S224

External Cooling in the Management of Fever

Peter Axelrod

Section of Infectious Diseases, Temple University School of Medicine,

Philadelphia

Although clinicians have used conductive, convective, and

evaporative methods of cooling to lower body temperature for
12500 years, the benefits of such treatments are uncertain even
to this day. More than 100 years ago, the German surgeon
Frederick von Esmarch wrote that some surgeons favored application of cold to inflamed tissues as a means of diminishing
blood flow to such tissues, whereas others recommended against
the practice because of concern that cold might have deleterious
effects on the skin [1]. One of the most commonly used physical
methods of treating fever before the advent of antipyretic drugs
was phlebotomy [2]. In 170 A.D., Galen wrote, . . . for I know
in some, up to 6 pints of blood were removed, so that the fever
was immediately extinguished and no impairment of strength
ensued [3].
Today, the two lingering questions regarding physical methods of antipyresis are whether the discomfort of physical cooling in young children is justified by a concomitant reduction
in complications of high fever, such as febrile seizures, and
whether external cooling of seriously ill, febrile patients is associated with lower morbidity than is treatment with antipyretic
drugs alone. The latter question arises because of the unwanted
side effects of physical methods of cooling, including induction
of shivering, hypermetabolism, sympathetic activation, and,
possibly, pneumonia, pressure sores, and other complications
that arise when sedating and paralyzing drugs are used for the
suppression of shivering.
Hyperthermia
External cooling is the treatment of choice for hyperthermia.
In contrast to fever, hyperthermia is characterized by a core
Reprints or correspondence: Dr. Peter Axelrod, Section of Infectious Diseases, Temple University Hospital, 3401 North Bond St., Philadelphia, PA
19140 (paxelrod@nimbus.temple.edu).
Clinical Infectious Diseases 2000; 31(Suppl 5):S2249
q 2000 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2000/3104S5-0012$03.00

temperature that exceeds the thermoregulatory set point. During fever, shivering, cutaneous vasoconstriction, and behavioral
responses raise core temperature to coincide with an elevated
thermal set point dictated by the action of endogenous pyrogens
in the thermoregulatory center. During hyperthermia, decreased heat production, vasodilation, sweating, and behavioral
cooling responses work to lower body temperature [4]. Thus,
when external cooling is used to treat hyperthermia, it is not
opposed by the counterregulatory processes that are evoked by
the use of such treatment for fever.
Exercise-induced hyperthermia is generally most effectively
managed by rapid cooling methods employing evaporation and
convection. An early study by Wyndham et al. [5] raised the
rectal temperatures of volunteers to 407C by means of exercise
in a hot environment. When subjects were cooled by wetting
the skin surface and blowing warm air across the body, the
mean rectal temperature decreased by 0.0717C/min; when they
were exposed to continuous sprays of water without forced air,
temperature fell at a rate of 0.0687C/min. Exposure to an ambient temperature of 217C resulted in a decrease of 0.0617C/
min; immersion in cold water (147C), a decrease of 0.0447C/
min; and exposure to ambient temperature of 33.97C, a decrease
of 0.0207C/min. In this study, immersion in cold water not only
failed to produce an optimal rate of cooling but was also the
only treatment to induce significant shivering. It was also the
only treatment that caused a drop in temperature after the
cessation of therapy (known as an afterfall), despite subjects
having taken a hot shower. Shivering persisted for as long as
1 h after immersion, and afterfalls ranged from 0.67C to 1.77C.
Weiner and Khogali [6] compared combined evaporation and
convection (a continuous spray of finely atomized water under
pressure combined with blown warm, cool, or cold air) with
cooling done by use of either a water mattress (207C) or a water
bath (157C) for the treatment of heatstroke. The combined
method that used warm air was the most effective, cooling at
a mean rate of 0.317C/min, compared with mean rates of

