May 29, 1 9 19] 



NATURE 



255 



normal fluidity of the blood, and found them, as I had 

 suspected, to be much greater in severe cases than 

 had formerly been given when isotonicsolutions were 

 in use. The haemocrite, however, is too much of a 

 laboratory instrument to be generally available, so a 

 simple bedside method was needed. I therefore made 

 use of Lloyd-Jones's method of estimating the specific 

 gravitv of the blood by means of a series of solutions 

 of glycerine in water in small labelled bottles into 

 which small drops of blood are gently blown from 

 ;i capillarv tube, and that in which one just floats 

 is noted, which gives the required estimation. When- 

 ever the pulse tends again to fail, the test is repeated 

 as a guide to further treatment, and in several ex- 

 tremely severe cholera patients more than thirty pints 

 of fluid have thus been injected in the course of 

 several days with ultimate success in saving the lives 

 of tlie patients. 



Permanganates and Oiher Drugs in the Treatment of 

 Cholera. 



The success of the hypertonic saline injections in 

 enabling the collapse stage of cholera largely to be 

 overcome opened the way to a trial of drug treatment 

 such as had never before been possible ; for it is clear 

 that, unless the circulation can be restored and main- 

 tained, drugs given by the mouth will not even be 

 absorbed, and can have no chance of exerting their 

 beneficial action. Great care is required to make such 

 tests trustworthv on account of the numerous sources 

 of fallacv in estimating the effects of a given treat- 

 ment. The best plan is to use a new drug in every 

 other case in addition to the routine treatment, the 

 remaining half of the cases then serving as a control. 

 To take an example of this method of investigation, 

 the late Sir Lauder Brunton some years ago advo- 

 cated on physiological grounds the use of atropine in 

 cholera, but was only able to try it in two mild cases 

 with inconclusive results. I therefore gave the drug 

 hvpodermically in addition to the routine treatment 

 in everv other case of cholera in my wards for a whole 

 vear with the result that the mortality was much 

 lower in the atropine series, while a careful com- 

 parison of the tv.o sets of cases as regards their 

 severit\- showed them to be strictly comparable. I 

 have, therefore, added atropine to my system of treat- 

 ment with, I am sure, beneficial results. In a similar 

 manner emetine was found to be useless in cholera. 



•Another point I wish to emphasise is the import- 

 ance of carefullv studying one's failures rather than 

 being elated with anv success, as the further progress 

 T have still to relate is mainly due to my adopting 

 that practice. For the last ten years I have tabulated 

 with the aid of shorthand — of the value of which in 

 mv work I cannot speak too highly — all the more 

 important points of mv cholera cases, now amounting 

 to a little more than two thousand, and have closely 

 studied the records of all fatal cases to ascertain the 

 reasons for the failures with the view of finding means 

 of lessening them. The foHowin<* examples will illus- 

 trate some of the results thus obtained. 



After an experience of a vear and a half of the 

 hypertonic treatment T realised that something more 

 was requirpd if the mortality was to be reduced still 

 further. The failures appeared to me to be due 

 largely to a recurrence of the collaose on account of 

 absorption of the ttjxins produced by the cholera 

 bacillus in the intestinal canal with the restoration of 

 the circulation after the saline injections. Now the 

 toxins are contained in the bodies of the innumerable 

 bacilli, and set free when thev break up. as thev 

 do in enormous numbers, for it has been shown that 

 no fewer than 00 per cent, of comma bacilli die in 

 culture-tubes within fortv-eight hours. The u.se of 

 intestinal antiseptics ma\ verv possibly add to the 

 NO. 2587, VOL. TO.;] 



toxin absorption by killing the bacilli, which is, I 

 believe, one of the reasons for their failure, as already 

 stated. I therefore sought for some method of 

 destroying the toxins themselves while still unabsorbed 

 in the bowel ; and, bearing in mind that they are 

 largely albumoses and other unstable albuminous pro- 

 ducts of the metabolism of the organisms, and that 

 such substances are readily destroyed or rendered inert 

 bv oxidisation, I experimented with various oxidising 

 agents, and particularly with permanganates, which 

 are well known to destroy rapidly in vitro the 

 albumoses of snake venoms — a point at which I had 

 previously worked. I was thus able to demonstrate 

 that several times a lethal dose of dead comma bacilli 

 containing the toxins could be neutralised by a small 

 quantity of permanganates. A trial of large doses of 

 permanganate of potash in pill form by the mouth, 

 .as much as one hundred grains sometimes being given 

 in the course of several days, in addition to the hyper- 

 tonic treatment, reduced' the mortality of cholera 

 during a year's use from 326 to 23-3 per cent., and it 

 has now been used for more than nine years in my 

 wards with increasingly favourable results. Perman- 

 ganate pills have also been used in cholera epidemics 

 in both the Bombay Presidency and the Central Pro- 

 vinces, in villages under conditions in which the saline 

 treatment was not practicable, and favourable results 

 have been reported, although, of course, it cannot by 

 itself save the most severe cases with extreme collapse. 



Alkalis ni the Prevention of Fatal Renal 

 Complications. 



There still remained one very important line of 

 investigation, which has recently led to a further sub- 

 stantial reduction of the death-rate of cholera by 

 enabling the common and most deadly suppression of 

 the renal function largely to be averted. I know of 

 nothing more disheartening than, after successfully 

 maintaining the circulation by hypertonic salines 

 through a life-and-death struggle for several days and 

 nights, to be unable to get the kidneys to resume 

 their functions, with ultimate loss of the patient. As 

 the losses from collapse were steadily reduced by the 

 various measures I have related, the death-rat<" from 

 kidney failure continued much the same, and now 

 becarne the most important remaining cause of loss 

 of life, and. it was apparent that some factor remained 

 which was not clearly understood. 



Light was first thrown on this problem by an 

 American physician. Dr. .Sellards, working in the 

 Philippines, who suspected a diminution in the 

 alkalinity of the blood, or acidosis as it is generally 

 termed, because he found that large doses of alkalis 

 by the mouth failed to* make the urine alkaline as it 

 would do in health. He therefore added sodium bicar- 

 bonate to the saline solution used in cholera for intra- 

 venous injections, and obtained a marked reduction 

 in the death-rate from renal failure. In 191 1 Maior 

 Megaw, when acting for me in Calcutta, read Sel- 

 lards's work, and tried alkaline solutions intravenously 

 in cases of cholera with suppression of urine, but with 

 disappointing results, the measure being apparently 

 too late once this complication had become established. 

 Earlv in igi2 I therefore commenced an investigation 

 of the changes in the alkalinity of (he blood in 

 cholera, which Sellards had not then done, and finding 

 an extreme decree of reduced alkalinity in all cases 

 with fatal kidney trouble, with the help of Cant. 

 .Shorten, and later of Rai Satish Ch. Banerjee 

 Bahadur, of tlie Physiological Department, I made a 

 lonj? series of such estimations in cholera cases, with 

 the result of demonstrating^ that a verv marked de£*ree 

 of diminution of the alkalinity of the blood occurred 

 in all cholera cases, while once it reached the extreme 

 degree of N'loo from a normal of about N/z-; fata' 



