin J Pain. 2014;30(2):102-110.
47.
IlfeldBMViscusiERHadzicA, et al.Safety and side effect profile of liposome bupivacaine (exparel) in peripheral nerve blocks. Reg Anesth Pain Med. 2015;40(5):572-582.
48.
BaxterRBramlettKOnelEDanielsS. Impact of local administration of liposome bupivacaine for postsurgical analgesia on wound healing: a review of data from ten prospective, controlled clinical studies. Clin Ther. 2013;35(3):312-320.e5.
49.
LieblichSEDanesiH. Liposomal bupivacaine use in third molar impaction surgery: INNOVATE study. Anesth Prog. 2017;64(3):127-135.
50.
OlsonMDMooreEJPriceDL. A randomized single-blinded trial of posttonsillectomy liposomal bupivacaine among adult patients. Otolaryngol Head Neck Surg. 2018;159(5):835-842.
51.
ChuaMEZuckermanJMStrehlowR6th, et al.Liposomal bupivacaine local infiltration for buccal mucosal graft harvest site pain control: a single-blinded randomized controlled trial. Urology. 2020;145:269-274.
52.
DayKMNairNMSargentLA.Extended release liposomal bupivacaine injection (exparel) for early postoperative pain control following palatoplasty. J Craniofac Surg. 2018;29(5):e525-e528.
53.
DayKMNairNMGrinerDSargentLA. Extended release liposomal bupivacaine injection (exparel) for early postoperative pain control following pharyngoplasty. J Craniofac Surg. 2018;29(3):726-730.
54.
BultemaKFowlerSDrumMReaderANussteinJBeckM. Pain reduction in untreated symptomatic irreversible pulpitis using liposomal bupivacaine (exparel): a prospective, randomized, double-blind trial. J Endod. 2016;42(12):1707-1712.
55.
HenryAWhiteheadSMehraP. Decreasing opioid usage during hospitalization in patients undergoing orthognathic surgery. J Oral Maxillofac Surg. 2020;78(10):e6-e7.
56.
FahmyMDChoRABrooksSRCampbellJGotcherJE. Reduction of postoperative narcotic usage following mandibular orthognathic surgeries: is exparel an effective agent?J Oral Maxillofac Surg. 2019;77(9):e65-e66.
57.
MagrawCPhamMNealT, et al.A multimodal analgesic protocol may reduce opioid use after third molar surgery: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;126(3):214-217.
58.
LieblichSEMisiekDOlczakJFleckHWatermanF. A retrospective cross-sectional study of the effect of liposomal bupivacaine on postoperative opioid prescribing after third molar extraction. J Oral Maxillofac Surg. Published online 2021. 2021 Jul;79(7):1401-1408.e1. doi: 10.1016/j.joms.2021.02.012.
KlingKE. A Focus on Feline Dentistry. Proceedings from the Veterinary Dental Forum, November 15-18, 2018. Phoenix, AZ.
61.
GrubbTLobpriseH. Local and regional anaesthesia in dogs and cats: descriptions of specific local and regional techniques (part 2). Vet Med Sci. 2020;6(2):218-234.
62.
Castejón-GonzálezACReiterAM. Locoregional anesthesia of the head. Vet Clin North Am Small Anim Pract. 2019;49(6):1041-1061.
63.
DineA. Where is the evidence? A critical review of bias in the reporting of clinical data for exparel: A liposomal bupivacaine formulation. J Clin Res Bioeth. 2014;05(04):1–5. doi: https://doi.org/10.4172/2155-9627.1000189
64.
HamiltonTWAthanassoglouVTrivellaM, et al.Liposomal bupivacaine peripheral nerve block for the management of postoperative pain. Cochrane Database Syst Rev. 2016;(8):CD011476. doi: 10.1002/14651858.CD011476.pub2.
65.
KendallMCCastro AlvesLJDe OliveiraG. Liposome bupivacaine compared to plain local anesthetics to reduce postsurgical pain: an updated meta-analysis of randomized controlled trials. Pain Res Treat. 2018;2018:1-10.
66.
HussainNBrullRSheehyB, et al.Perineural liposomal bupivacaine is not superior to nonliposomal bupivacaine for peripheral nerve block analgesia: a systematic review and meta-analysis. Anesthesiology. 2021;134(2):147-164.
