Hyperthermia During Anesthesia
Lawrence J. Saidman, MD, Everette S. Havard, MD, and Edmond I. Eger, II, MD
The development of hyperthermia in an anesthetized
beserious threat to the patient's life. Once
patient can a
the temperature rise begins, it proceeds at an ever in-
creasing rate. It may go unrecognized until a sudden de-
terioration in the patient's condition calls attention to his
plight. The physiologic abnormalities associated with the
hyperthermia include dehydration, hypotension, hypoxia,
and acidosis. Treatment must be prompt if irreversible
tissue damage or death are to be avoided, and includes
rapid cooling, rehydration, and correction of the elec-
trolyte and acid-base abnormalities. Prevention must in-
clude adequate evaluation and treatment of preoperative
temperature elevations and hypermetabolic states. Use
of intraoperative temperature monitoring would enable
the anesthesiologist to recognize and treat the elevated
temperature before it climbed seriously high and led to
physiological decompensation.
Hyperthermi
threatening
a occurring
tient is an
infrequent
condition. If
in an anesthetized pa
but
potentially
recognized
life
and treated
early in its development, the patient can be re
turned to a euthermic state relatively easily. How
ever, the condition is often not recognized until an
extreme temperature increase with profound circula
tory depression and death or irreversible central
nervous system damage has occurred. Several cases
of hyperthermia culminating in death are reported
in the literature.1'4 A consistent pattern of tempera
ture rise (very rapid once started) occurred in two
cases of profound hyperthermia.
Report of Cases
Case 1.A 47-year-old white male in good health was
admitted for ventral herniorraphy. Past history was un
remarkable and included an uneventful anesthetic for
hiatus hernia repair. Physical examination revealed an
obese yet muscular male 217 lb (98.5 kg), 5 feet 8 inches
(173 cm), who was otherwise normal. He was premedi
cated with 0.8 mg of atropine given intramuscularly, and
arrived in the operating room with a temperature of 97.3 F
(36.3 C), blood pressure (BP) of 110/80 mm Hg, and pulse
rate of 74 beats per minute. Anesthesia was induced and
maintained with nitrous oxide and oxygen (4:2 liters per
minute), and halothane 1% via a cuffed endotracheal tube
utilizing a partial rebreathing system. Relaxation was ac
complished with the aid of a 0.2% succinylcholine chloride
From the Department of Anesthesia, University of California,
San Francisco Medical Center.
Read before the Section on Anesthesiology at the 113th Annual
Convention of the American Medical Association, San Francisco,
June 23, 1964.
Reprint requests to Department of Anesthesia, University of
California Medical Center, San Francisco 94122 (Dr. Saidman).
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drip. Sixty minutes after surgery began the patient was
noted to be diaphoretic, and requiring increasing amounts
of relaxant. The carbon dioxide canister was found to be
operating normally, but was nevertheless changed. Naso-
pharyngeal temperature 30 minutes later was 101.5 F
(37.5 C). The diaphoresis continued with otherwise normal
vital signs until one hour later when his BP suddenly fell
from 110/70 to 40/0 mm Hg with the pulse rate rising to
140 beats per minute. Respiration became inadequate at
this time. Metaraminol bitartrate, 5 mg, was given intra
venously in divided doses without any rise in BP. Esopha-
geal temperature at this time was 108.5 F (42.5 C) as
shown in the Figure. Anesthesia was immediately discon
tinued and 100% oxygen was administered via a nonre-
breathing valve.
