LIBRARY OK Till- University of California. GIFT OF Class /yift/r^lc^f^ >^^Ar*J^ -; ^^ QUININE IN CHOLERA BY ERSKINE B. FULLBRTON, A. M., M. D., Professor of Materia Medica and Therapeutics, Starling Medical College, Columbus, Ohio. COLUMBUS, OHIO: Press of Nitschke Brothers, 1893. The Points of the Argument. The strong points in the following papers are, in the writer's opinion, as follows: The test accidently made in 1873 in the case that I pre- scribed for but did not see; the more extensive test-ex- periment made by Dr. Schlomann in San Antonio, Texas, in 1866; the fresh vegetable and sauerkraut test in the Ten- nessee Penitentiary in 1873. The constant reference by the different authorities to the analogies between, or identity of, cholera and malarial disorders. Why this reiteration unless the success of the remedy in cholera strongly suggested or supported the theory of the other disease? The pointing out the fallacy of using the remedy hypo- dermically, and the after ability to show about when and where the departure was made, from the earlier method of administration by the mouth, to the unphilosophical intra- venous and hypodermic methods. The general trend of the treatment in the worst cases to a mortality of about 20 per cent, only, which led me to assert that the method of administration in the Stille list with its 63 per cent, of mortality must have been the hypodermic, and to ask, as well, for a revised translation of the Putelli article with its at-first-asserted death rate of over 46 per cent. The facts and figures brought to prove, that the disease treated in the penitentiary at Xashville, Tenn., in 1873, could have been nothing other or less, than malignant Asiatic Cholera, kept in check by the constant administration^ of quinine in sufficient doses. f .*4\Ni^*J* 219784 c*yiS.'^ The figures showing the im])ossible doses of other remedies necessary to e([ual in inliil)itory effect forty grains of (|ninine, and thereby })roving this remedy to be the most promising, in wiiat wiser men, simihirly circumstanced, have tiMiued ''the state of tlie argument." The iact tliat tlie proofs come, empiric end foremost, making the method of reasoning inductive and not synthetic and seductive merely. The further fact that it is no new and untried i-emedy, with hypothetical potentialities, to which attention is here directed, but one which, by reason of its control over one low foi-ni of organism, has rendered habitable the great interior valley of The Light Continent, and will be as neces- sary as gun])owder, in the conquest and civilization of *'The Dark." The articles are, with corrections, chiefly verbal, as they appeared in the i^ew York Medical Record. E. B. F. Columbus, O., May 17, 1898. [ From the Medical Record, October 1, 1892. ] QUININE IN CHOLERA, By ERSKINE B. FULLERTON, A. M., m. D., Professor of Materia Medica and Therapeutics, Starling nedical College, Columbus, Ohio. In the volume entitled "• The Cholera Epidemic of 1873 in the United States," under- the head of " Notes on Treatment,-' quinine is referred to as having been given in small doses, at uncertain intervals, by two writers, and by one in conjunction with atropine, amounts not stated. In Dr. Edward O. Shakespeare's " Report on Cholera in Europe and India " no reference is made to quinine in the chapter in which treatment is considered, but it was used in the cities of Teruel, Toledo, and Tembleque in Spain during 1884. The dose is not mentioned in any case, nor the method, except in one only,. where it was the hypo- dermic, with a strong inference that it was so used in the two other cities. The journals at the time gave the dose as fifteen grains, administered hypodermatically. When we recall two well-known facts — first, that the Koch germ is found inside the intestine and not in the blood, and secondly, that the direction of quinine is toward the kid- neys, but little, under ordinary circumstances, escaping with the faeces — a reason for failure when administered hypodermaticallj^ is apparent. In 188-1 Koch places quinine next to mercuric chloride in develop- ment-inhibiting (not disinfectant) power, the former acting in strength of 1 to 5,000, the latter in that of 1 to 100.000. In other words, one- half grain of the mercurial is the required equivalent for growth-inhi- bition of ten grains of quinine. When it is recollected that the lethal 6 dose of the one is about two grains, and that of the other about two ounces, the disparity for practical effects is apparent. If five grains of quinine can inhibit the development of the spirillum in three pints of rice-water discharge in situ, what ill effect can be apprehended from four or six times that amount ? All this, however, is " reasoning after the event " with the writer. In the epidemic of 1873 the use of quinine was early begun in cases coming under my care in this city. In over thirty cases of choleraic diarrhoea there was only one that proved refractory to the quinine treatment, developing into what under the old nomenclature would be called a mild case of cholera. Of the severer or typical form of the disease I had five cases, in all ol' which quinine was given