Importance: Over half of patients report significant acute post-operative pain following knee replacement.
Objective: To evaluate the clinical and cost effectiveness of peri-articular liposomal bupivacaine (LB) for recovery and pain following knee replacement.
Design, Setting and Participants: This multi-centre, patient-blinded, pragmatic, randomized controlled superiority trial (RCT) 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 29th, 2018 and February 29th, 2020 and followed up for one year after surgery.
Interventions: LB (266mg) admixed with bupivacaine hydrochloride (100mg) compared to bupivacaine hydrochloride (100mg) alone (control) administered by peri-articular injection at the time of surgery.
Main Outcome and Measures: The co-primary outcomes were Quality of Recovery 40 (QoR-40) score at 72hours and pain visual analogue score (VAS) area under the curve (AUC) 6 to 72hours. Secondary outcomes included: QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2 and 3, cumulative opioid consumption over 72hours, functional outcomes and quality of life at 6weeks, 6months and 1year, and cost-effectiveness over 1year. Adverse Events and Serious Adverse Events up to 12months post-randomization were also assessed.
Results: 533 participants, mean age 69years were randomized with baseline characteristics balanced between arms. There was no difference in QoR-40 at 72hours nor pain VAS AUC 6 to 72hours between LB and control arm (adjusted mean difference for QoR-40: 0.54 (97.5% CI -2.05 to 3.13, p=0.643); pain VAS AUC -21.5 (97.5% CI -46.8 to 3.8; p=0.057)). Analyses of pain VAS and QoR-40 scores demonstrated only one statistically significant difference, with the LB arm having lower pain scores the evening of surgery (day 0; adjusted difference -0.54, 97.5% CI - 1.07 to -0.02; p=0.021). No difference in cumulative opioid consumption and functional outcomes was detected. LB was not cost-effective compared to control. No difference in adverse or serious adverse events was found between LB and control arms.
Conclusion and Relevance: This study found no difference in post-operative recovery associated with the use of peri-articular LB compared to bupivacaine hydrochloride alone. This study does not support the use of peri-articular LB for knee replacement.
Trial Registration: ISRCTN 54191675, registered on 14 November 2017. http://www.isrctn.com/ISRCTN54191675
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)