HYPOTHERMIA AND HYPERTHERMIA

Yoram Shapira, Akiva Leibowitz, Evgeni Brotfain

323

Overview
Humans are euthermic beings, that is, critical physiologic functions must
e bemaintained within a fixed temperature range. Any shifts from a body
coretemperature of 36.6°C ± O.2°C results in either hyperthermia or hvpo-
thermia,causing pathophysiologic reactions. Normal thermoregulation is a
hlghlycomplex positive and negative feedback system depending on input
andfeedback from nearly every tissue ofthe body, and several well-identifi-
edresponse mechanisms. While the hypothalamus and skin are identified as
havlngthe major role in thermal regulation, nearly every tissue of the body
,sinvolved in the process. More frequently, intraoperative thermal dysregu-
~tion results in hypothermia. However, when hyperthermia occurs it must
alsabe quickly addressed, particularly in patients with neurological injury
ordisease.

Processingof thermoregulatory information occurs in three phases:

Afferent input: Temperature sensitive cells fire in response to excessive
coldand heat. Information is transmitted in distinct neural fibers via multi-
plespinaltracts to the hypothalamus where it is then processed.
Central control: Most of the processing takes place in the hypothalamus,
whereinput from different sites is compared and integrated, and responses
areregulated when deviation from threshold appears. Many factors influen-
cetheabsolute threshold and normal core temperatures in humans. Distin-
9U1Shingnormal deviations from pathological states is of major importance.
fhe Inter-threshold range is a range bounded by sweating on the upper end
'odshivering on the lower end where perturbations of O.2°C frorn threshold
Qorot typically trigger an autonomie response.

iVO fiii'
lIoara 20 II
 Efferent response: Thermal perturbations rrom normal limits activatt
effector responses that increase metabolic heat production or alter environ_
mental heat loss. Eaeh thermoregulatory effector has its own threshold and
gain, so there is an orderly progression of responses and response intensities
In proportion to need. Aside from autonomie responses, behavioral respon_
ses play an important role, and the lack of this response in anesthetized
patients should be taken into account

Complications of perioperative hypothermia

Perianesthetic hypothermia produces potentially severe complications.
The controversial benefits of mild hypothermia in the neurosurgical setting
324
will be discussed further below.

Wound infection and healing

Wound infection and impairment of healing are among the most common
serious complications of anesthesia and surgery, known to increase morbidi-
ty and lengthen hospital stay.
\i

Coagulation m
Coagulation is impaired in hypothermic patients and is thought to be ma- m
inlya result of a decrease in activity of elot activating factors, Other rnecha-
nisms shown to be impaired include platelet function and the fibrinolytic
system.

Two points should be kept in mind:

- platelet count is not affected;
- routine coagulation studies will usually result in normal coagulation
function, as these tests are performed routinely in an environment of
3rc.
Adverse myocardial events
Mild hypothermia has been shown to increase the risk three-fold of post-
operative adverse myocardial events. Particular care should be taken with
patients suffering from preexisting cardiac ischemic disease, and elderly pa-
tients.

Drug metabolism
Drug metabolism is decreased by perioperative hypothermia, and postan-
esthetic recovery 15 prolonged. The effect of hypothermia differs from drug
to drug, and IS listed in Table 1.

A c ( un litătl ] 1111(111;1'';
lInii III Allcstezit' şi Trrnp,e. '
 !,ble 1. Effect of hypotllermio on d
rug mNobolism

ţ"'"
:Nluromuscular blocking
Eff~ct

Mainly pllarmaeokinetic ff
:aglnts Prolonged duration Reeo~eect. Onset of Detion delaYCd.
um affected more th At ry mlnlmally affceted. Vceuroni-
ne not altered. an racunum. Effieacy of Neostlgml-

