Public Release: 

Fever immediately after heart bypass surgery associated with cognitive decline

Duke University Medical Center

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 brain."

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 brain, including 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.

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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.

Note to editors: Dr. Hilary Grocott can be reached at 919-681-5024 or at h.grocott@duke.edu.

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