An ampule, 44.6 mEq, of sodium bicarbonate (NaHCOa)
and prednisolone, 40 mg, were given intravenously. The
patient was packed in ice and 3,000 cc of lactated Ringer's
solution was infused rapidly. An arterial blood sample
revealed a pH of 6.82, carbon dioxide pressure (Pco) of
179 mm Hg, and oxygen pressure (Po-) of 143 mm Hg
with a base deficit of 14.3 mEq per liter. Within 30 min
utes the temperature had fallen to 103 F (39.4 C). Arterial
pH at this time was 6.96; Pco,, 88.8 mm Hg; and Po=, 134
mm Hg, with a base deficit 14.5 mEq per liter. A second
ampule of bicarbonate was given and 30 minutes later the
temperature was 97.2 F (36.2 C). The ice was removed
and the patient allowed to breathe room air. Arterial pH
was 7.32; Pco,., 30 mm Hg; and Po, 60 mm Hg, with a
base deficit of 10 mEq per liter. The BP had risen to
110/70 mm Hg without further vasopressors. At this time,
anesthesia had been off for IV2 hours. The patient was re
sponding slightly to painful stimuli, and the pupils were
small and reactive. One hour later pH was 7.32; Pco=, 27.3
mm Hg; and Po=, 54 mm Hg, with a base deficit 11 mEq
per liter, and an additional ampule of sodium bicarbonate
was given. The patient continued to improve, and by five
hours after peak temperature, he was responding to verbal
commands and moving all extremities. He was extubated
at this time with a temperature of 97.7 F (36.5 C) ; pH
7.33; Pco2, 31.4 mm Hg; and Po2, 63 mm Hg; the base
deficit was 8.2 mEq per liter. He continued to improve
throughout the night, during which time he received 3,000
cc 10% dextrose in water, with 130 mEq of sodium bi
carbonate. The following morning he was alert, without
neurologic deficit. Serum electrolyte studies reported in
mEq per liter revealed: Na, 135; Cl, 92; CO= combining
power, 26.7; and K 3.9. The postoperative course wa:j un
eventful.
CASE 2.-A 12-year-old, 69-pound (31.3 kg) girl was ad
mitted for adenoidectomy and myringotomy. Past history
revealed a generalized muscle weakness that had been
diagnosed as moderately severe myotonia congenita. The
patient's temperature the morning of surgery was 98.6 F
(37.0 C). After premedication with scopalamine hydro-
bromide, 0.2 mg, and meperidine hydrochloride, 30 mg,
anesthesia was induced with nitrous oxide and oxygen,
2:2 liters per minute, and halothane, 0.5%. Five minutes
after induction, chest compliance was noted to be markedly
decreased. Abdominal and jaw muscles were "stiff." Anes
thesia was discontinued, and the patient ventilated with
oxygen. Compliance increased to normal and it was de
cided to reanesthetize the child with ether, nitrous oxide,
and oxygen. Once again a marked fall in chest compliance
 109 surface of the body. If there is an absence of air
I06 movement (as might occur under surgical drapes),
TEMP. I03 then the surrounding quiet layer of air will become
(F) lOO saturated with water vapor and evaporation can no
97
94
longer occur. Similarly, if humidity in the operating
7.4
theater were inordinately high, then evaporative
7.2
heat loss would be diminished. Conduction involves
pH 7.0 the loss of heat from the body to surfaces in direct
6.8 contact with the body, as well as to the surrounding
180 layer of air. When these surfaces are warm, heat loss
Pco2 I40 by conduction cannot occur or is diminished.
IOO The processes of radiation and conduction account
(mm Hg) 60 for about 70% of heat loss in an individual in a nor
20 mal environment. Evaporation of water from the
BASE skin and lungs accounts for roughly 23% heat
DEFICIT
loss, while warming of inspired gases, and loss of
(mEq/L) heat in urine and feces is responsible for the rest.3
When the main avenues of heat loss (conduction
RINGERS
LACTATE 3000 cc and radiation) are blocked, then evaporation, which
NaHCOj normally accounts for less than 25% of the body's
(mEq/ 44 44 44 heat loss, must assume the predominant role in the
dissipation of heat. If this also is made inefficient,
then either heat production must decrease or body
HOURS OF ANESTHESIA
temperature will rise.
Temperature, arterial pH, Pco2, and base deficit of the One factor that can hinder heat loss is a warm
first case plotted against hours of anesthesia. The environment, which reduces the amount of heat
3,000 ml of Ringer's lactate were administered in ap loss by radiation to the environment. Operating
proximately 20 minutes.
room lights and poorly air-conditioned operation
rooms may produce an ambient temperature that
was noted after five minutes of anesthesia, which was approaches the patient's temperature.
again discontinued, and the child ventilated with oxygen. Among the factors that will decrease sweating
Five minutes later the child had a generalized seizure.
Temperature at this time was found to be 104 F (40.0 C), and evaporation are: (1) exocrine abnormalities, ie,
and within 15 minutes it rose to 108 F (42.2 C). Pupils congenital absence of sweat glands; (2) belladonna
were dilated and fixed. Alcohol sponging was ineffective drugs; and (3) surgical drapes. Sweating is also less
in lowering the temperature, and direct application of ice efficient in the short, stocky individual because of
was subsequently used. The temperature fell to 101 F
decreased surface area.