in doses of seven and one-half grains in solution in the usual way, by means of a sufficient quantity of aromatic sulphuric acid; and this dose was repeated at intervals of an hour and a half or two hours until the symptoms were under control, then in smaller doses at longer intervals. Ice was allowed from the first in guarded quantities, and, so soon as the tendency to vomit was sufficiently controlled, ice-water. In some cases a small amount of morphine was given, in others not. In all cases there was decided improvement after the first dose, and a steady abatement of the symptoms as the treatment progressed. The patient in whom the disease was, jjerhaps, farthest advanced when treatment was commenced vomited but three times and purged but twice after the first dose was given. In this case, with the typical pulse, thirst, cramps in extremities, sunken countenance, and loss of voice, the vomiting was incessant, and the constant discharge from the bowels had penetrated the mattress and stood in a pool on the floor beneath. In one case in which I was consulted by the physician in attendance, quinine was exhibited to the extent of fourteen grains in pill form. The patient's symptoms, typical as described, were con- trolled for forty-eight hours, he returning to his place of business on the second day. At the end of the above mentioned period the symptoms returned and he died in the course of a few hours, no quinine having been administered during the relapse. AVhile aware of the danger in forming conclusions too radical on the success of treatment in so limited a number of cases, and also bearing in mind that epidemic diseases differ in tractability and severity during different seasons of tlieir prevalence, and at differing periods of the same epidemic, yet I have been unable to rid my mind of the impression, strongly made nineteen years ago, that the quinine treatment had much to do with the results above recorded. That the disease prevalent in Columbus, O., in 1873 was of no mild type is shown by the report of Dr. Halderman, where, out of one hundred and thirty-eight cases recorded, there were ninety deaths, a mortality of more than sixty-five per cent. Permit me strongly to urge upon the physicians now treating the disease in quarantine or hospital that they try the remedy. I would suggest that one drachm be dissolved in three ounces of water by means of a sufficient quantity of dilute or aromatic sulphuric acid, and that of this solution a tablespoonful be administered and at once repeated if vomiting occurs, and afterward at intervals of an hour and a half, until thirty grains have been taken, and thereafter pro re nata. If judged best, a small amount of morphine may be added, or a few drops of chlorodyne — their necessity I doubt. There are a few provisos: 1. The ten grain doses should be in solution, so that in case of vomiting some may be retained. 2. That the patient be not already moribund from toxaemia, or in pulseless collapse. While the discoveries of the last few years render the theory of Dr. Cunningham, that cholera is " malaria perniciosa," untenable, there is nothing as yet by which we may infer that the treatment may not be essentiallv the same. [ From the Medical Record, December 10, 1892. ] SECOND PAPER. A former communication,^ giving my own experience during the cholera epidemic of 1873, contained a comparison between quinine and mercuric chloride, as to amounts necessary to inhabit the growth of the cholera spirillum. Since then, in a ten minute discussion of the '' Treatment of Cholera," before the Medical Section of the Mississippi Valley Medical Association, the following more complete list with comparative amounts was given. The list of inhibitor}^ amounts is from that of Professor Koch, made public in 1884, with the exception of tannic acid, from Cantani, and salol, from Lowenthal, the estimate for the latter being based upon his lowest amount for sterilizing or (as ' Medical Record, October 1, 1892. it did not always sterilize) inhibiting the growth of the germ. One grain of quinine, which inhibits in strength of 1 to 5,000, is used as the standard of comparison, and results are given in round numbers, as inhibitory amounts doubtless were. Inhibitory List with Deductions. Alcohol, 10 to 100 Quinine, 1 grain = 1 fluid ounce. Alum, 1 to 100 " 1 " =50 grains. Camphor, 1 to 300 *' 1 " = 16s grains. Ac. carbolic, 1 to 400 " 1 " = 12i grains. Oil peppermint, 1 to 2,000 " 1 " =2hM. Sulph. copper, 1 to 2,500 " 1 " = 2 grains. Salol, 1 to 100 " 1 " =50 grains. Tannin, 1 to 200 " 1 " = 25 grains. Cor. sublimate, 1 to 100,000 " 1 " = ^ grain. Forty grains of quinine is not a very formidable amount to be given in the course of a day, or, for that matter, in a few hours, if occasion required, but the relative quantities of these other drugs seem very large ; 2^ quarts of whisky, brandy, gin, or rum ; 666| grains of camphor, 500 grains of carbolic acid, 100 minims of oil of peppermint, 80 grains of blue vitriol, 2,000 grains of salol, 1,000 grains of tannin, 2 grains of mercuric chloride, Calomel having little if any effect upon the germ, and opium being necessary to control