Background

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

Methods

Volunteers aged 18 to 55 yr (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 or more, 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.

Results

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

Conclusions

The 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.

Editor’s Perspective
What We Already Know about This Topic
  • Liposomal bupivacaine is a bupivacaine formulation developed with the goal of providing long-lasting regional analgesia
  • Because it is recommended that liposomal bupivacaine be used in combination with plain bupivacaine, its intraoperative and immediate postoperative potency when used alone are poorly understood
What This Article Tells Us That Is New
  • The hypothesis that the pharmacodynamic characteristics of liposomal bupivacaine do not differ from those of plain bupivacaine during the initial period after administration but are better long term was tested in a randomized, controlled, triple-blinded crossover study in 25 volunteers
  • Liposomal bupivacaine produced surgical blockade, defined as no sensory response upon pinprick testing, in 32% of volunteers; plain bupivacaine produced surgical blockade in all volunteers
  • Compared to plain bupivacaine, liposomal bupivacaine sensory blockade began later and did not last as long
  • Despite being described as an extremely long-acting bupivacaine formulation, liposomal bupivacaine produced unpredictable intermittent patterns of residual blockade