Fever
Normal body temperature is neither set nor maintained by circulating
factors. In contrast, fever results when endogenous pyrogens increase the thermoregulatory
target temperature ("set point"). Identified endogenous pyrogens include interleukin-1,
tumor necrosis factor, interferon-α, and macrophage inflammatory protein-1.
[194]
Although it was initially believed that these
factors acted directly on hypothalamic thermoregulatory centers,[195]
there is increasing evidence for a more complicated system involving vagal afferents.
[196]
Most endogenous pyrogens have peripheral
actions
(e.g., immune system activation) in addition to their central generating capabilities.
Fever is relatively rare during general anesthesia when one considers
how often febrile stimuli are likely to be present. It is rare because volatile
anesthetics per se inhibit the expression of fever ( Fig.
40-24
),[197]
as do opioids.[198]
Infection is by far the most common cause of fever. Such fever may reflect preexisting
infection or result, for
Figure 40-24
Change in core temperature after the administration of
50,000 IU/kg of interleukin-2 (IL-2) followed by a second dose of 100,000 IU/kg 2
hours later. The first dose of IL-2 defined elapsed time zero; anesthesia was started
after 3 elapsed hours and continued for 5 hours. Data are presented as means ±
SD. MAC, minimum alveolar concentration. (Redrawn from Negishi C, Lenhardt
R, Sessler DI, et al: Desflurane reduces the febrile response to interleukin-2 administration.
Anesthesiology 88:1162–1169, 1998.)
example, from urologic manipulations. However, perioperative fever also occurs in
response to mismatched blood transfusions, blood in the fourth cerebral ventricle,
and allergic reactions.[199]
In addition, some
degree of fever is typical after surgery.[200]
The causes of fever are sufficiently diverse—and potentially serious—that
a search for a specific etiology is usually warranted.
Treatment of hyperthermia depends on the etiology, with the critical
distinction being between fever and the other causes of hyperthermia. (In general,
patients with fever and increasing core temperature will have constricted fingertips,
whereas those with other types of hyperthermia will be vasodilated.) It is always
appropriate to treat the underlying causes, but nonfebrile hyperthermia will also
improve with cooling. The first- and second-line treatments of fever are amelioration
of the underlying cause and administration of antipyretic medications. The first
treatment strategy often fails because the etiology of fever remains unknown; alternatively,
the source may be known but unresponsive. The second strategy also often fails or
is only partially effective, perhaps because some fever is mediated by mechanisms
that bypass conventional antipyretics.[194]
It
is in these patients that third-line treatment is most likely to be implemented:
active cooling. Active cooling of febrile patients is intuitive. However, it often
fails to reduce core temperature—while simultaneously worsening the situation
by triggering thermoregulatory defenses, including intense discomfort, shivering,
and activation of the autonomic nervous system.[201]
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