A RABBIT MODEL FOR THE EVALUATION OF EPIDURALLY ADMINISTERED LOCAL-ANESTHETIC AGENTS

A rabbit model is described for the evaluation of epidurally administe red local anaesthetic agents. The technique involves a single injectio n via the readily identified lumbosacral space in conscious rabbits, w ith the epidural space being identified by a modified loss-of-resistan ce technique. The endpoints used to assess pharmacodynamic responses o f the rabbit model were (1) sensory loss, (2) loss of weight-bearing a bility, and (3) flaccid paresis. The model was further characterised b y investigation of endpoint responses to changes in injection volume ( 0.1-0.25 ml/kg) and concentration of administered lignocaine solutions (0.5 to 2%). From these studies, a volume of 0.2 ml/kg was chosen as a standard dose and a subsequent comparison between different agents u ndertaken. The rank order for the onset of action, duration of effect and the observed pharmacokinetic profiles after epidural administratio n of 2% lignocaine, 2% lignocaine with adrenaline (1:200,000) or 0.5% bupivacaine solutions are broadly consistent with human clinical data. These data indicate that the rabbit is a simple (albeit limited) mode l for the screening evaluation of epidurally administered local anaest hetic agents.