~nhalld anesthetics
~~~:~c~~y~amie effect. Solubility inereases. Oecrease in
o ar everv 'c,

Propofol
lncrease in plasma eoncentration of 30% when temperat _
re decreased by 3'c. u

Postoperative shivering 325

Patients report shivering .and thermal discomfort as their worst experien-
ceof the perioperative period, even worse than surgical pain. Of particular
nterest in neurosurgery - shivering increases ICP and intraocular pressure,
In addition to stretching surgical incisions, and interrupting monitoring de-
Ilces.lncidence is as high as 400f0, but decreases when patients are kept nor-
nothermic and larger doses of opoids are used intraoperatively. Shivering
'l1ay increase metabolic rate and oxygen consumption by 2000f0.

The approach to postoperative shivering should include:

- skin surface warming: Shivering threshold is dependent on core and
mean skin temperature. Thus, aside from heating, this augments cuta-
neous warm input, allowing more core hypothermia, decreasing the shi-
vering threshold. Skin warmers increase mean skin temperature by only
a few degrees, thus it is important to raise core temperature > 35°C, for
augmentation of warm input to be efficient and to prevent shivering.
- drugs: Meperidine (25-75 mg IV) is considerably more effective in trea-
ling shivering than equianalgesic doses of other u-aqonists, and this
may be attributed to its effect on p receptors. Clonidine (75-150 jl9 IV,
most probably by reducing vasoconstriction and shivering thresholds),
Ketanserin (10 mg IV), Tramadol (1-2 mg/kg), Physostigmine (0.04 mg/
kg), Magnesium Sulfate (30 mg/kg).

Theropeutichypothermia in neuroanesthesia
The decrease in metabolic rate and oxygen demand has led researchers
indclinicians to postulate that hypothermia might .have bene~cial effects
0fIneurological outcomes, in a vast array of Situa tions invotvinq cerebral
r.cherniaand brain trauma. While numerous studies have shown rnild hypo-

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 thermia to provine protccuon aqainst cerebral ischcmm and hypoxemia in
an if118I species, thc only bcnefit uncqulvocallv proven in humans ls on Ihe
neurclcqical outcorncs following cardiac arrcst / vcntricular fibrillalion.

Gtooal tscuemio
Severa: studies have shown improved neurological outcome and reduc~d
mortality in cornatose survivors after cardiac arrest treated with mild hvpo-
thermia (32'C-34'C) for a period of 12 - 72 hours.

Intracranial aneurysms
Human control led studies have not shown clear-cut beneficial effects of hy-
326 pothermia. A number of studies show some possible benefit of hypothermia as
a last resort treatment for carefully selected subgroups of patients suffering
cerebro-vascular spasm (CVS)following subarachnoid hemorrhage (SAH).Ne-
vertheless - complications are often severe and should be closely monitored.

Traumatic brain injury

Hypothermia as a protective mecharusrn in traumatic brain injury is under
debate. It has been shown to decrease ICP. Some studies have been able
to show sorne benefit In particular subgroups of the study. Recent inves-
tigations show no overall beneficiat effect of hypothermia on outcornes of
traumatic brain injury. When a decision to induce hypothermia does occur
- severa! factors must be taken into consideration:
- opposing thermoregulatory responses ta hypothermia: This means pro-
viding anesthesia /sedation and preventing shivering.
- cooling techniques: There is wide variety of techniques, invasive and
non-invasive. The most appropriate technique should be selected.
- rewarming: There is no consensus an the ideal time ar rate for rewar-
ming patients. Common practice is O,S"C-1'C / hour. When hypothermia
is prolonged, rewarming may be as gradual as 1·C/day.

Key points:
Shifts from a body core tcmperature of 36.6·C ± 0.2'C results in hypert-
hermia ar hypothermia, causing pathophysiologic reactions, setting off a
vanetv of response mechanisms. General anesthesia irnpairs normal regula-
tion siqnificantlv.
Effector mechanisms preventing hypothermia Include: Vasoconstriction,
Shivering, and Non-shivering thermogenesis.
Factors contributing ta hypothermia which may be modified include: aR
