Stefano Ricci
The success of the discovery of the effect of cocaine, announced in September 15th1 was so immediate that already the 11th of October 1884 a report on the event appeared on the New York Medical Record2 followed by Koller’s publication in Lancet.3
The community was stroked by the novelty, which was rapidly applied to other mucous membranes (nose, mouth, larynx, trachea, rectum and urethra). After one year more than 100 articles had been published in the scientific literature of Europe and America.4,5
In December 1884, at the New York Roosevelt Hospital Outpatient Department, William Halstead and his associates (R. Hall in particular) were able to obtain the block of the sensory nerves of the face and the arm;6 after repeated self-experimentation trials of the anesthetic power of the solution, they demonstrated that the anesthetic effect of cocaine could be transmitted to deeper structures, in all the parts of the body, through an injection who could block the transmission of the nervous sensation.2
In 1885 Halstead published his practical comments on the use and abuse of cocaine:7,8 based on the experience of more than 1000 of cases treated in local anesthesia at the Johns Hopkins Hospital. He submitted to publication very few other papers on the subject and his contribution to the development of local anesthesia was stated only in later years. However from unpublished data it is evident that many of the further evolutions: oral and dental local anesthesia; brachial plexus, posterior tibial nerve, pudendal nerve blocks; skin anesthesia with dilute solutions, prolongation of anesthetic effect reducing circulation rate.
Halstead is one of the most important surgeons of American medical history. He was able to hide, although not completely, the tragic event of becoming addicted to cocaine as a consequence of self-experimentation. It seems that he could obtain cocaine weaning, but at the price of a morphine dependence for the rest of the life. Many other colleagues involved in the initial experimentation experienced tragic cocaine addiction too.2,4
Carl L. Schleih, a German surgeon, suggested the possibility of administrating local anesthesia by direct tissues infiltration: he tested a diluted cocaine solution (1/2 gram × 1000 cc of saline) announcing at the Surgical Congress in Berlin (1892) that narcosis was no longer justified; his revolutionary idea was strongly rejected at that time.9
Broun, in 1900, demonstrated the efficacy of adrenaline association to anesthetic solutions for obtaining the chemical lace effect, in place of the elastic lace used till then, with the purpose of getting better effect and lesser toxicity.10
Spinal anesthesia, although promptly suggested by Corning,11 ought to wait 14 years to obtain a clinical application. In 1899 in Kiel, August Bier12 tried to inject cocaine through lumbar puncture in 6 patients obtaining a very poor anesthesia, but rather vomit and headaches. He decided then to experience personally the method allowing his assistant, Dr. Hildebrandt, to perform on him a lumbar injection (the assistant too received on turn the same treatment by Bier). Bier noted after 23 minutes: A strong blow with an iron hammer against the tibia was not felt as a pain. After 25 minutes: Strong pressure and pulling on a testicle were not painful.12 That night both complained a terrible headache which lasted 9 days, correctly ascribed to the spinal liquid leakage.13 The clinical use of spinal anesthesia will be developed slowly by the time, with the improvement of quality of the drugs and instruments.
Despite it's beneficial effects, cocaine evidenced heavy limits for the toxicity and the addition risks. In the first 7 years of its clinical use, at least 13 cases of death were reported.14 This strongly stimulated the search of an ideal substitute of cocaine; once discovered it's chemical structure (methyl- and benzoyl- ester of the alkaloid egconin), more than 100 compounds were tested, until procaine was found, by Einhorn in 1904.15 Procaine has been the synonymous of local anesthesia for nearly half a century due to its effectiveness, devoid from the toxic effects of cocaine.
In 1948 Löfgren and Lundquist, while studying the alkaloid gramine, succeeded in synthesizing lidocaine which turned out to be strong, stable, rapidly diffusing in tissues, with low toxicity.16 All the local anesthetic agents subsequently developed trying to enhance the effectiveness and reduce the collateral effects (mepivacaine, bupivacaine, ropivacaine) belong to this chemical family.
Differently from cocaine, all the local anesthetic agents are devoid from potential habituation.
The clinical demand of agents fit to achieve trans-dermal anesthesia brought to the development (1994) of a cream, EMLA (acrostic of eutetic mixture of lidocaine and prilocaine), based on an emulsion oil-in-water of two anesthetic agents. Inside the small drops of the emulsion a very high concentration of the agents is present , while the overall concentration is very low.17 The maximum depth of anesthesia achievable is approximately 5 mm, very interesting for superficial skin lesions and limited superficial surgery.
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