Comparative Systemic Toxicity of Convulsant and Supraconvulsant Doses of Intravenous Ropivacaine, Bupivacaine, and Lidocaine in the Conscious Dog

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Abstract
Tics. On the first experimental day, lidocaine (8 mg·kg−1 · min−1), bupivacaine (2 mg·kg−1·min−1), and ropivacaine (2 mg·kg−1·min−1) were infused intravenously until seizures occurred (n = 6 for each group). The average dose and arterial plasma concentration at seizure onset was 20.8 ± 4.0 mg/kg and 47.2 ± 5.4 μg/ml for lidocaine, 4.31 ± 0.36 mg/kg and 18.0 ± 2.7 μg/mL for bupivacaine, and 4.88 ± 0.47 mg/kg and 21.4 ± 0.9 μg/mL for ropivacaine. The margin of safety between the convulsive and lethal doses was determined by administering two times the convulsive dose 24 h later. Two dogs given lidocaine died because of progressive hypotension, respiratory arrest, and finally cardiovascular collapse with an average peak plasma concentration (Cmax) of 469 μg/mL. No ventricular arrhythmias were observed in this group. Ventricular arrhythmias occurred in five of six dogs receiving bupivacaine. Four animals died because of hypotension, respiratory arrest, and cardiovascular collapse. One additional animal died because of ventricular fibrillation. The Cmax for bupivacaine was 70.1 ± 14.6 μg/mL in nonsurvivors. In the ropivacaine group one animal died because of hypotension, respiratory arrest, and cardiovascular collapse (Cmax 72.4 μg/mL). A surviving dog had transient premature ventricular contractions. Twenty-four hours later three times the convulsive dose was administered to the survivors. Death occurred in three animals in the lidocaine group, the remaining dog in the bupivacaine group, and four dogs in the ropivacaine group. All deaths were due to hypotension, respiratory arrest, and subsequent cardiovascular collapse. Ventricular arrhythmias were observed in two dogs in the ropivacaine group and the single dog receiving bupivacaine. The results suggest that the convulsive doses for ropivacaine and bupivacaine are similar. However, ropivacaine may possess a greater margin of safety and be less arrhythrnogenic than bupivacaine after an accidental rapid IV injection. Only lidocaine was devoid of arrhythmogenic activity. Address correspondence to Mr. Feldman, Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. Supported in part by a grant from ASTRA Pain Control, Sodertalje, Sweden. The authors thank Ann Marie Doucette and Sally B. Norway for their excellent technical assistance and Rachel Abrams for typing the manuscript. Accepted for publication July 31, 1989. © 1989 International Anesthesia Research Society...

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