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;[159] Owen, 23; Brown, 21.9;[160] or a general
average of 30.4 days for the salicyl remedies. Under full alkaline
treatment: Owen, 26 days; Dickinson, 25;[161] Fuller, 22.2;[162]
Blakes, 24;[163] 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.
[Footnote 159: _Lancet_, ii., 1879, 420.]
[Footnote 160: _Boston Med. and Surg. Journ._, Feb., 1877. The four
cases excluded by the reports are included in this calculation, that it
may more fairly be compared with other reports.]
[Footnote 161: _Lancet_, i., 1869.]
[Footnote 162: _The Practitioner_, i., 1869, p. 137.]
[Footnote 163: _Boston City Hospital Reports_, 1st Series.]
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[164] 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%.
[Footnote 164: _The Lancet_, ii., 1881, 1120.]
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[165] cases
elimination was not completed before the fifth day, and not before the
eighth in Byanow's case.[166] Possibly uræmia may in some cases cause
the delirium.[167] 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,[168] Charles Barrows[169] 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.[170] 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[171] 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[172] 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,[173] 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[174]
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.
[Footnote 165: _Lancet_, i., 1882, 135.]
[Footnote 166: Quoted by Wood in his _Therapeutics and Mat. Med._,
1880, from _Centralb. für Chir._, 1877, 809.]
[Footnote 167: See DaCosta's observations in _Am. Med. Journal_, vol.
lxix., and Ackland's in _B. Med. Journal_, i., 1881, 337.]
[Footnote 168: _Boston Med. and Surg. Journal_.]
[Footnote 169: _N.Y. Med. Record_, April 29, 1882, 456.]
[Footnote 170: Köhler, _Centralb. f. Med. Wissensch._, 1876, and
Dunowsky, _Arbeiter Pharm. Labor._, Moskau, i. p. 190, quoted by H. C.
Wood, _Therapeutics, Mat. Med., etc._, 3d ed., p. 639.]
[Footnote 171: _Clin. Soc. Trans._, xiii. p. 266, c. iii.]
[Footnote 172: _Ibid._, p. 123.]
[Footnote 173: Quoted by D. Seille, Thèse, _De la Méd. Salicylée dans
le Rheumatism_, Paris, 1879, p. 54.]
[Footnote 174: _Clin. Soc. Trans._, x. p. 70, 1877.]
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.[175]
[Footnote 175: Isambard Owen, _Lancet_, ii., 1881, p. 1081.]
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[176] and Charteris[177] state that they have never seen
salicine, even in large doses, cause delirium; and Prof. Gairdner has
not found it produce any unfavorable symptoms.[178] On the other hand,
Greenhow[179] 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.
[Footnote 176: _Handbook Therapeutics_, 8th ed., 1880, 587.]
[Footnote 177: _Brit. Med. Jour._, i., 1881, 229.]
[Footnote 178: _Lancet_, i., 1882, in table giving experience of
British hospitals, prepared by Maclagan.]
[Footnote 179: _Trans. Path. Soc._, xiii. 262.]
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[180] 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[181] found that 10 to 15 grs.
every one, two, or three hours are sufficient.
[Footnote 180: _Lancet_, ii., 1881.]
[Footnote 181: _Dub. Journ. Med. Sci._, Sept., 1880, 193.]
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,[182] 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.
[Footnote 182: _Med. Record of New York_, Nov., 1882, 505.]
{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,[183] the average duration of
pyrexia was 10.3 days and of articular pain 12.2 days, and of Owen[184]
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.
[Footnote 183: _Lancet_, ii. 1879, 420.]
[Footnote 184: _Ibid._, ii., 1881, 1081.]
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;[185] in 10.7 per cent. according to Dickinson;[186] 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.
[Footnote 185: _Med. and Surg. Reports of Boston City Hospital_, 1st
Series, 1870.]
[Footnote 186: This percentage is obtained by adding together all the
cases treated by alkalies given by Dickinson in his IX., X., XI., and
XII. tables. Their total was 65 cases in which the heart was affected
seven times. In table IX. from drachm ii-iv of alkaline salts were
given daily, and in table X. about drachm iij daily.--_Lancet_, i.,
1869.]
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.[187]
[Footnote 187: _Lancet_, i., 1882.]
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,[188] 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,[189] 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.[190] It may be given by
the rectum if not tolerated by the stomach or if the alkalines are
being taken.
[Footnote 188: _La Goutte et le Rheumatisme_, Paris, 1857.]
[Footnote 189: Reynolds's _Syst. Med._, 1870, p. 951.]
[Footnote 190: _St. George's Hospital Reports_, vol. vi. p. 111 _et
seq._]
Greenhow[191] 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.[192]
[Footnote 191: _The Lancet_, i., 1882, 913.]
[Footnote 192: _Pennsylvania Hospital Reports_, vol. ii., 1869; _New
York Medical Record_, September, 1874, p. 481.]