EXPERIMENTS 
TO DETERMINE 
THE INFLUENCE OF DIGITALIS ON NORMAL TEMPERATURES 
AND 
ITS ACTION AS AN ANTIPYRETIC IN TYPHOID FEVER. 
BY / 
V' 
JOSEPH LEI DY, Jr., M. D. 
(University of Pennsylvania). Resident Physician at University Hospital. 
[Reprinted from the Therapeutic Gazette for October 15, 1888.] 
DETROIT, MICH.; ' 
GEORGE S. DAVIS, PUBLISHES. 
1888. EXPERIM ENTS 
/ 
TO DETERMINE 
THE INFLUENCE OF DIGITALIS ON NORMAL TEMPERATURES 
AND 
ITS ACTION AS AN ANTIPYRETIC IN TYPHOID FEVER. 
THAT toxic doses of digitalis lower the 
temperature in healthy men and ani- 
mals, and that this fall is preceded by a tem- 
porary rise, has been proven experimentally 
by numerous observers. From the present 
state of our knowledge these phenomena ap- 
pear without doubt to be due to changes in 
the circulation. Clinical data, however, have 
been wanting as to the action of therapeutic 
doses in health and disease. The following 
results obtained from the administration of 
this drug in a series of cases in the medical 
wards of the University Hospital are of in- 
terest and importance : 
ditions. Absolute rest, bed-pan imperative, 
and perfect quiet insisted upon. No drug 
was administered directly to the heart, and 
careful attention was given to diet. 
In all the cases so treated the pulse, respi- 
ration, and temperature soon fell to normal. 
In most cases any slight rise upon admission 
was usually referable to the excitement at- 
tendant upon access to the hospital ward. In 
the majority of cases this mode of treatment 
sufficed. The temperature, pulse, and res- 
piration were then noted at regular intervals. 
Those cases which showed a normal range 
continuously for several days were selected. 
From the sixth to tenth day after admission 
the drug was administered either in the form 
of the tincture or infusion. The temperature, 
pulse, and respiration were then registered 
every one or two hours throughout its 
use. 
I. The first series of cases are recorded for 
the purpose of showing the action of thera- 
peutic doses upon normal temperatures. In 
seventeen cases of organic heart-disease with 
normal temperature the administration of 
digitalis was followed by a subnormal tem- 
perature, ranging from 96.3° to 97.8° through- 
out its use. 
Of seventeen selected cases in no instance 
could a rise in the temperature be detected. 
Upon admission the above cases were 
placed under the most perfect hygienic con- 
In all the cases, after the administration of 
digitalis, the temperatures became subnormal, Experiments to Determine the Influence of Digitalis on Normal Temperatures 
ranging between 96.2° and 97.8°, and remained 
so from one to two days after we ceased its 
administration. 
The following charts show its effect upon 
the heart, respiration, and normal tempera- 
ture in two of the cases under observation. 
In the first case, the infusion was used ; in the 
second, the tincture. Want of space prevents 
further reference. These appended, however, 
are types of the remaining charts. 
S3 
.2 
c5 
S3 33 
— ft 
Temperature. 
Date 
3 
d. 
M 
>>2 
ci 
p 
97 
0 98 
0 99 
Urine voided. 
Oct. 9 
8o 
3° 
7 
Morning 
M. 
a 
84 
26 
“ 
> 
Evening 
E. 
IO 
78 
26 
8 
M. 
“ 
78 
24 
“ 
Sxii 
E. 
11 
76 
28 
9 
Inf. digitalis, t. d 
M. 
it 
78 
28 
<< 
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12 
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M. 
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76 
22 
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> 
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E. 
14 
72 
3° 
12 
M. 
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74 
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E. 
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70 
20 
13 
M. 
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74 
24 
l( 
• • • < 
« 1 1 1 
E. 
16 
72 
26 
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M. 
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68 
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> 
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76 
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§xx 
Case I.—L. G. 
