Part 9

6. Notwithstanding the prompt removal of the pain and reduction of the fever by the salicyl compounds, the average duration of acute articular rheumatism is not very considerably lessened by those remedies. Thus, of Hood's 350 cases treated by salicylates the average duration of the illness was 35.95 days as against 38.75 under other methods. The average time spent in bed by Warner's 342 cases was 19.5 days under the salicylates, and by 352 patients under other remedies 23.5 days. Both estimates show a curtailment of the duration of the disease by the new treatment of three to four days only; which is not a very material improvement.

{56} 7. Nor do the salicylates materially alter the time spent in hospital by rheumatic patients; some evidence indicates that they actually prolong that period. The following are the average residences in hospital under the salicylates, according to several recent authors, and they are remarkably uniform with two exceptions: Coupland, 36 days; Warner, 34.9; Hall, 34; Southey, 32.5; Broadbent, 31.2; Powell, 31; Finlay and Lucas, 29.7; Owen, 23; Brown, 21.9; or a general average of 30.4 days for the salicyl remedies. Under full alkaline treatment: Owen, 26 days; Dickinson, 25; Fuller, 22.2; Blakes, 24; or a general average of 24.3 days for full alkaline treatment. And if to these we add Finlay and Lucas's results, 27.7 days, under but two to three drachms of alkaline salts in the twenty-four hours--a quantity only the fourth of that given under the full alkaline method--the general average residence in hospital under alkaline treatment was but 25.4 days; that is, five less than under the salicylate.

These several estimates of the time spent in hospital under the salicylates, with the exception of Owen's and Brown's, correspond closely with that of the time spent by Gull's and Sutton's patients under mint-water--32.8 days--although the general average of them falls short of the latter by 2.4 days.

The following table (iii.) of Hood's shows that under the salicylate method 45.7 per cent. remained in hospital beyond forty days, and 39 per cent. under other methods, and that about 50 per cent. more were discharged within twenty days under the other methods than under the salicylate:

350 cases treated with salicylates: Days. Under 10. Under 20. Under 30. Under 40. Ill longer. 3 = 0.84%. 31 = 8.88%. 76 = 21.7%. 84 = 24%. 160 = 45.7%.

850 without salicylates: Days. Under 10. Under 20. Under 30. Under 40. Ill longer. 12 = 1.4%. 105 = 12.35%. 175 = 20.1%. 182 = 21.4%. 331 = 39%.

These statistics favor Greenhow's opinion that patients treated with salicylate of sodium regain their strength slowly, and are long in becoming able to resume their ordinary occupations. Some allowance, however, must be made for the precautions against relapse under salicylates observed in hospitals since the great tendency thereto has been recognized.

