WITHERING ON DIGITALIS, 1785 By W. T. DAWSON, M.A. (OXON.) AND JOHN CHAPMAN, M.D.

GALVESTON, TEXAS OSAWATOMIE, KANSAS

AN excellent account of the sickness, vomiting, purging, giddiness, life and work of William confused vision, objects appearing green Withering has been given by or yellow; increased secretion of urine, Cushny,1 who said of one with frequent motions to part with it, of his paragraphs (1), “ Withering sums and sometimes inability to retain it; slow up in this paragraph the main prin­ pulse, even as slow as 35 in a minute, cold sweats, convulsions, syncope, death. ciples of digitalis treatment.” I am doubtful whether it does not some­ Withering s ‘‘On ’ great monograph times excite a copious flow of saliva the Foxglove,”2 published in 1785, [citing 3 cases, of the last of which] the should be available to every student, superabundant flow of urine continued but this classic work is a rare and for the first three days after his last costly curiosity among medical books, course; but since, the flow of saliva has as no English reprint seems to have been nearly equal to that of urine. been made. The intention of the When given in a less violent manner, present writers is simply to set forth it produces most of these effects in a lower interesting parts of Withering’s ac­ degree; and it is curious to observe that count of experiences with digitalis, in the sickness, with a certain dose of the his own words. medicine, does not take place for many hours after its exhibition has been dis­ It is better the world should derive continued; that the flow of urine will some instruction, however imperfect, often precede, sometimes accompany, from my experience, than that the lives frequently follow the sickness at the of men should be hazarded by its un­ distance of some days, and not unfre- guarded exhibition, or that a medicine quently be checked by it. The sickness of so much efficacy should be con­ thus excited, is extremely different from demned and rejected as dangerous and that occasioned by any other medicine; unmanageable. . . . it is peculiarly distressing to the patient; Time will fix the real value upon this it ceases, it recurs again as violent as discovery, and determine whether I have before; and thus it will continue to recur imposed upon myself and others, or con­ for three or four days, at distant and more tributed to the benefit of science or man­ distant intervals. kind. . . . These sufferings of the patient are In the year 1775, my opinion was asked generally rewarded by a return of appe­ concerning a family receipt for the cure tite, much greater than what existed of the dropsy. . . . This medicine was before the taking of the medicine. composed of twenty or more different But these sufferings are not at all herbs; but it was not difficult for one necessary; they are the effects of our conversant in these subjects, to perceive inexperience, and would in similar circum­ that the active herb could be no other stances, more or less attend the exhibition than the Foxglove. of almost every active and powerful medicine we use. EFFECTS, RULES, AND CAUTIONS Perhaps the reader will better under­ The Foxglove when given in very large stand how it ought to be given, from the and quickly repeated doses, occasions following detail of my own improve­ ment, than from precepts peremptorily I mean, they should drink whatever they delivered, and their source veiled in prefer, and in as great quantity as their obscurity. appetite for drink demands. This direc­ At first I thought it necessary to bring tion is the more necessary, as they are on and continue tbe sickness, in order to very generally prepossessed with an idea ensure tbe diuretic effects. of drying up a dropsy, by abstinence I soon learnt that the nausea being from liquids, and fear to add to the once excited, it was unnecessary to repeat disease, by indulging their inclination to the medicine, as it was certain to recur drink. frequently, at intervals more or less In cases of ascites and anasarca; when distant. the patients are weak, and the evacuation Therefore my patients were ordered to of the water rapid; the use of a proper persist until the nausea came on and then bandage is indispensably necessary to to stop. But it soon appeared that the their safety. diuretic effects would often take place If the water should not be wholly first, and sometimes be checked when the evacuated, it is best to allow an interval sickness or a purging supervened. of several days before the medicine be The direction was therefore enlarged repeated, that food and tonics may be thus—Continue the medicine until tbe administered; but truth compels me to urine flows, or sickness or purging takes say, that the usual tonic medicines have place. in these cases very often deceived my I found myself safe under this regula­ expectations. tion for two or three years; but at length From some cases which have occurred cases occurred in which the pulse would in the course of the present year, I am be retarded to an alarming degree, with­ disposed to believe that the Digitalis may out any other preceding effect. be given in small doses, viz., two or three The directions therefore required an grains a day, so as gradually to remove a additional attention to the state of the dropsy, without any other than mild pulse, and it was moreover of consequence diuretic effects, and without any inter­ not to repeat the doses too quickly, but ruption to its use until the cure be to allow sufficient time for the effects of compleated. each to take place, as it was found very If inadvertently the doses of the Fox­ possible to pour in an injurious quantity glove should be prescribed too largely, of the medicine, before any of the signals exhibited too rapidly, or urged to too for forbearance appeared. great length; the knowledge of a remedy *Let tbe medicine therefore be given in to counteract its effects would be a the doses and at the intervals mentioned desirable thing. Such a remedy may above:—Let it be continued until it acts perhaps in time be discovered. . . . either on the kidneys, the stomach, the pulse, or the bowels; let it be stopped upon Withering recognized the action of the first appearance of any one of these digitalis upon the heart in his state­ effects, and I will maintain that the ment, “that it has a power over the patient will not suffer from its exhibition, motion of the heart, to a degree yet nor the practitioner be disappointed in unobserved in any other medicine, any reasonable expectation. [Only the and that this power may be converted continuance with small maintenance dos­ age is omitted.] to salutary ends,” and in the remark If it purges, it seldom succeeds well. already quoted that the pulse might The patients should be enjoined to be “retarded to an alarming degree, drink very freely during its operation. without any other preceding effect.” Withering