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Although physical methods of cooling are the treatment of choice for hyperthermia, their
value in the treatment of fever remains uncertain. Methods involving convection and evaporation are more effective than those involving conduction for the treatment of hyperthermia.
These same methods, combined with antipyretic medication, are preferable to immersion as
treatment for fever in young children but are generally not practical in adults. Febrile children
treated with tepid-water sponging plus antipyretic drugs are more uncomfortable that those
treated with antipyretic drugs alone, although they exhibit slightly more rapid reductions in
temperature. When febrile, seriously ill patients are externally cooled and are sedated or
paralyzed with drugs that suppress shivering, they may have a more rapid reduction of fever
and reduced energy expenditure than if treated with antipyretic drugs alone. A risk/benefit
assessment of the consequences of such treatment is not yet possible.

CID 2000;31 (Suppl 5)

Cooling and Fever Management

Adverse Metabolic and Physiologic Consequences

of External Cooling
In febrile patients, the capacity of external cooling to lower
core temperature may be limited because it induces both cutaneous vasoconstriction and shivering. The former effect has
been documented in a study of 19 healthy volunteers exhibiting
significant reductions in cutaneous fingertip blood flow in re-

sponse to cooling blankets [14]. A study of anesthetized volunteers also confirmed that when cutaneous vasoconstriction
is induced by external cooling, core body heat is conserved
because of diminution in normal cutaneous heat loss [15]. Numerous studies have shown that shivering in response to external cooling raises core temperature by increasing generation
of heat [16].
External cooling lowers skin temperature to a much greater
extent than it lowers core temperature, and it appears to initiate
vasoconstriction and shivering through its effect on skin temperature. Cheng et al. [17] have studied the relative contributions of core temperature and skin temperature to cutaneous
vasoconstriction and shivering. In their investigation, core temperature was controlled by adjusting the temperature of infused
iv fluids, and skin temperature was controlled by varying the
temperatures of air blown across the skin. As skin temperature
dropped, both vasoconstriction and shivering occurred at progressively higher core temperaturesthat is, skin temperature
was an independent trigger of these responses. Skin temperature
has also been shown to be as important as core temperature
in the determination of subjective thermal comfort [18].
Shivering not only impedes cooling during fever, it imposes
an additional metabolic burden. Studies in volunteers have
shown that shivering doubles oxygen consumption and respiratory minute volume, increases the percentage of carbon dioxide in expired air during exposure to cold, and increases the
respiratory quotient [19, 20]. It also increases sympathetic nervous system activity.
In a recent study of elderly patients undergoing thoracic or
abdominal surgery, half were randomized to an experimental
group in which forced air warming was used to prevent operative temperature decreases, and half were to randomized to
an experimental group receiving routine care [21]. The latter
subjects had lower core temperatures, higher serum levels of
norepinephrine and epinephrine, and more marked cutaneous
vasoconstriction than did the former subjects. In a study of
unanesthetized volunteers that compared the effects of infusion
of cool versus warm fluids, infusion of cool fluids induced a 7fold increase in norepinephrine levels, cutaneous vasoconstriction, an increase in mean arterial blood pressure, shivering, and
a rise in oxygen consumption [22]. In neither study was there
a change in cortisol levels in response to cooling. In another
study, fever was induced by IL-2 in human volunteers. Subjects
treated with forced cool air had more shivering and greater
oxygen consumption, higher levels of plasma epinephrine and
norepinephrine, increased mean arterial blood pressure, and
more discomfort than did those who were allowed to self-regulate skin temperature [23].