8. Certain unpleasant or toxic effects are produced by salicylic acid and salicylate of sodium; such are nausea, vomiting, abdominal pain, frontal headache, tinnitus, incomplete deafness, vertigo, tremor, quickened respiration, very rarely amblyopia and even temporary amaurosis, and not unfrequently delirium. A feeling of prostration and general misery is not uncommon. These phenomena of salicylism are in great measure proportionate to the dose employed, but they have followed moderate {57} doses, owing sometimes to idiosyncrasy, and perhaps frequently to retarded elimination consequent upon previous disease of the kidneys or disturbance of their function by the salicylic acid or its salt. Those agents are usually completely excreted in forty-eight hours, but in one of Powell's cases elimination was not completed before the fifth day, and not before the eighth in Byanow's case. Possibly uræmia may in some cases cause the delirium. The delirium, which may be violent or not, is often preceded by dryness of the tongue, restlessness, and rapid breathing. Impurities in the acid may account for the inconstancy with which delirium has been noticed by different observers. While but 2 instances in 82 cases were met with by Coupland, 3 out of 90 cases by Broadbent, and 3 out of 109 by Brown, Charles Barrows encountered 8 instances in 28 cases. In one of these a boy of eleven became delirious in eighteen hours, having taken 10 grs. of salicylate of sodium every three hours. In another instance the drug had been in full use for five days before the delirium manifested itself. These phenomena of salicylism rapidly disappear when the medicine is stopped, and delirium has not always recurred on its resumption. They are less frequent in children, in whom elimination by the kidneys takes place very rapidly and a marked tolerance of salicyl compounds exists. Occasionally more serious effects appear to be produced by the salicylates, owing to their direct action on the heart, impairing its power, as evidenced by feeble impulse and sounds, increased frequency of the pulse, and diminution of the arterial pressure. But, notwithstanding the very large number of cases of acute rheumatism that have been treated by the salicyl compounds, very few clear instances of their toxic action on the heart have been recorded, and even in some of these there were other conditions present that may have played some part, perhaps a chief part, in the production of cardiac failure. In Greenhow's case the autopsy revealed a dilated fatty heart and slightly granular kidneys, and the cardiac failure coincided with a fall of temperature to 97° F. Goodhardt's patient died in nine hours after beginning the salicylic acid, of which she took but one drachm, in divided doses, every three hours. The pulse rose rapidly to 160; she was restless and moaning, but died quietly and suddenly. Recent pericarditis, with one or two points of fatty degeneration of the heart's substance, and sound kidneys were found. The reporter of the case inclines to the opinion that the acid produced sudden collapse and cardiac failure, while Bristowe referred them to the rheumatic poison itself. I have not been able to refer to Hoppe Seyler's paper, in which he relates that having given 5 grammes of salicylic acid to a child of seven and a half years affected with articular rheumatism, shortly afterward there occurred deafness, agitation, profuse sweating, dyspnoea, and finally fatal collapse. The condition of the heart and kidneys before and after death is not given. Weber {58} published an instance in which 15-gr. doses of salicin given to a woman of twenty-seven produced in thirty-four hours a rapid fall of temperature from 103° to 96° F., accompanied by delirium and serious but not fatal collapse. It is well to remember that a similar failure of cardiac power is occasionally observed in other fevers when rapid defervescence occurs, although the salicyl compounds have not been taken; and it is certainly necessary to give these remedies cautiously, and often to administer alcohol with them, when the heart's action is at all enfeebled by protracted pyrexia and pain, or by disease (inflammatory or degenerative) of its substance or envelope. Indeed, if severe cardiac inflammation obtain in rheumatism, the remedies are powerless and perhaps unsafe. The sudden reduction of the temperature when much exhaustion obtains, even in the hyperpyrexia of rheumatic and other fevers, whether by salicylic acid or quinia or the cold bath, may be attended with fatal collapse of the heart.

Instead of the frequent weak pulse above mentioned, I have many times found salicylate of sodium render the pulse very slow, labored, and compressible in typhoid fever, and generally at the same time the temperature has been considerably reduced below what it had been.

A temporary albuminuria is not infrequent; excluding mere traces, it obtained in 52 per cent. of cases treated by the salicylates alone or in conjunction with full doses of alkali, and in but 25 per cent. of those in which full doses of alkali, with or without quinia, were employed.

Very rarely hæmaturia and even nephritis have occurred. The active principle is chiefly eliminated by the kidneys, which may account for a local irritating influence upon those organs.

Salicine is much preferred by Maclagan to salicylic acid and to salicylate of sodium, on the grounds that it is a bitter tonic and produces less debility and more rapid convalescence than those agents, and that it never produces delirium nor depresses the heart's action. Ringer and Charteris state that they have never seen salicine, even in large doses, cause delirium; and Prof. Gairdner has not found it produce any unfavorable symptoms. On the other hand, Greenhow found that marked depression of the heart's power ensued in 4 out of 10 cases whilst the patients were taking salicine, and entirely subsided after it was discontinued. Further careful and extended observation is needed before the relative value of salicine and salicylate of sodium can be reliably stated. It is probable that the salt is more active and prompt than the bitter principle; and this, with the greater cheapness of the former, may perhaps account for the more general employment in hospitals of the salicylate than of salicine. The latter, moreover, is often tolerated when the former is not.