ambient temperature, drugs, exposure and duration.
 Core body temperatur .
. e monltorin .
I'Ihen monltored in one of 5' 9 ISextremely .
h sltes - p 1 Important a d' .
SOP arynx, tympanic memb u monary artery di .an ISrehabie
Intervention in three ph rane and bladder. ' Istal esophagus, na-
ling
di '. ases of hy h .
. re istributinn hypoth ermla. Ph pot ermla is cru era. l:. Phase 1 ".
atlon or convection. Phase 3 . ase 2 - minimizing h ti - mmlml-
in the vasoconstriction phas - monltoring and preventi~~ ~s~due to rad!-
Passive insulation d ~. o yperthermla
an active w .
normothermia.
. . armlng are the mainstay of mamtamlng
. '.
Penoperatlve hypothermia
be avoi causes a variety f .
shouId .e avoided.
.
Evidence a d vocatinq. pe o. systemlC
. complication s and
surgery IS lirnited. rrnrssive hypothermia in neuro-
Meperidine is the Opiate of choirce f or treatment of st 327
po -operative shivering.
Overview: Hyperthermia
Even a mild elevation in brain ternpe t .
hypoxic, ischemie and injured brain Hyperathure may be detnmental to the
. . . . . r ermlC states may be causedb
wldevarietv of clinical disorders which are divid d l . ya
1) Control led hyperthermia _ resulting from ~ ~e l~ttOtwofmhaJorgroups:
. via Ion o t ermoregula-
tory set points and thresholds,
2) Uncontrolled hyperth~rmia - resulting from impaired thermoregulato-
ry responses or excessive heat production. Table 6 lists major causesof
hyperthermia.

Numerous studies have found pyrexia to be associated with increased

mortality and morbidity after stroke. Early fever is associated with a poor
Glasgow Coma Scale score in traumatic brain injury patients. Patients with
subarachnoid hemorrhage are at increased risk for cerebral ischemia due to
vasospasm.Hyperthermia may potentially worsen this vasospasm mediated
brain injury. Several studies have shown hyperpyrexia to be an independent
riskfactor, predicting worse outcornes in T81,SAH and ischemia. Blood in the
cerebrospinal fluid induces fever in experimental models, and temperature 15
thusa likely marker for the primary severity of the hemorrhage.
Ihe major damage of hyperthermia is a result of direct cellular toxicr-
ty,i.e. deterioration of mitochondrial activity and, alterations of enzymatlc
reactions and cell membrane instability. Cellular effects rnav progress to
I'Ildespread organ pathophysiologic reactions.
Muscle damage, degeneration, and necrosis are direct results of extre-
meheat production and are associated with significant elevation In muscle
enzymes.Cardiovascular effects caused by elevated core bodv temperature

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 are associated wilh high cardiac output due to an mcrcase In dcmand a d
diminished pcripheral vascular resistance (sccondary to vasodilation a~d
dehydration). and tachvarrhvthmias (sinus tachvcardia, and also VTNF)svr
Hiqh-output cardiac Iailure and heat-induced myocardial damagc ofte~
lead to various degrees of systemic hypotension.
Table 2. Major causes of hyperlhermia d

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CBF and CMR are increased by elevated body temperature (between 37'C
and 42·C). but above 42·C cerebral oxygen consumption decreases due to
cellular enzymatic degradation. Uncoupling of CNS metabolism may lead
ta further damage if CBF is compromlsed, and may have deleterious effects
an the non compliant brain by raising ICP. Other effects of hyperthermla
an the injured and ischemie brain include: direct brain and spinal cord te-
xrcitv associated with cell death, alterations in membrane stabilitv, enzyme
function and neurotransmitter release, BBB disruption, cerebral ederna and
local hemorrhage. epileptic activity and increased peritumoral edema. These
processes may lead to profound stupor, coma and seizures.
In conscious patients - ataxia, dvsmetna and dvsarthria mav be seen. CSF
analysis may reveal increased protein levels, xanthochromia and Slightly
elevated Iymphocyte count. Any underlying pathological condition of the

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central nervous system (traumatic brain inj'ury isch .
)
hemorrhage may b e adversely affected by hyperth' ' emlc strokc ' intracranial