External Cooling of Febrile Children

External cooling in the form of liquids applied to the skin
is frequently used to treat fever in young children. The goal of

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0.137C/min with the use of atomized water and cool air, 0.127C/
min with atomized water and cold air, 0.117C/min with the cold
water bath, 0.107C/min with the water mattress, and 0.067C/
min when no treatment was given. The water bath caused continuous shivering and marked discomfort. Less-severe shivering
was seen among subjects treated with the water mattress and
among those treated with atomized water and cool air. The
authors concluded that the combination of evaporation and
convection was superior to conduction (cold immersion and
cooling blanket) for the treatment of hyperthermia, and that
treatment with cold air or water was counterproductive because
it induced shivering and cutaneous vasoconstriction. A more
recent study by Kielblock et al. [7] showed that ice packs placed
on the neck, axillae, and groin are ineffective in the treatment
of hyperthermia.
Few randomized trials of the treatment of heatstroke exist
[8]. Observational studies have established the efficacy of both
combined evaporation and convection and ice water immersion. However, both the age and the underlying conditions of
the patients studied have varied. Yaqub et al. studied 30 patients
who developed heatstroke during a pilgrimage to Mecca [9].
The age range of the patients was 3280 years. Some had coronary artery disease and/or were obese. The group had a mean
rectal temperature of 42.37C (range, 40.57C43.97C) before initiation of therapy, which consisted of sprays of water and air
at an ambient temperature of 207C. After initiation of therapy,
a mean time of 1 h was required to lower rectal temperature
to 38.57C. Ninety percent of subjects survived, and 83% did
not have sequelae. These results are equivalent to or better than
any results previously achieved for patients with illnesses of
similar severity [8, 10, 11].
In an observational study of heatstroke among runners participating in summertime races, Armstrong et al. [12] observed
more rapid cooling among subjects treated with ice water immersion than among those treated with wet towel wrappings
(both of which are essentially conductive cooling methods). The
subjects, all of whom were conditioned athletes (mean age, 35
years; range, 2365 years), were generally less ill than those
studied by Yaqub et al. [9]. Although iced peritoneal lavage has
been successfully used to treat a patient with hyperthermia unresponsive to evaporative cooling and iced gastric lavage [13],
the preferred treatment continues to be the use of cooling measures that involve a combination of evaporation and convection
[8].

S225

S226

Axelrod

Table 1.

Reference,
year

ence in the positive studies was 0.417C (range, 0.277C to

0.6757C), and that in the negative studies was 0.677C (range,
20.117C to 1.47C), implying that there is, at best, a small difference even during the first 30 min of therapy. Patient discomfort was assessed in 5 of the studies, with patients in the group
receiving combined therapy showing greater discomfort in all
5 studies. In the one study in which ice water and isopropyl
alcohol in water were used [32], both therapies produced extreme discomfort in 60% of patients, compared with 24%33%
of patients treated with tepid-water sponging and 9% of patients
treated with acetaminophen alone.
Therefore, for febrile children, the combination of sponging
and administration of antipyretic drugs appears to lower temperature slightly more rapidly during the first 30 min while
causing significantly more discomfort. As a result, combined
therapy cannot be justified on the basis of enhancing patient
comfort. It might be justified, nevertheless, if it reduced the
incidence of febrile seizures. Unfortunately, this effect has never
been demonstrated. Studies have shown that acetaminophen is
not effective in this regard [39, 40]. Therefore, it is unlikely that
the modest and transient improvements in temperature brought
about by combining sponging and administration of antipyretic
drugs are effective prophylaxis against febrile seizures. Nevertheless, a survey of 41 Internet sites advising parents on home
management of childhood fever found that 54% of sites recommended tepid-water sponging for the treatment of fever,
whereas only 2% discouraged such therapy [41].
Physical Cooling of Seriously Ill Febrile Patients
Data documenting the capacity of fever to increase morbidity
in patients with severe underlying conditions are sparse. Fever
has been reported to potentiate neurologic injury and brain
edema [4244], cardiac ischemia, and tissue hypoxia [45], and
to accelerate the terminal stages of fulminant infections
(through cytokine-induced tissue injury [46]). Fever also appears to increase the risk of fetal malformation and spontaneous abortion in pregnant women [45]. External cooling is
frequently administered in the hope that it will reduce the burden of these complications.
There are several reasons why antipyretic drugs might be
combined with external cooling to alleviate fever in seriously
ill patients. Many patients with cardiac conditions are obese,

Results of randomized studies of antipyresis in children: use of tepid-water sponging versus antipyretic drug therapy.

