/"he JO URNAL OF THE FRANKLIN INSTITUTE OF THE STATE OF PENNSYLVANIA DEI"OTED 7"0 SCIENCE AND THE MECHANIC ART8 VOL. CLXXII AUGUST, I9II No. 2 THE CHEMISTRY O.F ANZESTHETICS.* BY CHAS. BASKERVILLE, Ph.D., F.C.S., Professor of Chemistry, College of the City of New York. SACRED, profane and mythological literature abound in inci- dent, fact and fancy, showing that from earliest times man has sought to assuage grief and pain by some means of dulling con- sciousness. Recourse was had to the inhalation of fumes from various substances, weird incantations, applications of drugs, both external and internal, pressure upon important nerves and blood- vessels, and the laying on of hands, or animal magnetism. Each has played its part in the mitigation of human ills. It was not until the close of the eighteenth century~ however, that modern surgical anaesthesia was foreshadowed. Then it was that the dis- covery of hydrogen, nitrogen, oxygen, and nitrous oxide pneu- matic chemistry, as it were--created a field of pneumatic medi- cine. In I798, the Pneumatic Institute was founded for the pur- pose of investigating the "medical powers of factitious airs or gases " and was set up at Clifton by Dr. Thomas Beddoes. The immediate idea to be followed out was the treatment of phthisis and other lung troubles by inhalation of various gases. Hum- phrey Davy was assigned the omce of superintending the experi- * Presented Wednesday evening, June 14, 1911. [NoTE.--The Franklin Institute is not responsible for the statements and opinions advanced by contributors to the JOURNAL.] Copyright, x9l t, by THE PRANKLIN INSTITUTR. VOL. CLXXII, No. 1028-"--9 113 I 14 CHAS. BASKERVILLE. ments. One of the first outcomes of his researches, the result of his experimentation with nitrous oxide upon animals, is given in the following historical and often quoted sentence1 : " As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used to advantage during surgical operations in which no great effusion of blood takes place." Davy actually inhaled the gas, and recorded his own sensations and the behavior of others after they had in- haled it. In ~8o 5 Dr. Warren, of Boston, used " sulphuric ether " on a patient suffering with phthisis, and the year following it was used in attacks of asthma; but Faraday in I818 was the first to recognize its value as an anaesthetic. Chloroform was discovered in I83I independently by Liemg, Soubeiran and Guthrie. It is reported in the American Journal of £cience for January, I832, that Dr. Ires, of New Haven, used chloroform in surgery. In I828, Girardin read a paper describing surgical anmsthesia by means of inhaled gases ; but the honor of the discovery, of sur- gical anaesthesia has been claimed, with more or less acrimonious partizanship, for four others, namely, Long, of Jefferson, Ga., who anaesthetized a patient with ether in I84I ; Wells, of Hart- ford, Conn., who used nitrous oxide in dentistry in ~844; and Morton, a pupil of Wells, used ether instead, at the suggestion of Jackson, a chemist, who later claimed to be the real dis- coverer. Simpson, in I847, first used ether in midwifery and later he employed chloroform, whose an,esthetic properties had been previously descrit)ed by Flourens. In I868 Andrews, of Chicago, called attention to the use of oxygen with nitrous oxide to produce a non-asphyxial form of anaesthesia. In I9o6, Brown, of Cleveland, used a warmed mixture of nitrous oxide and oxygen, followed by ether and chloroform, with great suc- cess. In i9o 9, Gwathmey, of New York, moistened the gases. I need not recount the historical data which have to do with other anaesthetics, a list of which I have published in the American Druggist, and my remarks this evening will therefore be limited to nitrous oxide, ether and chloroform: and these ~Davy "Researches, Chemical and Philosophical, chiefly concerning Nitrous Oxide," London, i8oo. THE CHEMISTRY OF AN.ESTHETICS. II 5 few facts--the results obtained from careful unbiased investi- gation of the literature and other forms of evidence--are given without elaboration or argument. The writer knows of rio satisfactory basis of classification of anaesthetics. Some are general, others local, but the latter may become general in their effects, depending upon conditions. Hence, they will be considered in chronological order. NITROUS OXIDE. In 1772, Priestley first prepared nitrous oxide by reducing NO with moist iron filings. In 1793, Deiman and others pre- pared the gas by heating NH4NO~, essentially the commercial process for its manufacture to-day. It is usually carried out by heating mixed salts, as NaNO~ and (NH4)2SO4, NaNO3 and NH4C1, etc. 2 Commercial nitrous oxide is apt to contain these impurities: C12, NO, NO2, HNO3, NH~, HC1, CO., O2, N2, and the rare gases of the air. It is usually purified by passage through solu- tions of sodium hydroxide, ferrous sulphate, and sulphuric acid. Further purification may be accomplished by the formation of a hydrate 3 below 0 ° C. and heating this hydrate (N20,6H2'O)-- that is, by fractional condensation 4 and by fractional distillation. The following impurities may be suspected in a cylinder of compressed nitrous oxide: i. Solids. 