As regards the doses of these agents required in acute rheumatic arthritis, practitioners are not agreed; Maclagan, Stricker, Fagge, Broadbent, Ringer, Flint, Sée, recommend large doses at short intervals at the outset, with the view of getting the patient rapidly under the influence of the drug. Maclagan gives salicine scruple i-ij at first hourly, then every two hours {59} as the acute symptoms begin to decline; after the second day he allows 20 to 30 grs. every four hours for two or three days; "and for a week or ten days more that quantity should be taken three times a day." Stricker, Fagge, Broadbent, and Sée recommend about 20 to 30 grs. of salicylate of sodium every hour or two for six doses (= drachm ij-iij in the day), and Ringer would employ 10 grs. hourly, and if in twenty-four hours this dose has not either modified the disease or produced its characteristic symptoms, he would increase it to 15 and then to 20 grains hourly. On the other hand, Owen's results show practically no difference in the duration of pain and pyrexia and in the average duration of illness from the commencement, whether drachm iij or drachm ij or drachm iss were given every twenty-four hours; and C. G. Young found that 10 to 15 grs. every one, two, or three hours are sufficient.

Indeed, exceptionally good and exceptionally indifferent results are reported under similar doses. No such good results are reported as those of the Boston City Hospital under doses of drachm ij to drachm iv per diem, the average residence in hospital being only eighteen days if four cases which became chronic are excluded, or 21.9 days if they are included.

The plan in vogue at our hospital here and in my own private practice is to give about 15 grains every two or three hours, according to the severity of the case and until the articular pain and pyrexia are relieved. After the pain and pyrexia have yielded, the remedy should be continued in smaller doses, say 10 to 15 grs., three or four times a day, according to the severity of the case, for eight to ten days longer, to prevent relapse, and during this period exposure, exercise, and dietetic excesses must be carefully guarded against.

The salicine may be given dissolved in milk or enclosed in wafers; the salicylate of soda, in a solution of any aromatic water, to which extract of liquorice or syrup of lemon and a few drops of spirits of chloroform may be added. The French add a little rum to flavor the mixture. Should severe cardiac inflammation exist, and, even although not severe, should there exist signs of failure of cardiac power, salicylates and salicine had better be avoided. If the secretion of urine diminish considerably under their use, or hæmaturia supervene, or organic disease of the kidneys exist, they must be employed cautiously, and may require prompt suspension. If marked debility exist, stimulants, especially the alcoholic, should be combined with them.

The oil of wintergreen has recently been well spoken of by F. P. Kinnicutt of St. Luke's Hospital, New York, as a substitute for salicylate sodium. It is itself a methyl salicylate 90 per cent., plus terebene 10 per cent. Its officinal name is oleum gaultheria, and it is given in doses of minim x-xv every two hours except during sleep, and in severe cases of articular rheumatism during the twenty-four hours, either by floating the oil upon a wineglass of water or milk or in capsules or upon lumps of white sugar. It resembles in its influence upon acute rheumatism very closely the sodium salicylate, for which it may perhaps be substituted, and Kinnicutt maintains that it is quite as effectual, pleasanter to take, and free from the intoxicating properties of the salt and the salicylic acid. It requires to be continued during convalescence just like the salicylate.

{60} The alkalies--in this country at least--were the favorite remedies in the treatment of acute articular rheumatism before the powers of salicine and salicylic acid became generally known, and there are still authorities who maintain their excellence, if not their superiority over the salicylates, in protecting the heart against the recurrence of rheumatic inflammation (Flint, Dickinson, Sinclair, Stillé).

