Evaluation of the toxicity of local anaesthetic agents in man

Etidocaine given by intravenous infusion has been compared, using a double-blind technique, with bupivacaine and lignocaine in respect of toxic symptoms and signs. The degree of toxicity is affected considerably by the rate of drug infusion. At 10 mg/min subjects could tolerate twice the dose of etidocaine as bupivacaine. Tolerance to etidocaine was less at 20 mg/min but still compared favourably with bupivacaine at 10 mg/min. Considering the difference in potency of the two agents it was considered that the therapeutic ratios would not be substantially different. Lignocaine at 20 mg/min was better tolerated than etidocaine. Venous plasma concentration during these experiments showed a more rapid decrease in the case of etidocaine compared with bupivacaine, but the concentrations were unhelpful in predicting the toxic effects. Similarly electroencephalography revealed no abnormalities in spite of marked subjective and objective signs of toxicity.