August 15, 1907] 



NA TURE 



403 



Occasional attempts have been made in the past — by 

 Snow ' first of all, by the French school of physiologists, 

 Paul Ijert,^ Grehant," Dubois, ■■ and others, more recently 

 by committees of medical societies and o( the British 

 Medical Association ' — lo determine what may be desig- 

 nated as the physiological arithmetic of chloroform ; but 

 partly bv reason of the difficulty in the way of measuring 

 percentages of chloroform in the air and in the blood, 

 partly bv reason of the facility with which chloroform can 

 be administered without any reference to percentages, the 

 results obtained . produced ' very little impression upon 

 clinical practice, and deaths that could not have occurred 

 it the principles laid down by Snow and by Bert had 

 been properly appreciated and 'acted upon, were and still 

 are regarded by the medical profession and by the public 

 as the normal incidents of medical practice, and attributed 

 to anv but their true cause — an overdose of chloroform. 



I shall not venture to guess at the number of avoidable 

 deaths that have taken place from this cause, but 1 place 

 before you a diagram constructed from the annual returns 

 of Somerset House and giving the number of deaths 

 olVicially classified under the heading " An;csthetics " 

 during the last fifty years. I do not wish to use the 

 diagr.im in an alarmist sense, so I hasten to call your 

 attention to the fact that the numbers are not percentages, 

 but absolute figures, which may in your opinion be 

 sutiiciently accounted for by the fact that the absolute 

 number of cases has augmented in which anaesthetics have 

 been employed, and that official returns of fatal cases 

 mav have become more complete. 



Indeed, I do not myself base my judgment of the matter 

 so much upon statistics, w'hich are notoriously apt to be 

 imperfect and misleading, as upon the common experience 

 of most members of the medical profession and of many 

 persons outside that profession ; I have rarely met a well- 

 informed person who was not personally acquainted with 

 at least one accidental death by chloroform. Nevertheless 

 I have presented to you the above statistical diagram 

 because 1 consider that with due reservation this outcome 

 of unprejudiced observation gives a by no means ex- 

 aggerated picture of an actual fact, and because I believe 

 it' is an avoidable fact and will be diminished in future 

 years by the wider knowledge of the physiology of 

 anaesthesia. 



I hope I shall not tax your attention too severely if 

 I ask vou to follow me through a short arithmetical 

 argument in order to convince you that accidental deaths 

 by chl.roform must of necessity be expected to occur in 

 the ort'inarv wav of administration if the administrator is 

 not fu'lv alive to the physical and physiological properties 

 of chl.iroform, and to outline in your minds a definite 

 picture of some very simple and important measurements. 



By ordinary methods of administration the percentage 

 of chkroform vapour in the mixture of chloroform and 

 air inhaled may be anything between i and lo per cent. ; 

 let us sav that it is 4 per cent. — i.e., that an inhalation 

 of, say, 500 c.c. carries 20 c.c. of chloroform vapour into 

 the lungs. Of this 20 c.c. it is no exaggerated estimate 

 to take one.-half, or 10 c.c, as absorbed by the pulmonary 

 blood, the other half being expelled in "the expired air. 

 If the subject breathes twenty times per minute 500 c.c. 

 at each inspiration, his blood absorbs 200 c.c. of chloro- 

 form vapour in one minute — i.e., one gram of fluid chloro- 

 form. He may, of course, absorb less than one gram 

 per minute ; but he may also absorb more. .Snow 

 estimated that 17 minims of chloroform in the blood 

 (i.e., about one gram) was sufficient to produce anaesthesia, 

 while double the amount was fatal. 



Grehant found that after death by chloroform the blood 

 contained half a gram of chloroform per litre of blood — 

 i.e., five litres of blood, which is the normal amount in 

 an average man, would contain two and a half grams. 

 Buckmaster and Gardner find from numerous experiments 

 results that may be summarised as follows : — 

 Ouantitv of chloroform (in grams) contained in 100 grams 

 of blood : 



Mn. "ean Max. 



