CARDIOPULMONARY CONSEQUENCES OF PYROGEN-INDUCED HYPERPYREXIA IN MAN

The period of temperature ascent (chill phase)
was characterized by a rather wide scatter of in-
dividual hemodynamic responses, Altschule and
associates (1, 2) mentioned alternate flushing and
blanching of the capillary bed as a visible demon-
stration of the vasomotor instability characteristic
of the chill phase. The unpredictable occurrence
and -severity of frank chills also contributes to
such instability. The only consistent cardiac re-
sponse during the chill phase was an increase in
heart rate. Others have noted that a rather con-
stant relationship exists between increase in car-
diac rate and temperature elevation (11).

The erratic hemodynamic behavior during the
chill phase contrasted with rather consistent re-
spiratory changes. There was a significant in-
crease in both minute and alveolar ventilation as-
sociated with a modest depression of arterial CO,
tension. The hyperventilatory response during the
chill phase appeared to be in excess of that needed
to meet the increased metabolic demands imposed.
by the rising temperature. The fact that alveolar
and minute ventilation both rose more sharply than
oxygen consumption and that mild hypocapnia ap-
peared both support this view. This hyperventila-
tion may serve as a prompt means to achieve heat
loss, as others have suggested (2, 5, 10). Previ-
ous workers have noted that alveolar hyperventila-
tion and hypocapnia are more marked and pro-
longed than reported here when temperature ele-
vation is achieved by methods which also block
heat loss from the skin, i.e., in thermal chambers or
in heated baths (5, 7, 26). That anxiety induced
by discomfort may also contribute to hyperventila-
tion cannot be discounted, however, since hyper-
ventilation was more pronounced among those
patients who experienced frank chills (Figure 6).

The flush phase was marked by consistent hemo-
dynamic and respiratory alterations. An increase
in cardiac output to 27% above the control level
was accompanied by a drop in mean brachial ar-
terial pressure but a rise in mean pulmonary ar-
terial pressure. This disparate behavior of sys-
temic and pulmonary arterial pressures suggests
that the peripheral and pulmonary vascular beds
do not participate equally in the vasodilation which
characterizes the flush phase. Calculated total
systemic resistance fell a significant 30% below
control levels, while total pulmonary resistance
was virtually unchanged. Since those wedge pres-

632

sures obtained showed no change from base-line
levels, it appears that the pulmonary arterioles,
unlike those in the skin, the kidneys (4), and the
splanchnic bed (22), do not dilate during the flush
phase of the pyrogenic reaction. Although our
data do not define the mechanism responsible for
differences in systemic and pulmonary vascular be-
havior, the possible role of serotonin release dur-
ing the pyrogen reaction mierits consideration (11,
27). Our studies in man contrast with Kuida’s
demonstration of marked postcapillary pulmonary
hypertension in animals (17). Aside from the
possible effects of species variation and quite dis-
similar experimental conditions, the differences
may be attributed to the fact that the doses of py-
rogen used by Kuida were massive when com-
pared to those used in the present study.

The increase in cardiac output during the flush
is accompanied by a parallel rise in cardiac rate.
This tachycardia may have special clinical impor-
tance in terms of cardiac efficiency (28).

The increase in oxygen uptake reached its peak
level during the flush phase, exceeding base-line
values by almost one-third. However, minute
ventilation and alveolar ventilation actually de-
cline slightly from the values observed during the
chill phase. This better parallelism between ven-
tilation and metabolic demand may reflect the les-
sened demand for respiratory heat loss as the con-
stricted, heat-retaining dermal vascular bed of the
chill gives way to the dilated, heat-losing dermal
bed of the flush phase. Thus, the alveolar hyper-
ventilation of the chill phase moderates, and hy-
pocapnia does not progress. Mean arterial oxy-
gen saturation does not change significantly from
base-line levels. Cullen, Weir, and Cook (6) had
indicated that significant arterial desaturation ac-
companied temperature elevation. Our data agree
with those of Gordon and associates (7, 26) and
Altschule and co-workers (1,2), who found no sig-
nificant decrease in saturation.