peristalsis in the guinea-pig, before he can be made to take the disease, the logic of the situation seems to point plainly to quinine as the least harmful, and therefore the most efficient remedy, even in choleraic diarrhoea, or in moderately severe attacks of cholera, where the treatment may be carried through several days. How would it be in " foudroyant," " fulminant," or " explosive " cases, where if anything is to be done it must be done quickly, and enough of the remedy given in the cours'^ of two or three hours to arrest multi- plication of the germ throughout the whole intestinal tract? In full view of the modern theory that such cases may be the result of toxic absorption rather than the presence of the spirilla in overwhelming numbers 'in the intestines, it seems but reasonable tliat l)y inhibiting the growth of the germ one may at least limit tlie furtlier production of the toxines. Whatever other treatment may be used, in foudroy- ant arsenicism we would hardly be justified in withholding the proper antidotes for arsenical poisoning. Even in septicaemia quinine as yet holds the field against all comers. The latest estimate from Hamburg (September 8. 1892), places 9 the death-rate at loiiy lour i)er cent., and the probability is that when the full count is in, the loss will closely approximate the old one of about fiCty per cent. So far as heard from, the good results to above date seems attributable to hypodermoclysis. The word comes from Paris that Beta naphthol (hydro-naphthol) has failed. ^ Salol has failed, and the reason of its failure is apparent when we know that Lowen- thaFs 20 grammes (300 grains) daily, which according to his theory should set free in the duodenum the large amount of 120 grains of car- bolic acid, only equals, after all, so far as inhibitory effect is obtained, 6 grains, or, estimating the carbolic' acid alone, less than 10 grains of quinine, the 45 grains of Gonzales, of Salvador, about 1 grain, and the 120 grains daily of Nicholson, of Patna, India, less than 3 grains of quinine. Tannin entroclysis has failed in spite ot Dr. Shakespeare's expressed opinion that " with such an instrument not only the whole length of the colon can be filled with the desired fluid, but also not infrequently a quantity can be made to pass the ileo-ctecal valve into the small intestine." That is to say, a small amount of the remedy be placed just where it is most needed. Quinine failed by the hypoder- mic method of administration in 1873 and 1884. The germ being inside the intestine, and not in the circulation, and the affinity of the remedy for the kidneys, and not for the bowel, this method of using it would seem as irrational as the administration of sulphites or sulphur by the mouth in the treatment of sycosis, chloasma, or scabies. That by this method of using quinine the damaged kidneys might be impeded in their function, and if there be aught in the old uraemic theory of blood-poisoning in cholera, this undesired event, insured by the further retention of urea and uric acid to the extent of about forty per cent, where complete suppression of urine has not occurred, is easv to understand. To reach the seat ol" the disease the remedy must be given by the mouth, and the only noteworthy objection to this use of quinine is the old idea that quinine, under certain conditions, is very irritating to the stomach. In the disturbed stomach of remittant fever we do not always regard this symptom, and it was my own experience in 1873 that this remedy seemed a very good anti-emetic in cholera. In the whole history of that epidemic (Woodworth, McClellan, et al.) there is, if I mistake not, but once inention of its having been vomited, and 'If the above rumor were not correct we should know it by this time, as it was certainly most extensively tried in Paris last vear. 10 in that case it was given in conjunction with capsicum, not repeated, the patient put upon other treatment and dying thereafter. Has (piinino by tlio month given good results in cholera!' I think it has. Botkin, in 1871, in the Wiene?' Med. Presse, reports a loss of but IT.'T iier cent, under the use of quinine. Tie gave 5-grain doses three or four (sic) times daily, and when vomited resorted to hypodermic injections of 8 grains frequently during the day. If the latter dose, dissolved as it was, had been given by the mouth, and in case of vomiting thereafter had been repeated until about 30 grains had been retained, and continued in snuiller doses so long as symptoms seemed to require it, there might have been a better result even than the above very favorable showing. Owing to a persistent denial on the part of the authorities at New Orleans that cholera had been imported there in 1873, the profession in the Mississippi Valley (to which this invasion was limited) was left to make its own diagnosis as to the nature of the disease then prevail- ing. As late as September of that year, or seven months after the epidemic broke out in that city, the New Orleans Medical and Surgi- cal Journal discredited the importation of the disease, and the editor admits having considered it at first catarrhal in character. Of the eighty