Taken during deep anxsthesia 0-020 0-030 0040 



Taken after death by anaesthesia ... 0-040 0050 0-060 



1 Snow, "On Chloroform and other .'^naslhetics." 1S5S. 



2 Paul r.en. 3 Greh.-int. J F. Dubo's. 5 B.M.A. 



NO. 1972, VOL. 76] 



These results signify in five litres of blood between one 

 and two grams as the ana-sthetic amount, between two 

 and three grams as the lethal amount. 



Consider, then, what might happen if a patient were to 

 absorb chloroform at anything like the rate of one gram 

 per minute, and what might happen if by mischance he 

 should absorb two or three grams in a fraction of a 

 minute. This is a mischance thai can occur in the 

 ordinary method of inducing anaesthesia : a few deep gasps 

 by a struggling patient, a few moments' inattention on 

 the part of an administrator, and the blood almost at once 

 be fatally overloaded with chloroform. 



In the early days of chloroform ana'sthcsia it used to be 

 considered admissible to administer chloroform vapour of 

 4 and 5 per cent, strength in air ; but at that time the 

 means of estimating percentage were very imperfect, and 

 the figures quoted were little better than guesswork. 



The dictum of the Edinburgh school was " plenty of 

 chloroform with plenty of air by continuous administra- 

 tion." 



Some ten years ago, at a meeting of the Society of 

 Anaesthetists,' I pleaded for the continuous administration 

 of chloroform vapour at a strength (in air) of not below 

 I per cent, and not above 2 per cent., which amounted 

 to a translation into figures of the Edinburgh dictum, with 

 justification of the figures by quantitative observation. 

 Perhaps I may briefiy explain the method - by which the 

 percentages of chloroform and air are obtained : — 



A litre, or 1000 c.c, of chloroform vapour w-eighs 5-3.33 

 k litre, or 1000 c.c, of air weighs 1-288 



The litre weight difference is therefore 4-045 



The weight difference of i c.c. is approximately 4 milli- 

 grams. 



So that a 100 c.c. flask in which 1, 2, 3, &c., c.c. of air 

 are replaced by i, 2, 3, &c., c.c. of chloroform vapour is 

 4, 8, 12, &:c, milligrams heavier than the same flask 

 filled with air. 



So that added weights of 4, S, 12, &c., milligrams 

 indicate i, 2, 3, &c, per cent, of chloroform vapour 

 present. 



Thus, bv simply counterpoising a too c.c. flask (or, 

 preferably, a 250 c.c. bulb, so as to give weight increments 

 of 10, 20, 30,' &c., milligrams as indications of i, 2, 3, 

 &c., per cent.) filled with" air against a similar bulb filled 

 with chloroform mixture, the percentage of the mixture 

 is read directly by the number of centigrams required to 

 counterpoise. For- instance, a bulb full of mixture being, 

 say, 18 milligrams heavier than when it is full of air, 

 the chloroform vapour percentage is known to be 1-8 per 

 cent. 



Evidently, with a ready means of estimating percentage, 

 one is entitled to talk about the percentages that one 

 considers from experiment to be necessary and sufficient 

 and excessive. 



My argument up to this point comprises one or two 

 tacit assumptions that ought to be briefly dealt with, or, 

 at any rate, mentioned. 



In the first place, I have assumed that the great 

 majority of accidents by an;esthetics are caused by chloro- 

 form. 



This is accounted for by the fact that chloroform is 

 the most powerful, the most convenient, and the most 

 extensively used of all anaesthetic vapours. I hasten to 

 add that, in my opinion, this fact is an argument not so 

 much for the substitution of other less dangerous 

 anesthetics as for the more careful administration of 

 chloroform itself. 



In the second place, I have assumed that chloroform 

 is a remarkably uniform and certain reagent, producing 

 its physiological effects in strict conformity \vith the 

 quantity of vapour administered, and by no means irregular 

 in its action by reason of irregularities or impurities of 

 manufacture. Pure chloroform is more powerful than 

 impure chloroform. 



I do not dwell upon these two points now ; nevertheless 

 I should like to say that these are not gratuitous assum'p- 

 tions, but, more properly speaking, results of observation 



1 Waller. British Medical Journnl, April ly, 1898. 



2 Waller and Geets, il'id.. Tune =o, IJ03. 