Under the term the alkaline treatment unfortunately are included two distinct methods of administering the salts composed of potash and soda and the vegetable acids, carbonic, tartaric, citric, etc.--viz.: that in which about half a drachm of one of these salts is given three or four times a day; and the other known as Fuller's method, in which large doses are prescribed, so that from an ounce to an ounce and a half is given in the first twenty-four hours, with the view of rapidly rendering the urine alkaline, and if possible the perspiration also; for I have frequently produced the former effect in less than twelve hours, yet have found the perspiration still redden litmus on the second, and even the third, day and later. A disregard of the essential differences existing between these two methods of employing alkalies in acute rheumatism may partially account for the differences of opinion existing as to the value of the alkaline treatment, and for the differences in the statistical results thereof published by various observers--a remark applicable to other methods and statistics also. Fuller commonly ordered every three or four hours bicarb. sodium drachm iss and acetate of potassium drachm ss dissolved in ounce iij of water and rendered effervescing at the moment of administration by the addition of an ounce of lemon-juice or drachm ss of citric acid. As soon as the urine presents an alkaline reaction--which is usually the case in twelve to twenty-four hours--the quantity of the alkali is reduced by one-half, or to about 8 drachms, during the succeeding twenty-four hours, and provided the urine continues alkaline to 3 drachms on the third day. On the fourth day and subsequently only a scruple to half a drachm of alkali is given three times a day, sufficient to keep the urine alkaline, and to each dose are added 3 grains of quinia dissolved in lemon-juice; and this combination is continued till convalescence sets in. An aperient pill is given whenever needed, but is administered "only under conditions of extreme nervous irritation." The method is not an exclusively alkaline one.

Space will not allow of a lengthened analysis of the statistics that have been published on this subject, and I will give only some of the more important statistical results. While, as we have seen, the average duration of pyrexia and articular pain under salicylate treatment is about 5.4 days, under moderate alkaline treatment, according to the recent statistics of Finlay and Lucas, the average duration of pyrexia was 10.3 days and of articular pain 12.2 days, and of Owen 6.5 days for the first and 8 days for the second, or a general average for the pain and pyrexia together of 9.25 days, or about 3.85 days longer than under the salicylate treatment. Nor can it be said even of the full alkaline plan that the first or second dose frequently relieves the articular pains like a charm. On the other hand, it has been already shown that the average time spent in hospital was five days less under the full alkaline than under the salicylate treatment.

As regards the relative power of the salicylates and of full alkaline {61} treatment in protecting the heart, the following analysis and calculation deserve attention. The percentage of cases in which cardiac disease set in after the salicylate treatment began was, according to Powell, 18.75; according to Haviland Hall, 37.1; according to Finlay and Lucas, 11.60; Southey, 8; Brown, 4.76; Jacobi, 3.35, or a general average of 14 per cent.; whereas cardiac disease developed after the alkaline treatment had commenced in 13.6 per centum according to Blake; in 10.7 per cent. according to Dickinson; in 7 per cent. according to Owen; in 6.6 per cent. according to Finlay and Lucas; and in 2 per cent. according to Fuller; making a general average of only 7.8 per cent.

Judging from these statistics, it is not improbable that a combination of sodium salicylate, with full doses of bicarbonate of sodium or chlorate of potassium, will give better results in the treatment of acute rheumatism than either of those classes of remedies singly. Indeed, Flint and others have advised such combinations, and Bedford Fenwick has recently stated, as a result of his experience in 30 cases, that if, after giving a free purge, followed by scruple doses of sodium salicylate hourly for six hours, that salt be stopped, and in twelve hours afterward half-drachm doses of citrate of potassium be administered every four or six hours until the saliva becomes alkaline, relapses will be extremely rare, and that this is the safest and most successful method of treating acute and subacute articular rheumatism.

Having spoken somewhat fully upon the remedies of which I have most personal experience, and which have the largest number of advocates at the present time, and having advised the combination of these remedies, I shall only glance at some of the other remedies or methods of treating the disease still more or less employed.