described a type of con­ had not been in bed for many weeks. His gestive heart failure responding well countenance was sunk and pale; his lips to digitalis: livid; his belly, thighs, and legs very greatly swollen; hands and feet cold, the If the pulse be feeble or intermitting, nails almost black, pulse 160 tremulous the countenance pale, the lips livid, the beats in a minute, but the pulsation in skin cold, the swollen belly soft and the carolid [sic] arteries was such as to fluctuating, or the anasarcous limbs be visible to the eye, and to shake his readily pitting under the pressure of the head so that he could not hold it still. finger, we may expect the diuretic effects His thirst was very great, his urine small to follow in a kindly manner. in quantity, and he was disposed to purge. I immediately ordered a spoonful His case reports are short and to of the infusum Digitalis every six hours, the point. with a small quantity of laudanum, to prevent its running off by stool, and decoction of leontodon taraxacum (dande­ 1775. Case 1. December 8th. A man lion) to allay his thirst. The next day he about fifty years of age, who had formerly began to make water freely, and could been a builder, but was now much allow of being put into bed, but was reduced in his circumstances, complained raised high with pillows. Omit the in­ to me of an asthma which first attacked fusion. That night he parted with six him about the latter end of autumn. quarts of water, and the next night could His breath was very short, his counte­ lie down and slept comfortably. July 21st, nance was sunken, his belly large; and, he took a mild mercurial bolus. On the upon examination, a fluctuation in it was 25th, the diuretic effects of the digitalis very perceptible. His urine for some time having nearly ceased, he was ordered to past had been small in quantity. I take three grains of the pulv. Digital, directed a decoction of Fol. Digital, night and morning, for five days, and a recent, which made him very sick, the draught with half an ounce of vin. sickness recurring at intervals for several chalyb. twice a day. August 15th. He days, during which time he made a large took a purge of calomel and jallap, and quantity of water. His breath gradually some swelling still remaining in his legs, drew easier, his belly subsided and in the Digitalis infusion was repeated. The about ten days he began to eat with a water having been thus entirely evacu­ keen appetite. He afterwards took steel ated, he was ordered saline draughts and bitters. with acetum scilliticum (vinegar of squill) 1784. Case cxxxii. July 16th. Mr. and pills of salt of steel and extract of B------, of W------, ALt. 31. After a gentian. About a month after this, he tertian ague of 12 months continuation, returned home perfectly well. suffered great indisposition for 10 months more. He chiefly complained of great Withering also had to deal with the straitness and pain in the hypochondriac self-prescribing patient. Case cvi region, very short breath, swelled legs, (1782) is that of a disobedient patient, want of appetite. He had been under the who continued to take digitalis against care of some very sensible practitioners, directions; he suffered “many days” but his complaints increased, and he determined to come to Birmingham. I from “reaching,” green vision, and found him supported upright in his chair, pulse rate of “down to forty,” with by pillows, every attempt to lean back great weakness. or stoop forward giving him the sensation His friend, Dr. Stokes of Stour­ of instantaneous suffocation. He said he bridge, described death from overdose of digitalis at the Edinburgh Infirmary we have spirituous, vinous and acetous in 1780: tinctures; extracts hard and soft, syrups with sugar or honey, &c but the more we In one case in which it was given multiply the forms of any medicine, the properly at first, the urine began to flow longer we shall be in ascertaining its real freely on the second day. On the third the dose. swellings began to subside. The dose was then increased more than quadruple in Withering left some suggestions the twenty-four hours. On the fifth day, as to dosage. “I give to adults, from sickness came on, and much purging, but one to three grains of this powder the urine still increased though the pulse twice a day.” “About thirty grains sunk to 50. On the 7th day, a quadruple dose of the infusion was ordered to be of the powder . . . may generally taken every third hour, so as to bring on be taken before the nausea com­ nausea again. The pulse fell to forty-four, mences.” This is close to the average and at length to thirty-five in a minute. massive dose figure sometimes used The patient gradually sunk and died on today. Withering himself also some­ the sixteenth day; but previous to her times carried out rapid digitalization, death, for two or three days, her pulse as in the following case. rose to near one hundred. Case xliii, 1780. I then directed Pulv. It is not easy for most men to Fol. Digital, two grains every four hours. learn how to give digitalis properly. After taking eighteen grains, the urine Withering commented that a remedy began to increase. The medicine was then “will ever be subject to the whims, stopped. The discharge of urine continued the inaccuracies and the blunders of to increase. . . . mankind,” and With regard to redigitalization . . . in the year 1783, it [i.e., digitalis] Withering says: appeared in the new edition of the Edinburgh Pharmacopoeia. But from I have often been obliged to evacuate which, I am satisfied, it will be again very the water repeatedly in the same patient, soon rejected, if it should continue to by repeating the decoction. ... In these be exhibited in the unrestrained manner cases the decoction becomes at length so in which it has heretofore been used at very disagreeable, that a much smaller Edinburgh, and in the enormous doses quantity will produce the effect. in which it is now directed in London. Withering attempted to secure a References standard preparation by taking only 1. Cushny, A. R. William Withering, m.d., leaves gathered when the plant was in f.r.s. Proc. Roy. Soc. Med., 8 (Sect, on flower, and drying them carefully. Hist, of Med.) 185,1915. The paragraph referred to by Cushny is that indicated At he a later an first used decoction, by an asterisk on page 32. infusion, and in the end powdered 2. Withering, William, m.d., Physician to leaf or infusion. He was annoyed by the General Hospital at Birmingham. the needless multiplicity of drug An Account of the Foxglove and Some preparations, for he says: of Its Medical Uses: with Practical Remarks on Dropsy, and Other Dis­ The ingenuity of man has ever been eases. Birmingham: Printed by M. fond of exerting itself to vary the forms Swinney; for G. G. J. and J. Robinson, and combinations of medicines. Hence Paternoster-Row, London, m, dcc.lxxxv.