2. Liquids. 3. Gases and vapors: H._,O, halogen acids, HNO3, organic acids, 0~, NO2, N~03, SO~, •NH3, organic bases, CO~., halogens, oxides of chlorine, HCN, (CN):, PH3, SbH,, ASH3, H~S, 02, H2, CO, CH4, organic matter (from valve lubricants), N2, rare gases of the air. Baskerville and Stevenson, I. Ind. and Eng. Chem., iii, No. 8. s Villard, Compt. rend. (I894), cxviii, lO96. Stolzenberg, Ber., xliii, 17o8. I I6 CtlAS. BASKERVILLE. For these impurities, a qualitative search should first be made and ~then, whenever necessary, a quantitative determination. A systematic procedure has been devised, a detailed account of which on this occasion would be unwelcome. Those substances known to be irritant to the respiratory organs should be tested for to make sure of their absence before the gas is used in sur- gical cases. It may be said that established manufacturers appre- ciate this and govern themselves accordingly, consequently it is not necessary to test every cylinder supplied by them. Their integrity constitutes an asset--a fact which, unfortunately, is not the case with all manufacturers of all drugs. Beyond the absence of disturbing impurities, the improved methods of the use of nitrous oxide for anaesthetic purposes de- TABLE I. ANALYSIS. i N~,ete N~Obyl N~Oby [N2Oby No.] N,O H~O CO2 NHs 02 by explo- Cu + CO~ [ Cu -- ai~. S!O~_ +~;__] m ! x / 99.7 I °'I3 I o o.oo6 present / o.16 97.5 ! 99.4 / 99-7 I 96"6 I °'15 I o o.oo i present / 3"25 / 95 .0 ! 96.2 ~ 9''0 3 | 99.5 h °'I5 / o o present / o.35 I97.3 I 99.5 ~ 9~.5 4195"9 /°'I6/ present o present /394194II 95.6 19.~0 mand a knowledge of the approximate content of nitrous oxide in the commercial product, as will become apparent later; hence a method for its determination is desirable. Various methods have been proposed--for instance, decomposition into N2 and 02, burning with hydrogen, explosion with hydrogen, combustion of charcoal with absorption of CO2 produced, explosion with CO, oxidation of a fused mixture of sodiuln carbonate and Cr~O3 and determining the amount Of Na2CrO4 produced, and absorption in alcohol; and none is satisfactory. Dr. Stevenson and the writer have devised a new method, which gives accurate results in hands skilled in the manipulation of gases. It depends upon passing a definite quantity of the gas over heated copper gauze, after a preliminary treatment to remove oxygen or compounds which produce copper oxide from the sample, and then passing hydrogen through the apparatus, and absorbing the water formed. THE CHEMISTRY OF ANAESTHETICS. 11 7 Table I, which is self-explanatory, exhibits the results of our analyses of compressed nitrous oxide as supplied by American manufacturers. Nitrous oxide which is-: to be used for anaesthesia, should contain at least 95 per cent. of N20 and no solids, liquids, com- bustible organic matter, chlorine, or other oxides of nitrogen. A small amount of carbon dioxide, according to the investigations of Gatch, can have no evil effects. If present, however, the per- centage should be known. ETHYL ETHER. Experiences of expert anaesthetizers, often not accounted for by idiosyncrasy, obtained in the use of ethyl ethers supplied by various manufacturers in numerous surgical cases, furnished the motive for this phase of the investigation of the chemistry of anaesthetics. The standards laid down by the various pharma- copoeias of the world are not uniform. In view of that fact alone, a thorough investigation seemed called for. Enquiries addressed • to large consumers of the solvent in manufacturing processes adduced further need for satisfactory methods of determining the purity of ethyl ether and of detecting impurities introduced, or proving their absence if eliminated, in the modification of raw products used in its manufacture. The presence of small amounts of substances has oftentimes been the cause of a chemical reaction proceeding in a particular direction by virtue of a " catalytic action." So the presence of even traces of certain substances, as peroxidized compounds, aldehyde, etc., may have caused some reactions to be incorrectly explained, or to follow an unusual, or unaccounted for, route. Ethyl ether is still made commercially by the historical process of treating alcohol with sulphuric acid--hence the misnomer of " sulphuric ether," or " vitriolic ether "--although other synthetic processes have been proposed, some of which have been tried out.