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From the Cerebral Vascular Disease Research Center, Department of
Neurology, University of Miami School of Medicine (Fla).
Background—Moderate elevations of
brain temperature, when present during or after ischemia or
trauma, may markedly worsen the resulting injury. We review these
provocative findings, which form the rationale for our
recommendation that physicians treating acute cerebral ischemia
or traumatic brain injury diligently monitor their patients for
incipient fever and take prompt measures to maintain core-body
temperature at normothermic levels.
Summary of Review—In standardized models of transient forebrain
ischemia, intraischemic brain temperature elevations to
39°C enhance and accelerate severe neuropathological alterations in
vulnerable brain regions and induce damage to structures not ordinarily
affected. Conversely, the blunting of even mild spontaneous
postischemic hyperthermia confers neuroprotection. Mild
hyperthermia is also deleterious in focal ischemia,
particularly in reversible vascular occlusion. The action of otherwise
neuroprotective drugs in ischemia may be nullified by mild
hyperthermia. Even when delayed by 24 hours after an acute insult,
moderate hyperthermia can still worsen the pathological and
neurobehavioral outcome. Hyperthermia acts through several mechanisms
to worsen cerebral ischemia. These include (1) enhanced release
of neurotransmitters; (2) exaggerated oxygen radical
production; (3) more extensive blood-brain barrier breakdown;
(4) increased numbers of potentially damaging ischemic
depolarizations in the focal ischemic penumbra; (5) impaired
recovery of energy metabolism and enhanced inhibition of
protein kinases; and (6) worsening of cytoskeletal proteolysis. Recent
studies demonstrate the feasibility of direct brain temperature
monitoring in patients with traumatic and ischemic injury.
Moderate to severe brain temperature elevations, exceeding core-body
temperature, may occur in the injured brain. Cerebral hyperthermia also
occurs during rewarming after hypothermic cardiopulmonary
bypass procedures. Several studies have now shown that elevated
temperature is associated with poor outcome in patients with acute
stroke. Finally, recent clinical trials in severe closed head injury
have shown a beneficial effect of moderate therapeutic hypothermia.
Conclusions—The acutely ischemic or traumatized
brain is inordinately susceptible to the damaging influence of even
modest brain temperature elevations. While controlled clinical
investigations will be required to establish the therapeutic efficacy
and safety of frank hypothermia in patients with acute stroke, the
available evidence is sufficiently compelling to justify the
recommendation, at this time, that fever be combated assiduously in
acute stroke and trauma patients, even if "minor" in degree and
even when delayed in onset. We suggest that body temperature be
maintained in a safe normothermic range (eg,
36.7°C to 37.0°C [98.0°F to 98.6°F]) for at least the first
several days after acute stroke or head injury.
© 1998 American Heart Association, Inc.
Comments, Opinions, and Reviews
Combating Hyperthermia in Acute Stroke
A Significant Clinical Concern
Key Words: fever • ischemia • hypothermia • neuroprotection
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