Comparative systemic toxicity and a mechanism for lethality of intravenously infused cocaine, lidocaine, and bupivacaine in spontaneously and mechanically breathing unconscious pigs

We investigated systemic toxicity and possible mechanisms for lethality of intravenously (iv) infused cocaine (C), lidocaine (L), and bupivacaine (B) in 24 spontaneously and mechanically breathing unconscious pigs. Pigs were given sodium thiopental and ventilated with 70% nitrous oxide in 30% oxygen. Pigs in groups 1, 2, and 3 pigs were allowed to breathe spontaneously and groups 4, 5, and 6 were mechanically ventilated. The animals in groups 1 and 4 were infused iv with C (0.8 mg/kg/min), groups 2 and 5 were infused with B (0.8 mg/kg/min), and groups 3 and 6 were infused with L (3.2 mg/kg/min). Respiratory and cardiovascular parameters, blood temperature, sodium and potassium levels were monitored. The times of occurrences of respiratory (RA) and cardiac arrests (CA), and convulsions were recorded. Our results showed that RA is the primary cause of death in spontaneously breathing pigs and that mechanical ventilation significantly delayed the occurrence of CA (p < 0.05). Significant decreases in cardiac output, mean blood pressure, and heart rate and significant increases in systemic and pulmonary vascular resistances, central venous and pulmonary wedge pressures, and blood K⁺, levels were noticed in mechanically ventilated pigs (p < 0.05). Our experiments demonstrated that all three local anesthetic drugs produced similar systemic effects with continuous iv administration of lethal doses.