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.

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Chronotropic and inotropic effects of ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated, perfused rabbit heart.

BACKGROUND AND OBJECTIVES: The purpose of this study was to compare the inotropic and chronotropic effects of ropivacaine, bupivacaine, and lidocaine in an isolated, spontaneously beating rabbit heart preparation. The ability to electrically pace the heart in the presence of local anesthetic also was examined. METHODS: Hearts were perfused with Krebs-Henseleit solution, then exposed to ropivacaine or bupivacaine at 1, 6, or 13 micrograms/ml or lidocaine at 6, 20, or 40 micrograms/ml (n = 6, each concentration). Left ventricular pressure, left ventricular dP/dt (rate of change derivation from analog waveform of the left ventricular pressure wave), pulmonary artery flow, oxygen consumption, and electrocardiogram were monitored throughout the studies. Drug exposure was for 30 minutes or until a 75% decrease in left ventricular pressure occurred. RESULTS: All preparations were exposed to 1 microgram/ml bupivacaine or ropivacaine and 6 micrograms/ml lidocaine for the full 30 minutes. At the intermediate concentrations, only one of six bupivacaine preparations (6 micrograms/ml) survived the full 30-minute exposure period, compared to six of six preparations for both ropivacaine (6 micrograms/ml) and lidocaine (20 micrograms/ml; p less than 0.05). Similar results were found with exposure to the highest concentrations of these local anesthetics. No electrocardiogram changes were observed with any of the three lidocaine concentrations or with the lowest ropivacaine and bupivacaine concentration. At the intermediate concentration, atrioventricular conduction changes were seen with bupivacaine in five of six preparations, compared to one of six ropivacaine preparations (p less than 0.05). With the high concentration, ventricular tachycardia occurred in four of six bupivacaine preparations, compared to zero of six with ropivacaine (p less than 0.05). In general, left ventricular systolic pressure, dP/dt, heart rate, and oxygen consumption were reduced during exposure to all concentrations of the three local anesthetics. The most profound effects (greater than 75% reduction) were seen with 13 micrograms/ml bupivacaine. All local anesthetics caused an increase in the voltage required to pace the hearts via the atria. With 6 micrograms/ml bupivacaine and 13 micrograms/ml ropivacaine, 50% of the preparations could not be paced via the atria; and with 13 micrograms/ml bupivacaine, none of the preparations could be paced via the atria. The depressant effects of 6 micrograms/ml bupivacaine approximated those seen with 13 micrograms/ml ropivacaine. The reductions in oxygen consumption and pulmonary artery flow were not significantly different between treatment groups. CONCLUSION: The results of this study indicate that bupivacaine is more cardiodepressant and arrhythmogenic than either ropivacaine or lidocaine.

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The effects of epinephrine on the anesthetic and hemodynamic properties of ropivacaine and bupivacaine after epidural administration in the dog.

Ropivacaine is a new local anesthetic that is chemically related to mepivacaine and bupivacaine. Previous laboratory studies have demonstrated that ropivacaine possesses an anesthetic profile similar to that of bupivacaine and has less arrhythmogenic potential. The current study was initiated to compare the hemodynamic and anesthetic effects of epidurally administered 0.75% bupivacaine and 1% ropivacaine, with and without epinephrine (1:200,000), in the dog. Two groups of six dogs were randomly assigned to the ropivacaine or bupivacaine treatment groups. Administration of 0.75% bupivacaine and 1% ropivacaine with and without epinephrine was randomized. Volumes of 3 ml of each solution were injected in a blinded manner via an indwelling lumbar epidural catheter with 48 hours between injections. No statistically significant difference existed between the four treatment groups with regard to onset and duration of sensory or motor block. Hemodynamic changes were, for the most part, not different between drugs. Significant decreases were seen in mean arterial blood pressure and cardiac output in all test groups. No difference in the degree of cardiovascular depression was observed. The addition of epinephrine did not alter onset or duration of sensory or motor block in this animal model. Epinephrine reduced the average anesthetic blood concentration observed in both treatment groups at the various time intervals, but not the time to achieve the mean maximum blood level. No residual adverse effects were observed in any animal.

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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.

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