The Journal of Arthroplasty, Volume 33, Issue 1, 97 - 101

Systemic Safety of Liposomal Bupivacaine in Simultaneous Bilateral Total Knee Arthroplasty

Springer, Bryan D. et al.


Intraoperative periarticular injections (PAIs) with local anesthetic are an important component of multimodal pain control in total joint arthroplasty. Liposomal bupivacaine is an extended-release formulation of bupivacaine designed to provide extended pain relief, approved for use in a single surgical site. The systemic safety profile for use in simultaneous bilateral TKA (bTKA) with a full dose in each knee has not been evaluated. The purpose of this study was to determine the safety and pharmacokinetics of bilateral full-dose PAI liposomal bupivacaine in the blood collected in patients undergoing simultaneous bTKA.


In this prospective study, patients had an identical PAI consisting of 20 cc of liposomal bupivacaine (266 mg), 30 cc of 0.25% bupivacaine (75 mg) with epinephrine, and 10 cc of normal saline injected into each knee during bTKA. Blood samples were collected at predefined intervals until patient discharge. No exogenous bupivacaine was administered. Pharmacokinetic evaluations were subsequently performed and compared to bupivacaine toxicity levels. Patients were monitored for adverse events related to anesthetic toxicity (cardiac and neurologic).


Fifteen patients (mean age, 60.7 years; range, 57-64 years) were enrolled in the study. The mean peak level (Cmax) was 0.8 μg/mL (range, 0.4-1.2 μg/mL). All patients were well below the reported systemic cardiac and toxicity levels reported as 2-4 μg/mL. There were no reported cardiac and neurotoxic events in any patients.


The use of full-dose PAI with liposomal bupivacaine placed into each knee during simultaneous bTKA is safe with systemic bupivacaine levels well below reported cardiac and neurotoxic levels.

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