During the phase of defervescence there was a
gradual return toward base-line values. However,
some burden upon the cardiopulmonary apparatus
persisted. The heart rate remained significantly
elevated, and the increase in- pulmonary arterial
pressure persisted. The oxygen uptake, minute
ventilation, alveolar ventilation, and respiratory
rate all remained significantly elevated, and mild
hypocapnia continued.





629 KENNETH M. MOSER, RICHARD B. PERRY, AND PETER C. LUCHSINGER

The heart rate paralleled the temperature re-
sponse, being unchanged from control levels dur-
ing the prodrome, increasing significantly during
the chill (+ 19%), and remaining significantly
elevated during the flush (+ 27%) and deferves-
cent (+ 21%) phases. The calculated stroke
volume did not deviate significantly from control
levels during any study period.

Respiratory changes (Table II, Figure 3). The
oxygen uptake was essentially unchanged during
the prodrome, became significantly elevated above
control levels during the chill phase, reached a
peak level (+ 27%) during the flush, and re-
mained significantly elevated during deferves-
cence, Minute ventilation was unchanged during
the prodrome, rose significantly above control
levels during the chill phase (+ 29%) and re-
mained significantly elevated during the flush
(+ 26%) and defervescent (+ 25%) phases.
Alveolar ventilation followed a sequence that was
qualitatively identical to minute ventilation but
quantitatively greater. Respiratory rate was un-
changed during the prodrome, increased during
the chill, and rose significantly above control lev-
els during the flush and defervescent periods.

% CHANGE

FROM BASELINE
+30
+20

+10

-30 4 T T 3

3
STUDY

Fic. 2. CHAnces IN cARDIAc outruT (C.O.), MEAN
BRACHIAL ARTERIAL PRESSURE (BAM), AND MEAN PUL-
MONARY ARTERIAL PRESSURE (PAM) DURING PYROGEN
REACTION, Percentage of change, on ordinate; study pe-
riod, on abscissa (1 =control; 2= prodrome; 3= chill;
4= flush; 5=defervescence). Plotted data represent
group means. Open circles indicate changes which de-
viate significantly (p =< 0.05) from base-line values.

+50

+40

% CHANGE “3° a
FROM ve
BASELINE 420. RR
Vor

+10

°.

“10
' 2 3 4 5

sTuoY

Fic. 3. CHANGES IN OXYGEN UPTAKE (Vo;), MINUTE
VENTILATION (Vz), ALVEOLAR VENTILATION (Va), AND
RESPIRATORY RATE (RR). Same format as Figure 2.

The respiratory quotient, Vp/Vz ratio, and re-
spiratory equivalent (minute ventilation/oxygen
uptake) did not change significantly from control

- values during any study period. The tidal volume

was significantly increased during the chill and
remained elevated during flush and defervescence.

Arterial blood gas and pH changes (Table III).
Neither the arterial oxygen saturation nor the
carbon dioxide content deviated significantly from
control levels during any postpyrogen study pe-
riod. The calculated arterial carbon dioxide ten-
sion was unchanged during the prodrome, but
fell significantly below control values during the
chill, flush, and defervescent phases. The arterial
pH rose minimally above control values during the
chill, flush, and defervescent study periods.

The calculated alveolar oxygen tension and the
arteriovenous oxygen difference were essentially
unchanged during all study periods.

Chill versus no chill. With one exception, the
data revealed that no statistically significant dif-
ferences in hemodynamic, respiratory, or blood
gas responses existed between the five patients who
experienced frank chills and the five who did not.
The exception was the significantly greater in-
crease in alveolar ventilation during the chill phase
in subjects with frank chills (see Figure6). Other
quantitative differences (not statistically signifi-
cant) were noted. The group with frank chills
demonstrated a greater rise in mean brachial and
mean pulmonary arterial pressure, oxygen uptake,
and minute and alveolar ventilation during the
chill phase ; a greater fall in mean brachial arterial
pressure during the flush phase; and a greater