Cooling
n

[30] 1997

224

[31] 1997

80

Age, y

Initial temp., 7C

0.55

>39 (rectal)

0.54.5

39.540 (axillary)

Antipyretic drug

First 30 min

Aspirin, paracetamol,
ibuprofen
Paracetamol

Best with sponging

Sponging equivalent

Overall
Best with antipyretic drug
(37C difference at 3 h)
Best with antipyretic drug
(1.57C difference at 2 h)

Increased
discomfort
with physical
method
Not ascertained
No (qualitative)

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such treatment is to prevent febrile seizures and to relieve discomfort associated with the fever. Before the 1950s, sponging
was often performed with isopropyl alcohol or ethyl alcohol.
This practice was discouraged after it became apparent that
young children could inhale enough alcohol vapors during
treatment to develop hypoglycemia, become comatose, and die
[2427]. Despite recommendations to the contrary, however, the
practice is still used in certain communities in the United States,
and attendant morbidity continues [28]. Alcohol poisoning has
also been documented in an elderly adult who was treated with
an isopropyl alcohol sponge bath [29].
Two large, randomized trials comparing the use of tepidwater sponge baths with administration of antipyretics alone
for the treatment of young children with temperatures 138.97C
have recently been reported (table 1) [30, 31]. Both trials demonstrated the unequivocal superiority of antipyretic drugs for
the reduction of temperature within 23 h of initiation of treatment. However, antipyretic drugs appeared to work more
slowly than did tepid-water sponging. In one study, sponging
reduced temperatures more rapidly during the first 30 min; in
the other study, the two treatments produced equivalent reductions in temperature during the first 30 min. Differences in
patient comfort, in response to the two treatments, were not
assessed.
Although the use of sponge baths alone is clearly inferior to
administration of antipyretic drugs for the reduction of fever
over periods longer than 30 min after initiation of treatment,
they might still be of value if they potentiated the activity of
antipyretic drugs. Results of randomized trials comparing the
combination of antipyretic drugs and sponge bathing with the
use of antipyretic drugs alone have provided mixed results (table
2) [3238]. In 4 of 7 such studies reported to date, the combination treatment has been superior to the use of antipyretic
drugs alone for the reduction of temperature in febrile patients
overall, as well as for the reduction of temperature during the
first 30 min after initiation of therapy. In the remaining 3 studies, the treatments were equally effective in lowering temperature. The preponderance of evidence resulting from examination of the actual temperature plots presented in these
publications shows a more rapid reduction in temperature during the first 30 min of treatment when the use of sponging is
combined with administration of antipyretic drugs. When one
compares the temperature differences at 1 h, the mean differ-

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Cooling and Fever Management

S227

Table 2. Results of randomized studies of antipyresis in children: comparison of the use of sponging plus administration of antipyretic
drugs with administration of antipyretic drugs alone.
Reference,
year

Cooling

Initial temp.,
7C

Antipyretic
drug

[32] 1970

115

0.55

>39.4

Acetaminophen

Combination
superior

Combination superior: sponging

with ice water or alcohol and
water superior to sponging
with tepid water

[33] 1973

37

0.55

>39.5

No difference

No difference

[34] 1985

130

0.252

>39.0

Aspirin, paracetamol
Aspirin, acetaminophen

No difference
at 50 min

No difference

[35] 1990
[36] 1992

54
26

0.334
0.255

>38.9
a
37.839.9

[37] 1994

75

0.55

>38.5

Paracetamol

No difference
Combination
superior
Combination
superior

[38] 1997

20

0.56

>38.9

Acetaminophen

Combination superior at 60 min

Combination superior over 4 h,
but difference small
Combination superior for time to
reach temp. !387C; 10% have
fever rebound (temp. 1387C) in
combination group 0% in antipyretic group
No difference

