Comparative local anesthetic efficacy and pharmacokinetics of epidurally administered ropivacaine and bupivacaine in the sheep.

BACKGROUND AND OBJECTIVES: Ropivacaine is the S(-) propyl homolog of bupivacaine and mepivacaine. Studies in humans have confirmed the results of studies in laboratory animals that ropivacaine is a long-acting local anesthetic with an anesthetic profile similar to bupivacaine. Acute, intravenous systemic toxicity studies have been conducted in sheep and dogs. Local anesthetic efficacy has been studied after epidural administration in the dog. This study was initiated to determine the local anesthetic efficacy and pharmacokinetics of ropivacaine and bupivacaine after epidural administration in an experimental sheep model and to evaluate the sheep model as a model of experimental epidural anesthesia. METHODS: Twelve adult nonpregnant ewes were prepared with chronically implanted lumbar epidural catheters and arterial lines. Each sheep received injections of 5.0 mL ropivacaine and bupivacaine (0.5% and 0.75%) in a blinded, random, cross-over fashion. Onset and duration of sensory and motor blockade were evaluated. Arterial blood samples were drawn for serum drug concentration determinations and pharmacokinetic analysis. RESULTS: Onset and duration of motor blockade were similar for comparable concentrations of both drugs. Both concentrations of ropivacaine and bupivacaine 0.5% demonstrated differential neural blockade. The peak serum concentrations generally occurred within 8 minutes after administration. The terminal elimination half-life in serum was about 3.5-4.0 hours and 6 hours for ropivacaine and bupivacaine, respectively. No signs of systemic toxicity were observed. Results of sensory and motor blockade were consistent with previous studies in laboratory animals and humans. CONCLUSIONS: Ropivacaine produces sensory and motor blockade which is similar to that produced by equal concentrations of bupivacaine after epidural administration in the sheep. Peak serum concentrations produced no signs of systemic toxicity. The results of this study are consistent with previously published data from studies in laboratory animals and humans. The sheep model of experimental epidural anesthesia appears to be a clinically relevant method to evaluate experimental local anesthetics.

Antinociceptive and motor-blocking efficacy of ropivacaine and bupivacaine after epidural administration in the dog.

BACKGROUND AND OBJECTIVES: This study was initiated to evaluate the antinociceptive and motor blocking capabilities of epidurally administered 0.5% and 0.75% ropivacaine and bupivacaine using a blinded, random crossover design in the dog. Additionally, serum drug concentrations and serum protein binding were determined. METHODS: Twelve male beagles were prepared with chronic epidural and arterial catheters under sterile conditions. The epidural space was identified by a loss-of-resistance technique using an 18-gauge thin-wall Crawford needle via the midline approach. The catheter was attached to a Schraeder-type Teflon valve sutured subcutaneously. Local anesthetic drugs were administered into the lumbar epidural space in a constant volume of 3.0 mL. Evaluation of antinociceptive and motor blocking qualities were evaluated at regular intervals. Arterial blood samples were drawn during the 15 minutes following local anesthetic injection for drug concentration and pharmacokinetic analysis. RESULTS: Onset time of motor block in the ropivacaine 0.5% group was longer than in other groups but not significantly different. Duration of motor and sensory block demonstrated a dose-dependent relationship of both drugs. Bupivacaine 0.5% and 0.75% produced motor block (81 +/- 42 minutes and 198 +/- 44 minutes [mean +/- SD], respectively) of significantly longer duration than corresponding concentrations of ropivacaine (69 +/- 35 minutes and 133 +/- 32 minutes, respectively). The onset times for sensory block of the vertebral dermatomes were not different between groups. No difference was found in duration of dermatomal sensory block between the 0.5% solutions. However, the duration of dermatomal sensory block was significantly longer in the bupivacaine 0.75% group than in any other group. Peak arterial serum drug concentrations were not different between drugs at equal concentrations and were reached between 2 and 6 minutes in all animals. Both drugs were highly bound to serum proteins (> 98%). No severe adverse effects or sequelae were observed. CONCLUSIONS: The 0.5% solutions produced similar sensory block of the vertebral dermatomes. Duration of dermatomal block with 0.75% bupivacaine was longer than with the corresponding ropivacaine concentration. Ropivacaine produced motor block of shorter duration as compared with bupivacaine. Serum concentrations of the two drugs were similar after injection of the same doses. In this animal model, ropivacaine produced shorter durations of sensory and motor block than corresponding concentrations of bupivacaine. These data are consistent with previously published data in animals and humans.