633

Clinical implications of pyrogen reaction. The
data presented clearly indicate that even the small
doses of pyrogen used in this study impose an
acute burden upon the cardiorespiratory appara-
tus. Despite the moderate degree of temperature
elevation induced in these patients, they demon-
strated increases in cardiac output, heart rate,
oxygen uptake, and minute and alveolar ventila-
tion in excess of 25% above base-line values.
Furthermore, significant increases in the latter
four appeared during the chill phase and persisted
more than an hour after the temperature had be-
gun to decline from its peak level. The clinical
implications of these observations are clear. The
acute demands imposed by a pyrogen reaction may
be capable of provoking cardiac or respiratory
failure in patients with diminished cardiac or pul-
monary function.

The potential systemic hypotensive effect of
pyrogens in normal subjects is also worthy of
mention. Bradley, Chasis, Goldring, and Smith
(4) have previously shown that this systemic hy-
potension can be quite marked and prolonged in
hypertensive patients.

The extent of cardiopulmonary alterations elici-
ted by these modest temperature increments con-
firms the experience of others that temperature
elevation and pyrogen reaction are not equivalent
terms (4, 11,21). Although temperature changes,
when present, can be used as a guide to the phases
of the pyrogen reaction, the degree of temperature
elevation is not a reliable guide to the degree of
physiologic stress being imposed. Nor does the
absence. of significant fever in a patient exposed
to some source of pyrogen assure that he will es-
cape the cardiorespiratory alterations we have de-
scribed. Furthermore, as Cranston (11) has
stated, “it would appear unlikely that treatment
with antipyretics should have much effect on car-
diac failure induced by pyrogens.” The current
investigation indicates that this statement may be
equally valid for patients with pyrogen-induced
respiratory failure.

SUMMARY

1. Detailed cardiopulmonary studies were car-
ried out in ten male subjects free of overt cardio-
pulmonary disease before and at four intervals af-
ter intravenous injection of a pyrogenic lipopoly-
saccharide extract of gram-negative bacilli.

KENNETH M. MOSER, RICHARD B, PERRY, AND PETER C. LUCHSINGER

2. Four phases of cardiopulmonary response
could be identified following pyrogen injection cor-
responding to periods of stable temperature (pro-
drome), of rising temperature (chill), of peak
temperature (flush), and of temperature return
toward normal (defervescence).

3. No significant cardiopulmonary alterations
occurred during the prodrome.

4. During the chill, flush, and defervescent
phases, there was a significant elevation above con-
trol values in oxygen uptake, minute and alveolar
ventilation, respiratory rate, and cardiac rate. A
significant increase in cardiac output during the
flush phase was associated with an increase in
mean pulmonary arterial pressure but a decline in
systemic pressure, indicating a difference in be-
havior of the pulmonary and systemic vascular
beds.

5. The data indicate that the degree of tempera-
ture elevation cannot be used as a reliable guide
to degree of cardiac or respiratory alteration in-
duced by a pyrogen reaction.

6. It is concluded that the acute cardiopulmo-
nary burdens imposed by a pyrogen reaction may
be of sufficient magnitude to promote decompen-
sation in patients with compromised cardiac or
respiratory function.

REFERENCES

1. Altschule, M. D., A. S. Freedberg, and M. J. Mc-
Manus. Circulation and respiration during an epi-
sode of chill and fever in man. J. clin. Invest. 1945,
24, 878.

2, Altschule, M. D., and A. S. Freedberg. Circulation
and respiration in fever. Medicine (Baltimore)
1945, 24, 403.

3. Grollman, A. Variations in the cardiac output of
man. V. The cardiac output of man during the
malaise and pyrexia following the injection of ty-
phoid vaccine. J. clin. Invest. 1929, 7, 25.

Bradley, S. E., H. Chasis, W. Goldring, and H. W.
Smith. Hemodynamic alterations in normotensive
and hypertensive subjects during the pyrogenic
reaction. J. clin. Invest. 1945, 24, 749.

