Abstract
1. The more important literature of acute intoxication in man from the local anesthetics is reviewed, and cases are cited to show the close similarity between the symptoms produced in man and in the lower animals, especially the cat.
2. The phenomena of acute intoxication in the cat, following the intravenous injection of the local anesthetics, are described, and the similarity of the phenomena produced by different members of the group is emphasized.
3. The maximum toxicity for each of the members of the series has been determined by rapid intravenous injection in the cat, and the relative toxicities of the several drugs are represented graphically.
4. The several different local anesthetics are shown to be mutually and quantitatively synergistic, so far as their fatal actions are concerned.
5. The capacity of the cat to withstand the intravenous injection of several times the fatal vein dose of any of the local anesthetics, except cocain and holocain, has been shown by repeated injections of large doses, or the continuous injection of relatively dilute solutions.
6. The toxicity of the local anesthetics for the cat, after subcutaneous injection, has been shown to depend upon the ratio between the rate of absorption and that of elimination, and the local anesthetics can be divided into two classes with reference to that ratio. Five, or more than five, times the minimal fatal vein dose of alypin, apothesin, beta-eucain, nirvanin, procain, stovain and tropacocain can be injected subcutaneously in the cat without causing death, while four, or less than four, times the fatal vein doses of cocain and holocain similarly injected prove fatal.
7. The simultaneous subcutaneous injection of epinephrin with the local anesthetics materially reduces the toxicity of the latter by delay in the rate of their absorption, but this reduction is much less marked in the cases of cocain and holocain than with the other members of the series, and is referable to their much slower "essential" elimination.
8. The absorption of several of the local anesthetics from the mucous membranes of the nose and pharynx of the cat has been shown to be no more rapid than from the subcutaneous tissues, and the urethra, bladder and vagina resist the absorption of these drugs to a great extent.
9. The elimination of the local anesthetics in the cat has been demonstrated to be due to their rapid destruction by the liver, and this takes place in the excised, perfused organ as well as in the liver of the intact animal.
10. Various efforts have been made to influence the toxicity of the local anesthetics for the cat, and severe acute hemorrhage and narcosis by hydrated chloral alone seem to have any material influence. Both of these measures tend to increase the cat's susceptibility to the toxic actions of the local anesthetics, probably by diminishing the rate of their destruction in the liver through impairment of the circulation.
11. All of the local anesthetics have been shown to be synergistic with epinephrin on the blood pressure in a manner analogous to cocain.
12. The employment of artificial respiration, combined with stimulation of the heart by the intravenous injection of epinephrin, is capable of saving cats from death following the intravenous injection of as much as twice the average fatal dose of the local anesthetics.
13. Stimulation of the heart by the previous injection of ouabain permits the cat to recover from intravenous injections of nearly twice the average fatal dose of the local anesthetics, when the temporary paralysis of the respiratory center is combated by the use of artificial respiration.
14. The success of the last two measures depends upon the rapid destruction of the local anesthetics by the liver.
Footnotes
- Received June 3, 1919.
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