(38.3 C) in 45 minutes, at which time the ice was removed.
The temperature drifted down to 90 F (31.1 C), and she Several of these factors were present in our first
was warmed to 98 F (36.7 C). A tracheotomy was done. patient and probably contributed to his hyper
The patient remained comatose with dilated fixed pupils thermia. He was covered with drapes except for a
for the following five days at which time she died. An au small opening on the abdomen. This reduced heat
topsy revealed generalized polymyositis, bilateral broncho loss via evaporation and conduction. Evaporative
pneumonia, focal hepatic necrosis, diffuse anoxic enceph-
alopathy, and necrosis of the pituitary and hypothalamic heat loss was further inefficient because of the pa
area. tient's small surface area for his mass of tissue.
Comment Operating room lights produced heat.
Increased Heat Production.The following can
The maintenance of a normal body temperature cause heat production to increase: (1) endocrinop-
is dependent upon the balance between heat pro athies, such as thyrotoxicosis and pheochromo-
duction and heat loss. Whenever heat production is cytoma are associated with an increased metabolic
increased without a concomitant increase in heat rate; (2) increase in muscular activity which may
loss, the body temperature must rise. be present as shivering in response to cold, strug
Heat production is normally a reflection of the gling during induction of anesthesia, or during very
metabolic rate. In a normal individual (one without light anesthesiathe decreased compliance seen
excessive heat production or decreased heat loss) with certain anesthetics, such as mephridine, also
the metabolic rate maintains the body tempera represents increased muscular activity. (The de
ture at about 98.6 F (37.0 C). creased chest compliance seen in the second patient
Heat Loss.Loss of heat from the body occurs as represented increased muscular activity and was
a function of radiation, evaporation, and conduc probably responsible for the initiation of her hyper
tion. Radiation occurs when the surroundings im thermia.); (3) abnormality of the central tempera
pose less radiant energy than the patient emits. ture regulating mechanism in the hypothalamus,
Evaporative heat loss occurs when sweat is vapor specifically the anterior hypothalamus," can be asso
ized into surrounding air. It depends on relative ciated with hyperthermia. (The postmortem exami
humidity as well as movement of the air over the nation of our second case revealed diffuse necrosis

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 of the pituitary and hypothalamic areas.); and (4)
an elevated temperature which in itself results in
increased metabolism and heat production, and
can further elevate temperature and metabolism,
a factor that must be always considered in any pa
tient with a preoperative temperature elevation.
The presence of any or all of these factors can
lead to hyperthermia. Once a temperature increase
has occurred it may be self-perpetuating as it in
creases metabolism which further increases tem
perature. This vicious cycle can raise body tempera
ture to alarmingly high levels very rapidly. Recall
the 7 F (3.8 C) rise in 60 minutes in the first pa
tient and the 4 F (2.2 C) rise in 15 minutes tbat
occurred in the second patient. We would say that
a slight rise in temperature in an anesthetized pa
tient must be regarded as being potentially very
hazardous to the patient, and immediate attempts
should be made to find and correct the cause and
to prevent a further rise.
Physiologic disturbances that may result from
profound hyperthermia are acidosis, dehydration,
hypovolemia, hypotension, and hypoxia with ir
reversible tissue damage.
Acidosis can result from one of two sources.
First, with the marked increase in metabolism
(7% increase for 1 F rise in temperature,6 carbon
dioxide is produced at an increased rate. Ventilation
which is adequate for a normal metabolism is
grossly inadequate for an increased carbon dioxide
production and hence respiratory acidosis occurs.
Recall that in the first patient when the circulation
failed, the respirations likewise become depressed.
The marked rise in his Pco^ (180 mm Hg) was prob
ably a result of hypoventilation in combination with
increased metabolism.
Acidosis may also be secondary to tissue hy
poxia with elevated lactic acid resulting in a base
deficit. It would seem therefore that both metabolic
and respiratory acidosis may be present. Acidosis in
turn may produce hypotension through decreased
8
responsiveness to catacholamines.7 The hypoten
sion and associated fall in tissue perfusion probably
accentuate the tissue acidosis. Recall in our first
patient the profound hypotension (40 mm Hg)
that failed to respond to 5 mg of metaraminol in the
presence of an arterial pH of 6.82.
Hypovolemia occurs secondary to loss of fluid
via the skin and the lungs. This fluid which early in
the development of hyperthermia is almost isotonic5
(especially in an individual not heat acclimatized)
with extracellular fluid eventually becomes hypo-
osmotic. The resultant loss of this fluid results in a
decreased extracellular fluid volume and electrolyte
abnormalities.