Acetaminophen
Paracetamol

First 30 min

Combination
superior, first
hour

Overall

Increased discomfort
with physical method
Yes (quantitative): sponging
with ice water or alcohol
and water was more uncomfortable than that with tepid
water
No ascertained
Yes (qualitative): 7 children
were removed from the study
for shivering
Not ascertained
Yes (quantitative): by parent
assessment
Yes (quantitative): mainly crying; only 1 child shivered

Yes (quantitative)

NOTE. Temp., temperature. Sponging is with tepid water, unless otherwise indicated. Subjects in groups receiving placebo or sponging alone are excluded.
Temperatures are rectal unless otherwise indicated.
a
Axillary.

and the insulating effects of obesity impair heat dissipation [47].

Similarly, patients with diminished cardiac output or hypertension have reduced peripheral blood flow that might compromise
heat exchange at body surfaces [48]. There is conflicting evidence that individuals 165 years of age have a higher temperature threshold for sweating than do younger individuals [48].
Finally, many such patients are treated with medications that
decrease sweating (e.g., anticholinergics), increase heat production (e.g., CNS stimulants or lithium), or both [48].
In a recent comparison of the methods of antipyresis used
for neurologic patients [49], 21 febrile patients were randomized
to 1 of the following 3 treatment groups: acetaminophen only,
acetaminophen accompanied by tepid-water sponging, and
acetaminophen accompanied by use of hypothermia blankets
[49]. The mean time required for rectal temperature to decrease
to 37.87C was 100 min for patients in the group using hypothermia blankets and 144 min for the patients in the group
using sponging. The difference was not statistically significant.
The study design did not allow for comparison with the group
treated with acetaminophen only. Blanket use produced shivering significantly more frequently than did the other two treatments. In a separate study comparing the temperatures of 4
patients treated with hypothermia blankets, higher blanket temperatures cooled patients as well as lower blanket temperatures
did, and such treatment produced less discomfort and shivering
[50].
In a nonrandomized study, Poblete et al. [51] examined the

metabolic effects of external cooling by use of cloths soaked

in ice water on febrile mechanically ventilated, critically ill patients [51]. This treatment was compared with treatment with
iv antipyretic drugs. Externally cooled patients exhibited significantly lower core temperatures and lower daily energy expenditures than did those who were not subjected to external
cooling (1791 kilocalories/day vs. 2409 kilocalories/day). Manthous et al. [52] also observed a significant decrease in core
temperature and daily energy expenditure among critically ill
febrile patients after application of cooling blankets. In both
studies, patients received large doses of drugs (morphine plus
midazolam, and pancuronium/atracurium plus sedation, respectively) directed at inhibition of shivering. In a small pilot
study of 14 critically ill febrile patients, those receiving antipyretic drugs plus physical cooling were found to have lower
core temperaturesand systemic vascular resistance indexes
that were closer to normalthan those receiving antipyretic
drugs alone [53]. In this study, the use of drugs to stop patients
from shivering was not described.
In 1997, ODonnell et al. [54] reported the results of a survey
of hypothermia blanket use among 83 febrile, varyingly sedated, intensive care unit patients [54]. In their subjects, the
mean cooling rates were identical for patients treated with hypothermia blankets and those treated with antipyretic drugs
alone (0.0167C/h). The similar rates of cooling persisted even
after the authors controlled for potentially confounding clinical variables. Patients treated with blankets had significantly

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Age,
y

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Axelrod

greater to-and-fro temperature fluctuations and a greater risk

of overshoot hypothermia. Although frostbite had been reported previously as a potential complication of cooling blankets [55], this complication was not observed by ODonnell et
al. [54].

19.
20.

21.

Summary
22.

23.
24.
25.
26.
27.

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Physical cooling methods are clearly indicated for the treatment of hyperthermia, but their use for the treatment of fever
remains controversial because of their propensity to induce cutaneous vasoconstriction, shivering, sympathetic activation,
and, perhaps most importantly, discomfort. The ultimate value
of external corporeal cooling for the treatment of fever will
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