Case lI.—M. L. 
o3 
0 
Dec. 12 
(< 
13 
14 
15 
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16 
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17 
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6 
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(4 
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— cu 
Temperature. 
Urine voided. 
r 
0 
97° 98 
0 99° 
11 
(( 
12 
13 
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15 
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16 
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u 
M. 
M. 
Tinct. digitalis, t. d M. 
M. 
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“ r^r 
(III 
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. . 1 • • and its Action as an Antipyretic in Typhoid Fever. 
3 
11. The second series of cases are appended 
for the purpose of showing the action of ther- 
apeutic doses of digitalis upon the pulse, res- 
piration, and temperature in fever. 
The following temperature charts are se- 
lected from ten (ro) cases of typhoid, showing 
its action upon the pulse, respiration, and 
temperature curve. 
Case I.—J. M. 
: : • vo : 
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• is* . 00 O O to . . On 4^ 
: to • to to to to : ; to to 
. Os Q\ CO oc • • 00 4^ 
* 5 " tO ~ ~ ~ ~ 
Date. 
Pulse. 
Respiration 
Days in 
hospital. 
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• 4 “ 
8 “ 
Digitalis, 2 p.m. 
j 6 « 
Digitalis, 8 “ 
Digitalis, n\,xv. 2 a.m. 
Case lI.—C. P. 
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: o. . o • <y\ o o • : 
: ; ::: 
• . . • . •£-.-£*- : cj\ . owm. : 
~ - O “ " - - - " " " -vo - 00 
Date. 
Pulse. 
Respiration 
Days in 
hospital. 
: 
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1 Digitalis, rn xv 4 “ 
: 
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o 4 
Experiments to Determine the Influence of Digitalis on Normal Temperatures 
In six cases there was noted, besides a fall 
in the pulse and respiration, a decided fall in 
the temperature. 
the use of digitalis as an antipyretic in typhoid 
fever. 
Soon after the appearance of Wunderlich’s 
article, digitalis was used upon the Continent, 
but had few followers in England (Phillips). 
In three cases there was but a slight fall in 
the temperature. 
In one case no fall in the temperature was 
to be noted. 
Liebermeister (“ Ziemssen’s Encyclop.,” 
vol. iii.) has used it with asserted good re- 
sults in combination with the cold-water 
treatment. 
In nine cases the temperature fell from 1.50 
to 30 Fahr., and remained low throughout the 
course of the disease. 
Hankel {Arch. derHeilk.. 1869) gives results 
from its use as an antipyretic in an epidemic 
of typhoid fever. Though worthy of notice, 
he found his mortality was not diminished 
(twelve per cent.). 
The treatment of the above cases was ex- 
pectant in character,—rest, careful attention 
to diet, and alcohol. The heart was watched, 
and it was when the alcohol appeared to lose 
its effect, when the nervous system had lost 
all control of this organ, when the pulse was 
weak, rapid, dicrotic, small, and often inter- 
mittent, that digitalis proved itself the most 
powerful remedy we had resort to to meet 
this indication, and offered the most prom- 
ising results ; the pulse became slower, the 
respirations calmer, the delirium often ceased, 
and the whole condition of the patient changed. 
Hyperpyrexia was treated principally by 
sponging, and it was in just such cases where 
we had that condition described as a “ de- 
lirium of temperature,” where the tempera- 
ture oscillated with the application and with- 
drawal of cold, that digitalis proved its 
permanent antipyretic action, which was stim- 
ulating rather than depressing in character. 
Ringer (“ Handb. of Therap.”) found that 
digitalis reduces temperature, but that large 
doses were required. 
Lauder-Brunton found it useless. 
Trousseau (vol. iii.) claims that the anti- 
pyretic action of digitalis has not equalled in 
practice its therapeutic promises. 
With the idea that digitalis is an active an- 
tipyretic, it has been prescribed in various 
acute diseases with asserted good results. 