5. Wakim, K. G. The physiologic effects of heat. J.

Amer. med. Ass. 1948, 138, 1091.

. Cullen, S. C., E. F. Weir, and E. Cook. The rationale
of oxygen therapy during fever therapy. Arch.
phys. Ther. (Omaha) 1942, 23, 529.

7. Gordon, E. E., R. C. Darling, and E. Shea. Effects

of physical hyperthermia upon blood gas equilibria
in man. J. appl. Physiol. 1949, 1, 496.

8. Osborne, S. L. Effect of hyperpyrexia on the blood

pH. Arch. phys. Ther. (Omaha) 1941, 22, 17.

>

a


Reprinted from
Journal of Clinical Investigation
Vol. 42, No. 5, 1963

CARDIOPULMONARY CONSEQUENCES OF PYROGEN-INDUCED
HYPERPYREXIA IN MAN *

By KENNETH M. MOSER, RICHARD B, PERRY, anv PETER C. LUCHSINGER

(From the Department of Medicine, Pulmonary Division, Georgetown University Medical
School, and the Cardiopulmonary Laboratory, District of Columbia General Hospital,
Washington, D. C.)

(Submitted for publication June 6, 1962; accepted January 10, 1963)

The physiologic consequences of hyperpyrexia
attracted. considerable interest when artificially-
induced fever was a popular therapeutic maneuver
(1-10). Although induced hyperpyrexia has
lapsed from therapeutic favor, the effects of body
temperature elevation in response to infection, en-
vironmental factors, or pyrogenic drugs remain
a source of concern, especially in patients with
cardiac or pulmonary dysfunction.

Prior investigations have indicated that fever,
whether induced by external heating or pyrogen
injection, is accompanied by significant cardiac
and peripheral hemodynamic alterations in both
animals and man (1-4, 10, 11). However, data
concerning respiratory gas exchange, pulmonary
hemodynamics, and arterial blood gas composition
in hyperpyrexia are rather fragmentary and incon-
clusive (7-9, 12-17).

The purpose of this study was to evaluate si-
multaneously the changes in body temperature,
pulmonary and systemic hemodynamics, respira-
tory gas exchange, and arterial blood gas com-
position that occur in normal subjects after the
intravenous injection of a pyrogenic lipopolysac-
charide extract of gram-negative bacilli. Since
prior studies in man have not included cardiac
catheterization and detailed measurement of re-
spiratory function, it was felt that an investigation
using the techniques now available would shed
further light upon the cardiopulmonary conse-
quences of the pyrogenic reaction in man.

MATERIALS AND METHODS

Ten male subjects ranging from 33 to 74 years of age
(mean 45.6) were studied. All were free of cardiac
and pulmonary disease by clinical and routine laboratory
criteria. All subjects were studied in the morning after

* Aided by grants H-3114 and H-6236 from the Na-
tional Institutes of Health, Bethesda, Md.

an overnight fast. No sedation was employed prior to or
during the test period.

The pulmonary artery was catheterized under fluoro-
scopic guidance via the brachial vein, and a Cournand
needle was placed percutaneously in the contralateral
brachial artery. Pressure measurements were carried
out with Statham strain gauges and recorded with a mul-
tichannel Electronics-for-Medicine - photographic unit.
Mean pressures were determined by electronic integra-
tion. Cardiac output was determined by the Fick prin-
ciple. Expired air was collected for 5 minutes in a
Douglas bag with blood samples obtained simultaneously
from brachial artery and pulmonary artery at the mid-
point of the air collection. Expired air samples were
analyzed for oxygen and carbon dioxide in the Scholander
apparatus (18). Duplicate checks within 0.02% were
required. Blood oxygen content and capacity were de-
termined in the Haldane apparatus (15). Duplicate
checks within 0.2 vol % were required. Blood carbon
dioxide content was determined in the Van Slyke ap-
paratus with duplicate checks within 0.2 vol % required.
Determination of blood pH was carried out anaerobically
by using a Cambridge pH meter and a capillary glass
electrode with water jacket. Temperature of the water
perfusing the jacket during’ pH measurement was brought
to within + 0.1° C of the body temperature present at
the time of sample withdrawal by a Haake temperature-
pump system, Rectal temperature was continuously moni-
tored by an indwelling rectal thermocouple and a Yel-
low Springs Telethermometer unit. Respiratory rate
was directly counted. Cardiac rate was determined by
standard limb lead electrocardiograms. Vascular re-
sistances were calculated with the following formulas:

