The acute intravenous cardiovascular toxicity of three amino-ester local anesthetic agents was studied in the pentobarbitalized, ventilated dog. Significant depression of mean arterial blood pressure, heart rate, cardiac output and stroke volume was observed at 10 mg/kg of tetracaine, while insignificant changes were seen after the same dose of procaine and chloroprocaine. At 30 mg/kg there was minimal depression of cardiovascular parameters with procaine, whereas this same dose of chloroprocaine proved to be lethal. Myocardial depression appeared to be primarily responsible for the profound cardiovascular depression since minimal changes in peripheral vascular resistance occurred until a lethal dose was administered. Increases in mean pulmonary artery pressures and pulmonary vascular resistance were observed prior to the development of myocardial depression which suggests a direct pulmonary vasoconstrictor effect.
The cumulative lethal dose was approximately 30 mg/kg for tetracaine, 60 mg/kg for chloroprocaine, and 230 mg/kg for procaine. The cardiovascular toxicity of these agents appears to be proportional to their anesthetic potency rather than their rate of hydrolysis when administered as an intravenous bolus which mimics the clinical situation of an inadvertent intravascular injection.
- Cardiovascular toxicity
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Supported in part by a grant from Breon Laboratories Inc, New York.
Address reprint request to Dr. Liu: Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.