To use it entirely for this purpose we are 
justified in agreeing with those observers who 
assert that the field for digitalis is not fever. 
The result of these investigations lead us to 
conclude that the great indications for digi- 
talis in typhoid fever are,—first, a weak heart, 
for its stimulating action, and hyperpyrexia, 
associated with a weak heart, for its antipyretic 
action, and that a strong, full pulse is a con- 
traindication to its use, even though it be 
associated with a high temperature. 
In the above cases the drug was used 
primarily for its action upon the heart, and 
secondarily for its antipyretic action. 
A careful review of the literature of the 
subject discloses the fact that the use of digi- 
talis for its antipyretic effect is not new, 
though the literature is meagre; with the 
exception of Wunderlich’s article (“ Upon 
Typhoid Fever,” Manual of Medical Ther- 
mometry, Syd. Soc. Trans.) clinical observa- 
tion is conspicuous by its absence. 
It has been held that digitalis is only to be 
used in those cases in which there is no con- 
siderable degree of cardiac weakness, when 
the pulse is not yet extremely frequent, or at 
least pretty strong. 
Liebermeister holds that the rule for its 
application in fever is just the opposite to 
what it is in diseases of the heart; in other 
words, that the more frequent the pulse the 
less is digitalis indicated. 
Wunderlich’s conclusions were criticised 
(Wood), as the drug was administered 
during the third and fourth weeks of the 
fever, at a period when natural defervescence 
was likely to take place. 
The view that the impending paralysis of 
the heart is not prevented by the use of this 
drug, but rather favored thereby, must be at 
least tentative. 
In the cases recorded since the drug was 
given at varying periods during the course of 
the disease ; the pulse and temperature being 
our guide, the possibility of such an error must 
be excluded, as in the majority of cases it was 
given for rising temperatures, and frequently, 
when the administration was stopped for any 
time, the temperature showed a tendency to 
rise. 
It has been proven experimentally that as 
the blood-pressure rises the temperature falls, 
under the action of this drug ; clinical obser- 
vations corroborate this statement, and there 
can be no doubt that such is the antipyretic 
action of digitalis. This assertion is in ac- 
cord with the experiments of Heidenhain, 
who found that a rise in the blood-pressure 
invariably produced a fall in the tempera- 
Wunderlich {Arch, der Heilk., 1862) de- 
serves the credit of having first introduced and its Action as an Antipyretic in Typhoid Fever. 
5 
ture. That the antipyretic action of digitalis 
is produced through changes in the circula- 
tion there can be no doubt. 
V. Though a most powerful antipyretic in 
treatment of hyperpyrexia when associated 
with a weak heart, it should not, however, be 
used to meet this indication when there are 
no evidences of cardiac weakness,—i.e., when 
the pulse is strong, full, and bounding. 
From the above clinical observations it may 
be said that, therapeutically,— 
I. Digitalis depresses normal temperatures 
from one to one and a half degrees ; that this 
subnormal range remains from one to two 
days after the administration has ceased. 
Administration.—Both the tincture and in- 
fusion were used, preferably the tincture in 
typhoid fever and infusion in chronic heart- 
disease. We found no hesitation in using 
the tincture hypodermically in typhoid fever 
when the stomach refused to retain it. It 
has been used since the above cases were 
treated, in combination with quinine, and in 
addition to the cold-water treatment, with 
good results. 
In typhoid fever it may be said,— 
I. Digitalis reduces the pulse-rate, dimin- 
ishes the respirations, and depresses the tem- 
perature. 
11. That with a fall in the pulse and res- 
pirations there is a corresponding decline in 
the temperature. 
111. That a weak heart is no contraindica- 
tion to its use. 
In conclusion, the writer wishes to express 
his heartfelt thanks to Dr. William Pepper 
and Dr. William Osier for reference to the 
cases treated in their wards. 
IV. The main indication for its use is a 
weak heart, independent of hyperpyrexia.