tolal pulmonary resistance = Pan cemtOxe
and
BAm (mm Hg) X 80

Q (L/min) *

Arterial Pco, was calculated from the Henderson-Has-
selbalch equation, with a pK,’ and solubility factor cor-
rected for body temperature (7, 15). Pao, was calcu-
lated from the alveolar air equation (15).

Five studies were carried out in each patient. Study
1 (control) was carried out fifteen minutes after intro-
duction of the cardiac catheter and brachial artery needle,
but prior to pyrogen injection, After this study, 0.45 ag

lotal systemic resistance =

626



10.

18.

19,

. Ferguson, C., and M. Buckholtz.

. Cranston, W. I.

. Koehler, A. E. Acid-base equilibrium.

. Luchsinger, P. C., and K. M. Moser.

CARDIOPULMONARY CONSEQUENCES OF PYROGEN~INDUCED HYPERPYREXIA IN MAN

Effect of hyper-
pyrexia on the pH figure of the blood. Arch.
phys. Ther. (Omaha) 1941, 22, 333.

Scholmerich, P., E, Kochn, and W. Offerman. Der
Kreislauf im Fieber. Arch. phys. Ther. (Lpz.)
1958, 8, 144,

Fever: pathogenesis and circula-

tory changes. Circulation 1959, 20, 1133.

. Bazett, H. C. Studies on the effects of baths on

man. I. Relationship between the effects pro-

duced and the temperature of the bath. Amer. J.

Physiol. 1924, 70, 412.

I. Clinical

studies in alkalosis. Arch. intern. Med. 1923, 31,
590.

Landis, E. M., W. L. Long, J. W. Dunn, C. L. Jack-
son, and U. Meyer. Studies on the effects of baths
on man. III. Effects of hot baths on respiration,
blood and urine. Amer. J. Physiol. 1926, 76, 35.

Respiration.

Physiologic Principles and Their Clinical Appli-

cations, English ed. St. Louis, Mo., C. V. Mosby,

1960, pp. 164-167.

. Gore, L, and H. H. Isaacson. The pathology of hy-

perpyrexia. Amer, J. Path. 1949, 25, 1029.

. Kuida, H., L. B. Hinshaw, R. P. Gilbert, and M. B.

Effect of gram-negative endotoxin on
Amer. J. Physiol. 1958,

Visscher.
pulmonary circulation,
192, 335.

Scholander, P. F, Analyzer for accurate estimation of
respiratory gases in one-half cubic centimeter
samples. J. biol. Chem. 1947, 167, 551.

Wendt, F., E. S, Snell, F. Goodale, Jr., and W. 1.
Cranston, Measurement of the human febrile re-

20.
21.

22.

23.

24,

25.

26.

27.

634

sponse to a bacterial pyrogen.
485.

Moser, K. M., and G. C. Hajjar. Unpublished data.

Bennett, I. L., Jr., and P. B. Beeson. The properties
and biologic effects of bacterial pyrogens. Medicine
(Baltimore) 1950, 29, 365.

Hamrick, L. W., Jr., and J. D. Myers. The effect
of subfebrile doses of bacterial pyrogens on
splanchnic metabolism and cardiac output. J. Lab.
clin. Med. 1955, 45, 568.

Gerbrandy, J., E. S. Snell, and W. I. Cranston. Oral,
rectal, and oesophageal temperatures in relation
to central temperature control in man. Clin. Sci.
1954, 13, 615.

Benzinger, T. H. The quantitative mechanism and
the sensory receptor organ of human temperature
control in warm environment. Ann. intern. Med.,
1961, 54, 685.

