COMPARATIVE SYSTEMIC TOXICITY OF ROPIVACAINE AND BUPIVACAINE IN NONPREGNANT AND PREGNANT EWES

Background: Ropivacaine is a new amide local anesthetic, having therap eutic properties similar to those of bupivacaine but with a wider marg in of safety. Bupivacaine is probably the most commonly used drug in o bstetric epidural analgesia, even though laboratory studies have sugge sted that pregnancy increases the cardiotoxicity of bupivacaine but no t of other local anesthetics. The current study was designed to reeval uate, in a random and blinded fashion, the systemic toxicity of bupiva caine and ropivacaine in nonpregnant and pregnant sheep.Methods: Chron ically prepared nonpregnant and pregnant ewes were randomized to recei ve an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg . kg(-1) . min(-1) until circulatory collapse. The inv estigators were blinded to the identity of local anesthetic. Heart rat e, arterial blood pressure, and cardiac rhythm were monitored througho ut the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood p H and gas tensions were measured. Results: There were no significant d ifferences between nonpregnant and pregnant animals in the doses or se rum concentrations of either drug required to elicit toxic manifestati ons. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convuls ions and circulatory collapse, In pregnant ewes, greater doses of ropi vacaine as compared to bupivacaine were required to produce convulsion s (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg . kg(-1)) and circulatory collapse ( 12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg . kg(-1)). The corresponding serum con centrations of ropivacaine were similar to those of bupivacaine. Pregn ancy did not affect the serum protein binding of either drug. The prop ortion of animals manifesting a malignant ventricular arrhythmia as th e terminal event was similar among all groups. Conclusions: The system ic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep, This is in contrast to an earlier study in which the cardio toxicity of bupivacaine was enhanced during ovine pregnancy, Greater d oses of ropivacaine, as compared to bupivacaine, are needed to produce toxic manifestations in pregnant animals.