Systemic toxicity of ropivacaine during ovine pregnancy

Abstract

Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg·kg-1·min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order - convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestation. For example, circulatory collapse occurred at a mean dose of 11.3 ± 1.1 mg·kg-1 in nonpregnant and 12.4 ± 0.9 mg·kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 ± 0.3 and 9.6 ± 2.1 μg·ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.