Hypoxemia may result from several factors: (1)
shunting from atelectasis or opening of pulmonary
vascular channels that do not participate in gase
ous exchange; or (2) hypoventilation with de
creased intake of oxygen. Our first patient had a
low Po2 that probably represented a combination
of the above, ie, hypoventilation (Pco2, 180) and
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later shunting (Po2 of 60 on room air when the
Pco2 was 30). Hypoxia of the tissues is a result
of the low oxygen tension in the arterial blood
coupled with the decreased tissue perfusion.
We can see that the spectrum of hyperthermia
can be anything from a mild rise in temperature
without any adverse results to a hyperthermia with
profound hypotension, hypoxia, and irreversible
tissue damage or death.
Treatment
The primary consideration in the treatment of
hyperthermia involves reduction of the elevated
temperature as well as correction of all of the
physiologic abnormalities brought about during
the hyperthermic episode. These will be dealt with
separately.
Elevated Temperature.Prompt lowering of the
temperature is vital, and the method used depends
upon whether surgery is in progress or has been
completed. If the hyperthermia develops and the
abdomen is open, then efficient cooling can be
achieved by the installation of cold solutions into
the peritoneal cavity. The solution should prob
ably be isotonic to prevent tissue destruction and
we feel that lactated Ringer's solution is best.
Sodium chloride solution could also be used, but
may add slightly to the acidosis if absorbed. If the
surgical wounds are closed, then direct application
of ice is most efficient. If shivering is present, a
method to conteract it should be employed as this
increased muscular activity will tend to raise tem
perature. Small intravenous doses of chlorproma
zine hydrochloride or meperidine are useful in
preventing or decreasing shivering. Conversion from
a rebreathing to a nonrebreathing anesthetic system
increases heat loss from the lungs.
Acidosis.Accurate estimation of acidosis may
best be accomplished by determination of arterial
pH and PcoL. Both diagnosis and the determination
of effectiveness of therapy may be made with serial
determinations.
A rough estimate of the amount of base needed
is obtained by multiplying the base deficit times
0.3 times the patient's weight in kilograms.9 In
our first patient this would be 14.3 X 0.3 X 98.5
= 420
mEq. By giving only 44 mEq of sodium
bicarbonate at the beginning of the correction of
the acidosis we were certainly undertreating as evi
denced by the very small decrease in the base
deficit.
Respiratory acidosis is treated by hyperventila-
tion. Again, repeated arterial blood gas determina
tions are useful in following ventila tory adequacy.
A simpler and more rapid means of estimating
ventilatory adequacy requires the use of an end-
tidal C02 analyzer.
Hypoxia.Prevention of hypoxia requires ade
quate ventilation, preferably with an elevated per
centage of oxygen. If halotbane or cyclopropane or
ether alone are given with oxygen, the oxygen con
centration approaches 100% and the Po2 will prob-
 ably be adequate. If significant shunting has oc
curred, then the lowered percentage of oxygen
(25%) given with nitrous oxide could represent a
hypoxic mixture.
Increased Intracranial Pressure.li there is evi
dence of increased intracranial pressure after return
to a normal temperature, some means of lowering
this pressure might be considered. Intravenous ad
ministration of mannitol, urea, or hypertonic sodi
um chloride solution may be of help. One should
keep in mind, however, that a rebound increase in
cerebrospinal fluid pressure may occur following the
discontinuation of urea.10 Also, an osmotic diuresis
could further aggrevate the symptoms of hypo
volemia.
Hypovolemia.This is probably secondary to
large losses from the extracellular fluid space. Other
studies have failed to show an increased hematocrit5
as one would expect if the fluid loss were primarily
intravascular. The replacement fluid we have used
is Ringer's lactate. Large volumes administered
rapidly are given, and central venous pressure may
be monitored if one fears overloading the patient's
cardiovascular system. In the first case we infused
3,000 ml of Ringer's lactate in 20 minutes before
the BP returned to near normal values. Of course,
proportionately less would be used in a smaller indi
vidual.
