Post-Op Fevers and Cognitive Decline
DURHAM, N.C. -- While physicians have long noticed and
written off the fact that many patients develop fever shortly
after coronary bypass surgery, a new Duke University Medical
Center study shows that these fevers are associated with
measurable cognitive decline six weeks following surgery.
Specifically, the researchers found a relationship between
the maximum postoperative temperature experienced by the
patient during the first 24 hours in the intensive care unit
and significant cognitive decline, as measured by a standard
battery of cognitive and psychological tests administered
before and after surgery. Thirty-nine percent of the patients
in their study were found to have cognitive deficits six weeks
after bypass surgery.
Such elevated temperatures, a condition known as
hyperthermia, are common after bypass surgery and have
traditionally been seen more as a nuisance than a pressing
medical issue, said the Duke researchers. For that reason,
early post-operative hyperthermia has not received serious
scientific study, they said.
The study was published today (Feb. 1, 2002) in the journal
Stroke. The research was supported by grants from the National
Institutes of Health.
"This is the first study to look at early post-operative
hyperthermia, and it shows a clear association between this
hyperthermia and cognitive decline," said Dr. Hilary Grocott,
associate professor of anesthesiology and lead investigator of
the Duke study.
"While this study does not answer the question of whether
the cognitive decline develops as a result of the hyperthermia,
or whether the cognitive decline and the hyperthermia are
caused by the same underlying process, the association is
definitely there," he continued. "Clearly, this is a common
phenomenon, and one in which we could potentially intervene to
improve the cerebral outcome of heart surgery patients."
While many patients undergoing any type of surgery develop
some degree of hyperthermia within one to three days of
surgery, Grocott said that bypass patients tend to develop
elevated temperatures much sooner ? within eight to 10 hours
after surgery. While the exact cause of this hyperthermia is
not clearly understood, the body's inflammatory response to
surgery itself, which is particularly pronounced following
bypass surgery, is likely involved, he said.
To determine whether this phenomenon has any negative
impacts on a patient's cognitive function after surgery, the
Duke team studied 300 patients who were to undergo coronary
artery bypass procedures.
The day before surgery, patients took a battery of
standardized tests. Immediately after surgery, body
temperatures were taken hourly for 24 hours while the patients
recovered in the intensive care unit. Patients took the same
battery of standardized tests six weeks later.
"During that 24-hour period, maximum temperatures ranged
from 37.2 degrees Celsius (98.9 F) to 39.3 degrees Celsius
(102.7 F), and we found that those patients who had the greater
post-operative hyperthermia also had the higher rates of
cognitive dysfunction," Grocott said.
"It appears that heart surgery can cause brain injury in
some patients, which makes the brain susceptible to further
damage caused by hyperthermia," Grocott said. "For example, a
normal healthy brain likely would not show negative effects
from a temperature of 39.3 degrees Celsius; however, elevated
temperatures can cause further damage to an already-injured
Earlier Duke studies have demonstrated that up to 42 percent
of heart surgery patients suffer measurable cognitive decline
five years after surgery and, while researchers do not totally
understand the mechanism behind this phenomenon, one
explanation is that during the operation, tiny bits of plaque
break off from clogged arteries, travel to the brain and starve
brain cells of oxygen, a condition known as ischemia.
"We know from many experimental models that, if an ischemic
brain is injured in some way, temperatures above 37 degrees
Celsius (98.6 F) can cause further damage," Grocott explained.
"High temperatures make a bad situation even worse, and that is
why strategies that keep the brain cool could protect brain
cells, and we would hypothesize that this would provide some
protection against cognitive decline."
It appears that high temperatures cause the brain to release
excitatory neurotransmitters in higher than normal amounts,
further damaging susceptible brain cells. Other research has
demonstrated that in response to restored blood flow, ischemic
brain cells release elevated quantities of potentially
destructive oxygen free radicals.
It is likely, Grocott explained, that there are many factors
that contribute to cognitive decline in heart surgery, and the
Duke team is investigating different strategies to protect the
the possibility of actively cooling the body postoperatively
in order to counteract this hyperthermic tendency.
These strategies also include using minimally invasive
surgical techniques, which means that the heart-lung machine is
not needed. The researchers have also found a genetic component
to the decline.
Patients with the E-4 variant of the APOE gene (which has
also been linked to early onset Alzheimer's disease) tend to do
worse than patients with other variants of the gene.
Joining Grocott in the study were current and former Duke
colleagues Dr. G. Burkhard Mackensen, Dr Alina Grogore, Dr.
Joseph Mathew, Dr. Jerry Reves, Dr. Barbara Phillips-Bute, Dr.
Peter Smith and Dr. Mark Newman as well as other members of the
Neurologic Outcomes Research Group (NORG) and the
Cardiothoracic Anesthesia Research Endeavors (CARE) research
teams of the Duke Heart Center.
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