WOUND INFILTRATION WITH LIPOSOMAL BUPIVACAINE PROLONGS ANALGESIA IN RATS

Background: Wound infiltration with local anesthetics does not reliabl y produce satisfactory postoperative analgesia, and the dose of local anesthetic which may be safely administered is limited by the potentia l for systemic toxicity. This study evaluated the efficacy of a slow-r elease liposomal bupivacaine formulation on duration of wound analgesi a. Methods: Multilammelar liposomes containing bupivacaine were assess ed using a rat paw wound model. Twenty-four hours after surgical incis ion, paw wounds determined to be hyperalgesic to graded force testing with von Frey hairs were infiltrated with 0.3 mi of 2% liposomal bupiv acaine, 0.5% plain bupivacaine, saline, or 'empty' (normal saline) lip osomes (n = 6/group). The duration of analgesia was measured. The 0.5% plain concentration was chosen because, in preliminary experiments, l arger doses were often fatal. Analgesia duration was compared using Ma nn-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 duratio n of analgesia was 23+/-3 (SD) min for plain bupivacaine and 180+/-30 min for liposomal bupivacaine. No wound analgesia was detected in anim als given normal saline or 'empty' liposomes. Plasma bupivacaine level s tended to be lower after liposomal than plain bupivacaine. Conclusio ns: The 8-fold increase in duration of wound analgesia and the lower p lasma levels seen with the liposomal formulation are explained by grad ual drug release from the liposomal depot. These results may have impo rtant implications for achieving safe and effective analgesia with wou nd infiltration techniques in humans. (C) Acta Anaesthesiologica Scand inavica 41 (1997).