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Randomized Controlled Trial
. 2022 Jun 1;157(6):481-489.
doi: 10.1001/jamasurg.2022.0713.

Efficacy of Liposomal Bupivacaine and Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Periarticular Anesthetic for Patients Undergoing Knee Replacement: A Randomized Clinical Trial

Thomas W Hamilton  1 , Ruth Knight  2 , Jamie R Stokes  2 , Ines Rombach  3 , Cushla Cooper  4 , Loretta Davies  4 , Susan J Dutton  2 , Karen L Barker  5   6 , Jonathan Cook  2 , Sarah E Lamb  2 , David W Murray  1 , Lisa Poulton  4 , Ariel Wang  2 , Louise H Strickland  1 , Bernard H Van Duren  7 , Jose Leal  3 , David Beard  2 , Hemant G Pandit  7 ; Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK) Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Efficacy of Liposomal Bupivacaine and Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Periarticular Anesthetic for Patients Undergoing Knee Replacement: A Randomized Clinical Trial

Thomas W Hamilton et al. JAMA Surg. .

Abstract

Importance: More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain.

Objective: To evaluate the efficacy and cost-effectiveness of periarticular liposomal bupivacaine for recovery and pain management after knee replacement.

Design, setting, and participants: This multicenter, patient-blinded, pragmatic, randomized clinical superiority trial involved 533 participants at 11 institutions within the National Health Service in England. Adults undergoing primary unilateral knee replacement for symptomatic end-stage osteoarthritis were enrolled between March 29, 2018, and February 29, 2020, and followed up for 1 year after surgery. Follow-up was completed March 1, 2021. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis.

Interventions: Two hundred sixty-six milligrams of liposomal bupivacaine admixed with 100 mg of bupivacaine hydrochloride compared with 100 mg of bupivacaine hydrochloride alone (control) administered by periarticular injection at the time of surgery.

Main outcome and measures: The coprimary outcomes were Quality of Recovery 40 (QoR-40) score at 72 hours and pain visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2, and 3; cumulative opioid consumption for 72 hours; functional outcomes and quality of life at 6 weeks, 6 months, and 1 year; and cost-effectiveness for 1 year. Adverse events and serious adverse events up to 12 months after randomization were also assessed.

Results: Among the 533 participants included in the analysis, the mean (SD) age was 69.0 (9.7) years; 287 patients were women (53.8%) and 246 were men (46.2%). Baseline characteristics were balanced between study groups. There was no difference between the liposomal bupivacaine and control groups in QoR-40 score at 72 hours (adjusted mean difference, 0.54 [97.5% CI, -2.05 to 3.13]; P = .64) or the pain VAS score AUC at 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P = .06). Analyses of pain VAS and QoR-40 scores demonstrated only 1 statistically significant difference, with the liposomal bupivacaine arm having lower pain scores the evening of surgery (adjusted difference -0.54 [97.5% CI, -1.07 to -0.02]; P = .02). No difference in cumulative opioid consumption and functional outcomes was detected. Liposomal bupivacaine was not cost-effective compared with the control treatment. No difference in adverse or serious adverse events was found between the liposomal bupivacaine and control groups.

Conclusions and relevance: This study found no difference in postoperative recovery or pain associated with the use of periarticular liposomal bupivacaine compared with bupivacaine hydrochloride alone in patients who underwent knee replacement surgery.

Trial registration: isrctn.com Identifier: ISRCTN54191675.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hamilton reported receiving nonfinancial support in the form of investigational medicinal product from Pacira Pharmaceuticals Inc during the conduct of the study. Dr Knight reported receiving grants from the National Institute for Health Research (NIHR) Research for Patient Benefit (RfPB) program during the conduct of the study and grants from the NIHR for various clinical trials and funding streams outside the submitted work. Dr Cook reported receiving grants from the NIHR and nonfinancial support in the form of investigational medicinal product from Pacira Pharmaceuticals Inc during the conduct of the study. Dr Lamb reported receiving grants from the University of Oxford and University of Exeter during the conduct of the study. Dr Murray reported receiving grants from the NIHR RfPB program during the conduct of the study; grants from Zimmer Biomet related to knee replacement outside the submitted work; and holding a patent related to knee replacement with royalties paid from Zimmer Biomet. Dr Pandit reported receiving grants from the NIHR and Pacira Pharmaceuticals Inc; nonfinancial support in the form of investigational medicinal product from Pacira Pharmaceuticals Inc during the conduct of the study; personal fees from Pacira Pharmaceuticals Inc outside the submitted work; financial support from Zimmer Biomet, Medacta International, Smith & Nephew PLC, JRI Orthopaedics, Meril Life, Kennedys Law LLP, Invibio, DePuy Synthes, and Janssen Pharmaceuticals; and institutional financial support from Zimmer Biomet, DePuy Synthes, GlaxoSmithKline, Invibio, the NIHR, the UK-India Education and Research Initiative, and the Engineering and Physical Sciences Research Council. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Flow Diagram of Patient Enrollment, Randomization, and Follow-up
QoR-40 indicates Quality of Recovery 40; VAS, visual analog scale.
Figure 2.
Figure 2.. Marginal Mean Quality of Recovery 40 (QoR-40) Scores at Each Time Point
Error bars indicate 97.5% CIs. For numbers analyzed at each time point, see eTable 14 in Supplement 2.
Figure 3.
Figure 3.. Marginal Mean Pain Visual Analog Scale (VAS) Scores at Each Time Point
Error bars indicate 97.5% CIs. For numbers analyzed at each time point, see eTable 14 in Supplement 2.
See this image and copyright information in PMC

Comment in

References

    1. Price AJ, Alvand A, Troelsen A, et al. . Knee replacement. Lancet. 2018;392(10158):1672-1682. doi:10.1016/S0140-6736(18)32344-4 - DOI - PubMed
    1. Chan EY, Blyth FM, Nairn L, Fransen M. Acute postoperative pain following hospital discharge after total knee arthroplasty. Osteoarthritis Cartilage. 2013;21(9):1257-1263. doi:10.1016/j.joca.2013.06.011 - DOI - PubMed
    1. Lo LWT, Suh J, Chen JY, et al. . Early postoperative pain after total knee arthroplasty is associated with subsequent poorer functional outcomes and lower satisfaction. J Arthroplasty. 2021;36(7):2466-2472. doi:10.1016/j.arth.2021.02.044 - DOI - PubMed
    1. Malviya A, Martin K, Harper I, et al. . Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011;82(5):577-581. doi:10.3109/17453674.2011.618911 - DOI - PMC - PubMed
    1. Strickland LH, Kelly L, Hamilton TW, Murray DW, Pandit HG, Jenkinson C. Early recovery following lower limb arthroplasty: qualitative interviews with patients undergoing elective hip and knee replacement surgery. Initial phase in the development of a patient-reported outcome measure. J Clin Nurs. 2018;27(13-14):2598-2608. doi:10.1111/jocn.14086 - DOI - PubMed

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