Gerbrandy, J. W. I. Cranston, and E. S. Snell. The

jal process in the action of bacterial pyrogens
in man, Clin, Sci, 1954, 13, 453.

Gordon, E. E., R. C. Darling, and E. Shea. An
evaluation of the question of anoxia in fever
therapy. Arch. phys. Med. 1949, 30, 154.

Davis, R. B., W. R. Meeker, and D. G. McQuarrie.
Immediate effects of intravenous endotoxin on
serotonin concentrations and blood platelets. Cir-
culat. Res. 1960, 8, 234.

Clin. Sci. 1956, 15,

. Maxwell, G. M., C. A. Castillo, D. H. White, Jr.,

C. W. Crumpton, and G. G. Rowe. Induced
tachycardia: its effect upon the coronary hemody-
namics, myocardial metabolism and cardiac effi-
ciency of the intact dog. J. clin. Invest. 1958, 37,
1413.

Dr. Moser is Chief, Pulmonary Function Laboratory, Georgetown Clinical
Research Institute, Federal Aviation Agency, Washington, D.C.

PO 882-974



627

3.04

.
a
t

.
°
i

RISE ABOVE BASELINE TEMPERATURE (°C)

KENNETH M. MOSER, RICHARD B, PERRY, AND PETER C. LUCHSINGER

1.54

1.04

0.54

OR too toot
30 60 90 120 150 180 210 240 270 300
TIME IN MINUTES AFTER PYROGEN ADMINISTRATION

Fic. 1, TEMPERATURE RESPONSE TO PYROGEN INJECTION. Middle curve

represents group mean; upper and lower curves indicate range.

Arrows in-

dicate time of prodrome (2), chill (3), flush (4), and defervescent (5)

phase studies.

of a pyrogenic lipopolysaccharide extract of gram-nega-
tive bacilli! was administered intravenously. Study 2
(prodrome phase) was carried out approximately 30
minutes after pyrogen injection, at which time no pa-
tient had a temperature elevation above 0.1° C. Study 3
(chill phase) was begun 30 minutes after an upswing of
the temperature curve was established, except in five
patients who had frank chills at this time. In these sub-
jects, study 3 was delayed for at least 15 minutes after
cessation of the chill, Study 4 (flush phase) was car-
ried out after rectal temperature had reached and sta-
bilized at its peak level for at least 15 minutes. Study
5 (defervescent phase) was carried out approximately
60 minutes after the temperature had begun to decline
from its peak value.

RESULTS

Data obtained during the prodrome, chill, flush,
and defervescent phases were compared with data
obtained during the control period. In addition,

1 Kindly supplied as Pyrexal by the Wander Com-
pany, Chicago, Ill.

data from the five patients who experienced chills
were compared with those from the five subjects
without chills. Differences between control and
subsequent study periods and between the chill
and no chill groups, with “p value” of 0.05 or less,
are referred to below as “significant,” although
statement of statistical significance does not imply
physiologic significance. Data derived during the
chill and defervescent phases should be viewed with
recognition that these phases, by the nature of the
investigation, were not “steady states.”

Temperature response (Figure 1). The tem-
perature response showed rather wide individual
variation in regard to time of onset, rate of ascent,
peak level, duration of peak level, and rate of de-
scent. All patients developed temperature ele-
vation of some degree. The mean peak tempera-
ture achieved during the flush phase was 1.5° C
(2.7° F) above base line.