..
mes b . . hyperthermia and ermla,
co may e worse. Coexlstlng irn . and
d bcllnlcal
. out-
atlOn
. . b . " . palre raln autore-
gul In raln-Injury rnav put pntlents at risk for cerebral hypoperfusion
dunng pericds of low blood presSure, whereas they may be prone to the
developm.ent of vasog~nic ed~ma, vascoia- engorgement, and worsening of
intracranlal hvpertenslnr, dunng penods of high blood pressure.
Hyperthermic reactions may cause acute renal failure (incidence SOfa) se-
condary to dehydration, hypotension and muscle damage. Acute tubular
necrosis with moderate proteinuria is more common. In the gastrolntestinal
tract, hyperthermia frequently leads to ischemie uleerations that may result
In bleeding, elevated liver enzymes, cholestasis and hepatic necrosis. 329
White blood cell count is frequently elevated in hyperthermic patients. In
cases of fatal hyperthermia DIC may evolve, leading to bleeding diathesis
and multiple organ failure. Laboratory blood tests will reveal hyperglyce-
elevated serurn cortisol. and elevated growth hormone and aldoste-
mia,
rone levels. Eleetrolyte disorders include decreased serurn potassi
assrum, miild
hypophosphatemia and hypocalcemia. Pulmonary thermal injurv may cause
cor-pulmonale and ARDS Pulmonary edema ISalso common.

Table 3. Clinical and laboratory monifestottons o f h y perthermia

Clinical manifestations:

Cardiovascular effects Tachyarrhythmia. various degree of systemie

hypotension

Ataxia, dysmetria, dysarthria, profound

Neurologic effects
stupor, coma and seuures

Pulmonary edema, ARDS

Respiratory
Acute tubular necrosis, renal failure
Renal failure
Degeneration and neerosis, rhabdOmyolYSiS:-
Muscle
.
Bleeding, elevated liver enzyme s, cholestasls
Gastrointestinal
and hepatic necrOSIS -

Laboratory tests: -
White blood cell count
Elcvatcd -
Coagulation DIC . I -
.levaled serum cortlso,
Electrolytes, chemistry, hormones Hyperglyccmla, e d aldosteronc levels
growth Ilormone an o hosphatemla, and
Hypokalemia, miid hyp P
hypocalcemla
,--
TI m'şoara 20i I
 Prevention - Hyperthermia
Core body ternperature should be measured continuously throughout the
entire perioperative period. Core ternperature is best reflected by measure_
ments in five sites: tvrnpanic membrane, pulmonary arterv, distal esophagus,
nasopharynx, and bladder. Rectal temperature tends to lag behind core body
temperature.
instances of "controlled" fever. Some evidente exists, demonstrating ac-
vantages in pharmacolcqic control of hyperpyrexia in brain injured patients.
Nevertheless, the benefits of pharrnacoloqic antipyretic therapy, compared
with associated risks, have not been clearlv established.

330
Key Points
Hyperthermia is caused by a variety of clinical states. It is important to
differentiate controlled and uncontrolled hyperthermia and evaluate the
underlying cause.
Continuous temperature monitoring is essential, and mav be an indicator
of a life threatening syndrome.
Ma lig nant hyperthermia is life threatening and should be treated promptly.
Elevated core temperature lags behind other signs and symptoms. When
suspected, discontinue causative agents, treat with IV Dantrolene, cool pa-
tient and provide support.
Surgical intraoperative causes of hyperthermia include: acute hydroce-
phalus, fourth ventricle bleeding, hypothalamic insult, and intracerebral
bleeding.
Treatment depends on etiology, and includes active cooling and phar-
macologic antipyretic therapy, and is warranted particularly in the injured
brain.

ActuallttJfl 'n An~strz;e şi T~ropit fnltflSl'l

Suggesled readlng - Hypothcrmia

1.Hutehison JS, Ward RE, Laeroix J, Hebert PC B

tesrnan R, Joffe AR, KirpJlani HM M' ,arnes MA, BOhn DJ, Dlrks PB D .
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Suggested reading - Hyperthermia

J,CarrnsCJ, Andrews PJ: Management of hyperthermia in traurnatic brain injury. Curr Opin Crit Care 2002;
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1.Cormio M, Citerio G, Portella G, Patruno A, Pesenti A: Ireatrnent of tever in neurosurgical patients.
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M: Thermoregulatory responses ro hyperthermia during isoflurane anesthesia