Prevention
Prevention of hyperthermia depends primarily
upon the of the anesthesiologist. Any
awareness
patient exhibiting a preoperative temperature ele
vation should be carefully evaluated. If the pro
posed procedure is elective, then surgery should
be postponed until the temperature is normal and
the cause for the elevation is known. If the tempera
ture elevation is secondary to the disease process
for which the surgery is being done, eg, abcess, and
preoperative attempts to lower it have been un
successful, then after anesthesia has been induced,
direct cooling can be used along with antishivering
agents. In this case a nonrebreathing system along
with hydration, sparse drapes, etc, might prove to
be useful adjuvants. Belladonna drugs are best
avoided in the hyperthermic patient. Prevention also
involves recognition of hypermetabolic states and
proper temperature control of the operating room.
It is obvious that
one factor cannot be pointed
at being the cause of hyperthermia during anes
as
thesia. The infrequency with which it is seen must
mean that a combination of events occurring simul
taneously is required before a hyperthermic episode
can become manifest. Burford11 has said, "These
instances of severe hyperthermia probably represent
the unusual end result of a development which ordi
narily barely gets underway, or at best achieves
only moderate proportions."
It is probably not possible to predict which pa
tients will develop hyperthermia during surgery.
However, we can pay careful attention to the pre
disposing factors, and by doing so, decrease the fre-
qency and the severity with which these episodes
occur. Hyperthermia during anesthesia must be re
garded as a life-threatening condition that requires
both rapid and vigorous therapy if the patient is to
survive.
This study was supported in part by US Public Health Service
grants 5T1-GM-63-06, 5-K3-GM-17, and HE 07946-02.
Generic and Trade Names of Drugs
HalothaneFluothane.
Metaraminol bitartrateAramine Bitartrate.
PrednisoloneDelta Cortef, Hydeltra, Meticortelone,
Meti-Derm, Paracortol, Sterane, Sterolone.
ChlorpromazineThorazine.
MannitolMannitol.
References
1. Amer Soc Anesthesiol Newsletter, 26:21-22 (July) 1962.
2. Amer Soc Anesthesiol Newsletter, 26:30-31 (Aug) 1962.
3. Amer Soc Anesthesiol Newsletter, 26:10-11 (Nov) 162.
4. Bigler, J.A., and McQuiston, W.O.: Body Temperatures
During Anesthesia in Infants and Children, JAMA 146:551-556
(June 9) 1951.
5. Malamud, N.; Haymaker, W.; and Custer, R.P.: Heat Stroke;
Clinico-Pathologic Study of 125 Fetal Cases, Milit Surg 99:397-449
(Nov) 1946.
6. Guyton, A.C.: Textbook of Medical Physiology, Philadel-
phia: W.B. Saunders Co., 1956, pp 839-852.
7. Campbell, G.S., et al: Depressed Response to Intravenous
Sympathicomimetic Agents in Humans During Acidosis, Dis
Chest 33:18-22 (Jan) 1958.
8. Wood, W.B.; Manley, E.S., Jr.; and Woodbury, R.A.: Effects
of CO2-Induced Respiratory Acidosis on Depressor and Pressor
Components of the Dog's Blood Pressure Response to Epine-
phrine, J Pharmacol Exp Ther 139:238-247 (Feb) 1963.
9. Astrup, P.: New Approach to Acid-Base Metabolism, Clin
Chem 7:1-15 (Feb) 1961.
10. Rosomoff, H.L.: Distribution of Intracranial Contents After
Hypertonic Urea, J Neurosurg 19:859-864 (Oct) 1962.
11. Burford, G.E.: Hyperthermia Following Anesthesia; Con-
sideration of Control of Body Temperature During Anesthesia,
Anesthesiology 1:208-215 (Sept) 1940.

LEVEL IN SEVERAL DISEASES.-The concentration

CAERULOPLASMIN
of caeruloplasmin is low in the serum of patients with Wilson's disease
(Scheinberg and Gitlin 1952), and it has been suggested that this is the most
typical single biochemical abnormality of the condition (Beam and Kunkel 1954).
There are, however, other diseases in which the serum concentration of caerulo
plasmin may fall temporarilyfor instance, the malabsoiption syndrome, kwashi-
orkor, protein-losing enteropathy, scleroderma involving the small gut, the nephrotic
syndrome, and hypoproteinaemia in the neonatal period and in infancy (Sternlieb
and Scheinberg 1961)but none of these conditions is likely to cause diagnostic
confusion with Wilson's disease.Walshe, J. M., and Briggs, J.: Caeruloplasmin in
Liver Disease, Lancet 2:263 (Aug. 11) 1962.

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