CARDIOPULMONARY CONSEQUENCES OF PYROGEN-INDUCED HYPERPYREXIA IN MAN

TABLE I
Hemodynamic changes during pyrogen reaction*

628

Study period
1 2 3 4 5
C.O. 6.49 (0.65) 6.74 (0.78) 7.43 (0.88) 8.26 (0.61)t 6.67 (0.36)
BAm 905° (4:1) 94:2 (3:8) 49 (5.0) 79.1 (4.5) 85.4 (4.2)
PAm 16.1 (1.2) 16.0 (0.9) 17.3 (2.2) 19.3 (1.6)t 19.0 (1.3)t
TSR 1,115:0 (117 1,118.0 (134) 1,0650 (146) 766.0 (67)F 1,024.0 (82)
TPR 198.0 (33) 190.0 (29) 194.0 (23) 187.0 (20) 228.0 (16)
HR. 77.0 (3) 77.0 (3) 92:0 (6)E 98.0 (4)t 93.0 (4)t

*C.O, = cardiac output (1 per minute); BAm = mean brachial arterial pressure (mm Hg); PAm = mean pulmo-

nary arterial pressure (mm Lg);

TSR = total systemic resistance; TPR = total pulmonary resistance; H.R. = heart

rate. Values given are group means with standard error of mean in parentheses.

Differences significant at-0.01 level.
t Differences significant at 0.05 level.

Hemodynamic changes (Table I). Changes in
cardiac output were variable during the prodrome,
chill, and defervescent phases, but a significant
elevation above control levels (average, + 27%)
occurred during the flush.

Mean brachial arterial pressure did not change
appreciably during the prodrome and chill phases,
fell 14% below control levels during the flush
phase, and rose toward base-line values with defer-
vescence. Mean pulmonary arterial pressure
showed no significant changes during the pro-
drome and chill phases. In contrast to the sys-
temic pressure, however, pulmonary arterial pres-
sure rose significantly above control values during
fiush and defervescence (Figure 2). This dis-
parity in systemic and pulmonary pressure altera-

tions was reflected in the respective resistance cal-
culations. Total pulmonary. vascular resistance
remained essentially unchanged from control val-
ues during all phases, although a modest rise was
noted during defervescence. Total systemic re-
sistance fell significantly below control values dur-
ing the flush (— 31%) and remained slightly de-
pressed during defervescence.

The “wedge pressure” was measured in six pa-
tients during the control period, in two during the
prodrome, in one during the chill phase, in six
during the flush, and in seven during deferves-
cence. All values were below 10 mm Hg. No
increase greater than 2 mm Hg or decrease greater
than 3 mm Hg from control values occurred in any
patient,

TABLE II
Changes in respiratory behavior during pyrogen reaction*

Study period
1 2 3 4 5

Vor 245.0 (27) «240.0 (10) «289.0 (22)t 311.0 (18)t 290.0. (15)t

Ve 9,525.0 (665) 9,160.0 (650) 12,315.0 (1,395)t 1,970.0 (800)+ 1,885.0" (1,065)t

Va 4,775.0 (420) 5,175.0 (440) 6,740.0 (940) 6,230.0 (520) 6,070.0 (120)t

Vo 4,740.0 (370) 4,425.0 (385) 5,485.0 (560) 5,745.0 (650) 5,685.0 (515)

RR 20.0 (1.4) 19.6 (1.5) 21.4 (1.6) 234 (1.2)f 23.5 (1.8)f

RE. 39.0. (2) 38.0 (2) 43.0 (2) 39.0 (2) 41.0 (2)

TN. 495.0 (37) 476.0 (29) 606.0. (83)t 518.0 (50) 528.0 (50)

Vb/Ve .50 (.02) 48 (.03) AT (.03) AT (.02) 49 (.03)

RQ 0.91 (.03) 0.89 (0.2) 0,95 (.01) 0.85 (.01) 0.88 (.04)

*Vos = oxygen uptake (cubic centimeters per minute, STPD); Ve = minute ventilation (cubic centimeters per
minute, BTPS); Va = alveolar ventilation (cubic centimeters per minute, BTPS): Vo =. dead space ventilation (cubic
centimeters per minute, BTPS) ; R.R. = respiratory rate; R.E. = respiratory equivalent (Vz/Vo:); T.V. = tidal volume;

Vp/Ve = dead space to minute ventilation ratio; and RQ)= respiratory quotient. Values

standard error of mean in parentheses.
Differences significant at 0.01 level.
Differences significant at 0.05 level.

given are group means wit’