cases first reported, forty-six went on record as cholera morbus, " cholera Asiatica appearing infrequently." The idea of a cholera Mississippiensis was very prevalent during the early history of the epidemic in the lower valley, and throughout its entire history many physicians held to the belief of its malarial origin. This is especially noticeable in Tennessee and Kentucky. Quinine is frequently men- tioned in treatment, but too often it is the last remedy of the list, and in but few cases, comparatively, is the size of the dose, the method employed, or the frequency of its administration noted. Good results occasionally obtain after 5 grain doses by the mouth, and several recoveries after rectal injections of the drug in varying quantities. One writer states that the disease was very fatal unless the patient was seen early and large doses of quinine given, and two instances are recorded where the patient recovered alter the large amounts of half an ounce in the one case and two-thirds ounce in the other, had been taken. On such data, however, it is impossible to arrive at any satis- factory conclusion other than that, generally, the results seem favorable. There is one exception to this rule, and the treatment and its 11 results are so very remarkable as to be nearly unique in the history of medicine, and on ^-o large a scale as almost to force conviction. As recorded in the volume entitled " The cholera Epidemic of 1873 in the United States," the facts are as follows : About May 1, 1873, the authorities in control of the Tennessee penitentiary at Nashville, Tenn., received notice that a malignant dis- ease had broken out among two camps of convicts at work along the line of the Memphis & Paducah Railroad. As to how fatal it was there are several conflicting statements. Fortunately we have, on page 137 of the above-mentioned volume, the report of the chief engineer of the road, Mr. J. L. Meigs, which gives the whole number sick of the disease from May 1st to 13th as forty, and the number of deaths twenty-four, a fatality of sixty per cent. On the 12th of that month convicts to the number of seventy-five were sent back to the penitentiary at Nashville, purging and vomiting. On arrival about one-half only of this number could be accommodated at the hospital, the remainder being shut up in cells, usually two in a cell having a capacity of two hundred and fifty cubic feet of air, ventilation being through a grating, fourteen inches square, in the cell door, with the bucket that received the choleraic discharges inside the cell. The diagnosis " scorbuto-malaria " was made by the physician of the penitentiary, and the sick put upon a diet of fresh vegetables and saurkraut, with " tincture of iron and quinine freely given^ chlorate of potash being used as an adjuvant." The day after the arrival one man died, this man on reaching the penitentiary " being in so much better condition than the others " that he was not admitted to the hospital, but sent to his cell. A letter recently received from Dr. George P. Henry, the physician, states that this patient had no medi- cal treatment whatever. " The remainder recovered rapidly, and in a few weeks most of them were at work.'- In the above-mentioned letter Dr. Henry further states that to these seventy-four cases " I gave quinine by the mouth altogether." " freely and at short intervals at first," and that '' the cases were usually under control in an hour or two after the administration of perhaps 20 or 30 grains of quinine," " that finding its potency for good I kept it up," using it later on "both by the mouth and hypodermically." Dr. W. M. AV right, at that time Superintendent of the penitentiary, in a letter recently received, states : " I think that 20 grains of quinine were given in about four hours." From May 12th to June 8th there was an average of fifty-seven 12 oases daily under treat iiicnt in ho^pilnl and in iclU. Al this last date there was an "explosion'' of the disease in the city of Nashville (brought there by these same convicts), and '"the (act was recognized that cholera was epidemic within the penitentiary walls." TJio dietary was changed in conformity to the corrected diairnosis. and during that day and the night following there were three deaths of prisoners from the disease. On June 9, 1873, Dr. Thomas Menees, a prominent practitioner and teacher of medicine in the city of Nashville, was called in counsel. and the treatment thereafter was as follows: Calomel and opium in small doses frequently repeated, "quinine freely given either by the mouth or hypodermically." In a meeting of the physicians of Nash- ville, held December 16, 1874 (1873 0, Dr. Henry further states, "after June 8th we treated the patfents with quinine, calomel, and opium." "I called it malaria." Dr. Menees. at the same meeting, said, "we also used quinine freely,"' and he ])lnces the whole numl)er treated at between four and five hundred. *" prisoners and attaches." In the letter from Dr. Henry above referred to, he places the numiier severe enough to be called cholera at three hundred and fifty, the rest choleraic diarrhoea. Dr. Menees states that '* from the 9th