A COMPARATIVE STUDY OF THE EXPERIMENTAL TOXICITY OF LOCAL ANESTHETIC AGENTS

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Abstract
Groups of rabbits were subjected to constant intraven. injn. of procaine, cocaine, tetracaine, and dibucaine at a rate which produces respiratory arrest in 8 min. The rate for procaine was 8 mg./kg./min.; for cocaine 2.75 mg./kg./min.; tetracaine 1 mg./kg./min.; dibucaine 0.35 mg./kg./min. From the point of view of respiratory arrest the toxicity ratio was procaine 1, cocaine 3, tetracaine 8, and dibucaine 20. Artificial respiration was then instituted and the injn. continued until cardiac arrest resulted, or in the case of tetracaine and cocaine, for a period of 20 min. With procaine cardiac arrest occurred in 37 min., with cocaine 12.8 min., with tetracaine 20 min., and with dibucaine 11.2 min. No animals recovered after cardiac arrest with dibucaine and all the animals receiving procaine recovered. Recovery with cocaine was 60% and with tetracaine, 40%. At the time of cardiac arrest cardiac massage was instituted for 3-4 min. to facilitate recovery. Five to 10 [mu]g./kg. of epinephrine intraven. were given when indicated at the point of impending cardiac failure. To study the rates of absorption on toxic reactions tetracaine and cocaine were adminstered topically to young albino rabbits by a catheter to the lungs, posterior nasal cavity and esophagus. Convulsions occurred rapidly and there was a high mortality with tetracaine indicating rapid intrapulmonic absorption. Intranasal tetracaine and cocaine intrapulmonically showed a much slower onset of convulsions. 1:25,000 or 1:50,000 epinephrine added to the tetracaine did not significantly retard the intrapulmonic absorption. Procaine and cocaine intoxications were benefited by pentobarbital, 20 mg./kg., whereas pentobarbital increased the potency of tetracaine causing respiratory arrest; however, the convulsive manifestations of tetracaine were controlled as with the other agents. Ten [mu]g./kg. of epinephrine intraven. stimulated well the cardiovascular system depressed by cocaine, procaine, and tetracaine, but in the case of dibucaine, little effect was produced.