Little is known about the pharmacodynamic characteristics of liposomal bupivacaine. Hypothesizing that we would not identify pharmacodynamic differences from plain bupivacaine during the initial period after administration, but would find better long-term pharmacodynamic characteristics, we designed a randomized, controlled, triple-blinded, single-center study in volunteers.


Volunteers aged 18 to 55 years (body mass index: 18 to 35 kg/m²) received two ulnar nerve blocks under ultrasound guidance. Using a crossover design with a washout phase of ≥ 36 days, one block was performed with liposomal and one with plain bupivacaine. Which came first was determined by randomization. Sensory data were collected by pinprick testing and motor data by thumb adduction, either way in comparison with the contralateral arm. Endpoints included success, time to onset, and duration of blockade. Residual efficacy was assessed by the volunteers keeping a diary. Statistical analysis included Wilcoxon signed-rank and exact McNemar’s tests, as well as a generalized estimation equation model.


Successful sensory blockade was noted in 8/25 volunteers (32%) after liposomal and in 25/25 (100%) after plain bupivacaine (P < 0.0001). Significant differences emerged for time to onset, defined as 0% response to pinpricking in 4/5 hypothenar supply areas (P < 0.0001), and for time from onset to 80% or 20% in 1/5 areas (P < 0.001; 0.001). Carry-over effects due to the randomized sequencing were unlikely (estimate: −0.6286; SE: 0.8772; P = 0.474). Self-assessment over 3.5 days did reveal, for liposomal bupivacaine only, intermittent but unpredictable episodes of residual sensory blockade.


Our results show that liposomal bupivacaine is not a suitable ‘sole’ drug for intraoperative regional anesthesia. Findings of its limited long-term efficacy add to existing evidence that a moderate effect, at best, should be expected on postoperative pain therapy.