day of June to the 12th day of July there were twelve deaths. There were some that had chronic diseases, and when they were attacked they would die.'' It will be seen l)y the abov(> that there were fifteen deaths after the idea that the disease was malaria was given up and the proper diagnosis of cholera made, but only one death prior to this. There are three of these cases in which it is very doubtful that they had any quinine, or if so. whether it was given in sufficient doses in the light of modern discoveries to inhil)it the growth of the germ. Dr. Henry writes he cannot reineml)er whether the three dying on June S had quinine or not. It will be recalled that on that date the diagnosis of cholera was made. Count ing these, however, and allowing nothing for those al'-eady enfeebled by "chronic diseases,'' and taking the lowest figure (350) as the num- ber of cholera patients, and the result is a death rate of less than \^ per cent, finder similar circumstrrnrefi, onh/ thai the hnspital arrnm- modations were sufficient for alU the dietary arranged ^'iih reference 1o cholera and not to scxirvy, and only a few of the diarrhhuric ether, alcohol, and peppermint oil. '' Should symptoms become worse, how- ever, and vomiting, cramps, and abdominal pains come on with the well known cholera excreta, then one should give, every half-hour, four to six grains of quinine, with warm bath." He uses champagne and ice for vomiting, and says, '■ I verv seldom use narcotics, especially 23 in large does. . . . Often, nay, almost always, did I see distinct collapse come on in those sick to whom the Chinese doctors gave large doses of narcotics. . . . Bleeding, which was used in the beginning of the epidemic of 1858 by the Japanese physicians, usually caused death. As soon as the crisis has appeared one should continue for some time the use of the quinine, as otherwise there is danger of exacerbations, during which the sick may yet die. Later, the dose may be decreased. . . . There need be no fear of quinine intoxi- cation. ... I saw this intoxication but three times, and warm baths, cold affusions to head, port wine and beef-tea soon obviated these symptoms." The writer shows his theory-bias by the remark : " The use of quinine in cholera or similar malarial epidemics is to be recommended, especially in the tropics. . . . I do not wish to say that I consider it as a certainty that pernicious fever and cholera are identical.'" " The cholera mixture I prescribed in Nagasaki has the following formula : T?, Sulphate of quinine 1 drachm Dilute muriatic acid 1 drachm. Alcoholic sulphuric ether IJ diachm. Eleo-sacch. menth. \np 2 drachms. Pure water 8 ounces. In mild cases one tablespoonful every half-hour ; on improvement, every hour ; in severe cases one tablespoonful every quarter hour ; on improvement every half-hour, and then in decreasing doses. After a short use of the above mixture there is usually improvement, at least if it is used in time. . . . The number — 2,467 — here given, pertains only to those cases treated by me personally — all severe and well developed cases of cholera — not cholerine. Of these one-sixteenth were treated in hospital, fifteen-sixteenths outside in the city. The Japanese physicians who followed my treatment obtained just as favorable results." The hypothesis is often used as a method of arriving at accurate results in the exact sciences Let us suppose that instead of one physician to 60,000 people, there had been the usual ratio obtaining in the United States, of one to five hundred population ; that instead of a vegetable and fruit-eating population (the Buddhist priests in Japan have only in the last few years begun to frequent the butcher stalls) there had been a better fed people of a stronger vitality to deal with ; that instead of seeing these cases only in the severest stage of cholera, 24 llu'v liiul hec'ii seen iluriiiir the cnrlier slnjiC's of choleraic diarrlKra. ov so-called cholerine, what an enormous reduction in tlie niortalily niiirht have been secured by this treatment can best be.judiied by the results in the 'i'ennessee Penitentiary in 1878, of which Jiiore anon. The more exact mortality of Dr. \'an Meerdervoort's cases was 20.22 l>er cent. W. (). Shakespeare says, " In Ja]»an in 1854, there occurred 154,373 cases, with 101,(>9r) deaths, a mortality of (Ul.S. slK)win^- the ordinary severity of the disease in Japan."* Di-. A. Schloniann' says: '' In the cholera epidemic of the Mis- sissippi Valley and the Gulf States, summer and fall of 18Hf), several American physicians obtained surprisingly good results from the sulphate of quinine. Such a coincidence might seem strange, but is explained, however, by the fact that everywhere in these States the appearence of cholera came during the time for intermittent fevers. This would tend to experimentation with quinine salts, which are the staple drugs of the Southern pharmacist. . . . Our cholera loas the real cholera of the Ganges Delta axd )\ot a doubtful hybrid form of intermittent. . . . The tbllowing observations were made during the epidemic in San Antonio de Bexar, a town in Western Texas, having a population of l(),0