Wound infiltration with liposomal bupivacaine prolongs analgesia in rats

Background: Wound infiltration with local anesthetics does not reliably produce satisfactory postoperative analgesia, and the dose of local anesthetic which may be safely administered is limited by the potential for systemic toxicity. This study evaluated the efficacy of a slow-release liposomal bupivacaine formulation on duration of wound analgesia.
Methods: Multilammelar liposomes containing bupivacaine were assessed using a rat paw wound model. Twenty-four hours after surgical incision, paw wounds determined to be hyperalgesic to graded force testing with von Frey hairs were infiltrated with 0.3 ml of 2% liposomal bupivacaine, 0.5% plain bupivacaine, saline, or 'empty' (normal saline) liposomes (n=6/group). The duration of analgesia was measured. The 0.5% plain concentration was chosen because, in preliminary experiments, larger doses were often fatal. Analgesia duration was compared using Mann-Whitney U test at P < 0.05. In other rats, plasma bupivacaine levels after wound infiltration with either 2% liposomal formulation or 0.5% plain formulation were assessed (n=8/group).
Results: The mean duration of analgesia was 23+/-3 (SD) min for plain bupivacaine and 180+/-30 min for liposomal bupivacaine. No wound analgesia was detected in animals given normal saline or 'empty' liposomes. Plasma bupivacaine levels tended to be lower after liposomal than plain bupivacaine.
Conclusions: The 8-fold increase in duration of wound analgesia and the lower plasma levels seen with the liposomal formulation are explained by gradual drug release from the liposomal depot. These results may have important implications for achieving safe and effective analgesia with wound infiltration techniques in humans.