Quinia, given in divided doses to the extent of 15 to 30 grains in the day, is still highly thought of in France in the early stages, during the course of and on the occurrence of relapses, in acute (especially febrile poly-) articular rheumatism. It is claimed by Briquet, Monneret, Legroux, and others that although not a specific for the disease it moderates the general disturbance, diminishes the local affections, and even retards the development or lessens the gravity of the cerebral symptoms--that, although it does not control the cardiac inflammations, it is not contraindicated by them. The only recent English authority who has strongly advocated full doses of quinia in this disease is Garrod, but he mixed the drug, in five-grain doses, with half a drachm of bicarbonate of potassium, a little mucilage, and spirits of chloroform, and gave it every four hours until the fever and articular affection had completely abated. Sufficient facts have not been published to permit of the formation of a reliable judgment as to the actual or the comparative value of either the simple quinia or the quino-alkaline treatment of acute and subacute articular rheumatism. There can be no doubt as to the value of quinia to meet certain conditions incident to the disease, such as debility, lingering {62} convalescence, periodical relapse, excessive perspiration, failure of appetite, and perhaps, in some instances, high temperature. Barclay has found quinia of much service when depression has followed the long continuance of the alkaline treatment and is attended with alkaline urine and a deposit of the earthy phosphates. It may be given by the rectum if not tolerated by the stomach or if the alkalines are being taken.

Greenhow has treated 43 cases with iodide of potassium and quinine, and says that his experience of this method contrasts favorably with that of salicine and salicylate of soda. However, pneumonia supervened in 3 cases while under treatment; cardiac inflammation arose in 6 cases (= 14 per cent.) after admission; single relapses of short duration occurred in 21 per cent.; and, excluding two cases in which the treatment was soon discontinued and 7 very mild cases, the remaining 34 cases were on the average each thirty-six days in hospital. Under this method relapses were less frequent (21 per cent. instead of 26 per cent.), and stay in hospital longer (36 instead of 30.4 days), than under that by the salicylates; but the number of cases treated is too small to base a final opinion upon. He prescribed 5 grains each of iodide of potassium and carbonate of ammonia three or four times a day, and 2 grains of quinia with three of extract of hyoscyamus in pill as often. This method, in principle at least, resembles that recommended by DaCosta, who administers in uncomplicated cases bromide of ammonium in 15- to 20-grain doses every three hours, and as soon as the acute symptoms have disappeared follows it by quinia in fair doses. It has not come into general use in this country, although its eminent proposer published his cases in 1869.

Notwithstanding the encomiums passed upon propylamine--or, more correctly, trimethylamine--as a remedy for acute and chronic rheumatism by Awenarius of St. Petersburg in 1856, by Gaston of Indiana in 1872, by Dujardin-Beaumetz in 1873, and Peltier in 1874 (both of France), and Spencer of England in 1875, it has not been much employed, especially since the salicylates have attracted attention. It appears that in a considerable proportion of cases the articular pains have subsided in two or three days under its employment, and then the temperature has declined, but the visceral complications have not been prevented. From 4 to 8 minims of trimethylamine in an ounce of peppermint-water, with a drachm of syrup of ginger, may be given every hour or two, the intervals to be increased as the pains diminish. When pain has quite ceased the drug may be stopped and quinia given its place. It merits further study in this disease, and Dr. Shapter of the Exeter Hospital has very recently stated that he is so convinced or the value of propylamine that salicylic acid has not fully commended itself to him. Senator has recently recommended benzoic acid or its sodium salt in large doses (about ounce ss in the day) in those cases of acute rheumatic arthritis in which {63} the salicylates have failed, although he admits that it scarcely rivals them. His 22 patients were relieved in 4.4 days as the average, and no complications occurred in any of them. Benzoic acid is said not to produce the nausea, depression, or unpleasant head phenomena of salicylic acid, to which it is closely related in chemical composition.

Space will not permit of any notice of lemon-juice, perchloride of iron, the mineral acids, or the blistering treatment. Of this last my experience enables me to say that it frequently relieves the pains promptly, but does not at all always protect the heart. In my opinion it deserves an extended employment in conjunction with early and full doses of the sodium salicylate. As Andrews has not by any communication made since the publication of his paper in 1874 maintained the value of the treatment of the disease by an exclusively non-nitrogenous diet of arrowroot, and as he had then treated but eight cases in that way, it is hardly necessary to consider it as a method of treatment.

Having spoken of the treatment of the general disease acute articular rheumatism, it remains to speak of the treatment of its visceral manifestations and of some of its more important incidental symptoms and complications. As the treatment of the various forms of cardiac inflammation will be given in extenso in the articles specially devoted to those topics, I will be very brief in my notice of them.