The Comparative Toxicity of Ropivacaine and Bupivacaine at Equipotent Doses in Rats

Abstract

We compared the toxicity of systemic local anesthetics bupivacaine and ropivacaine administered at equivalent and equipotent doses. In the first experiments, 18 male Wistar rats were anesthetized with thiopental and maintained under positive controlled ventilation. Electrocardiogram, electroencephalogram, and invasive arterial blood pressure were continuously recorded. The animals were randomly assigned to receive 3 mg x kg(-1) x min(-1) bupivacaine, 3 mg x kg(-1) x min(-1) ropivacaine IV (equivalent group), or 4.5 mg x kg(-1) x min(-1) ropivacaine (equipotent group). The timing of the occurrence of local anesthetic-induced toxic events (defined as the first QRS modification, dysrhythmia, seizures, moderate and severe bradycardia and hypotension, final systole) was recorded and the dose calculated. Eighteen additional rats, treated according to the same protocol were killed at the time of moderate, severe, and final hypotension for blood sampling and plasma bupivacaine and ropivacaine concentration measurement. In a third experiment, 15 awake rats (5 per group) received IV bupivacaine or ropivacaine (same infusion as in the first experiments) until seizure. At this moment, rats were allowed to recover from local anesthetic intoxication. In the first experiment, except for the first QRS modification, all the other toxic manifestations occurred at significantly larger doses (P<0.05) in the two ropivacaine groups in comparison to the bupivacaine group. In awake rats, all the animals intoxicated by ropivacaine easily recovered. In the bupivacaine group, two animals required cardiopulmonary resuscitation before any seizure activity could be detected, and only three rats survived. We conclude that, in the model used, ropivacaine, even at an equipotent dose, is less toxic than bupivacaine.